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  • CLASSES

    Ketolide Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    A broad-spectrum ketolide antibiotic; exhibits more potent antibacterial killing than macrolides; studied in multiple respiratory tract infections; spectrum of activity good against respiratory pathogens, including erythromycin- and penicillin-resistant pneumococci and intracellular and atypical bacteria. Once-daily dosage is as effective as clarithromycin, trovafloxacin, and high dose amoxicillin for some infections.

    COMMON BRAND NAMES

    Ketek

    HOW SUPPLIED

    Ketek Oral Tab: 300mg, 400mg

    DOSAGE & INDICATIONS

    For the treatment of mild or moderate community-acquired pneumonia (CAP).
    Oral dosage
    Adults

    800 mg PO once daily for 7 to 10 days.

    MAXIMUM DOSAGE

    Adults

    800 mg/day PO.

    Elderly

    800 mg/day PO.

    Adolescents

    Use not recommended.

    Children

    Use not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is necessary for patients with hepatic impairment without concurrent renal impairment. Moderate to severe hepatic impairment (mean Child Pugh of 9.2) results in a 1.4-fold higher terminal elimination half-life. Decreased hepatic clearance is partially compensated by increased renal clearance.

    Renal Impairment

    CrCl >= 30 ml/min: No dosage adjustment is necessary.
    CrCl < 30 ml/min: Reduce dose to 600 mg PO once daily.
    CrCl < 30 ml/min and coexisting hepatic impairment: Reduce dose to 400 mg PO once daily.
    Intermittent hemodialysis
    Reduce dose to 600 mg PO once daily. On hemodialysis days, give dose after the hemodialysis session.

    ADMINISTRATION

     
    NOTE: A FDA-approved MedGuide is available for this medication. Dispense the appropriate MedGuide to the patient with each prescription and refill.

    Oral Administration

    May administer orally without regard to meals. Food does not affect the bioavailability of telithromycin.
    Do not chew or crush. Swallow the tablet whole.

    STORAGE

    Ketek:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    The concurrent use of telithromycin with simvastatin, lovastatin, or atorvastatin should be avoided. Telithromycin increases simvastatin concentrations due to CYP3A4 inhibition. A similar interaction may occur with atorvastatin and lovastatin which are also CYP3A4 substrates. Increased serum concentrations of HMG-CoA reductase inhibitors are associated with myopathy. As recommended by the manufacturer, therapy with simvastatin, lovastatin, or atorvastatin should be suspended while taking telithromycin. There are no known adverse effects with short-term discontinuation of statins.

    Macrolide hypersensitivity

    Telithromycin is contraindicated in patients with a history of hypersensitivity to telithromycin and/or any component of the commercial formulation. Although telithromycin is a ketolide antibiotic, it does have a similar structure to the macrolide antibiotics. Patients who have shown macrolide hypersensitivity should not be given telithromycin because there may be a risk of cross sensitivity with other macrolide antibiotics.

    Viral infection

    This drug does not treat viral infection (e.g., common cold). Prescribing telithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier. Antibiotic therapy can result in superinfection with non susceptible organisms. Overgrowth of Candida can occur with telithromycin therapy. Patients should be monitored closely during therapy.

    Alcoholism, hepatic disease, hepatitis, jaundice, renal failure, renal impairment

    Telithromycin is contraindicated in patients with a previous history of hepatitis and/or jaundice associated with the use of telithromycin or any macrolide antibiotic. Telithromycin should be used with caution in patients with hepatic disease. Hepatic dysfunction, including elevated hepatic enzymes and hepatitis, with or without jaundice, has been reported with the use of telithromycin. These events were generally reversible. Use cautiously in patients with a previous history of hepatitis/jaundice associated with the use of telithromycin. Post-marketing, three cases of hepatic failure have been reported ; one patient recovered, another required liver transplantation, and the third died. A history of alcohol use was noted in two patients, the one requiring transplantation and the one who died. Additional post-marketing cases of hepatic reactions have been reported. These reactions occur during or immediately after treatment with telithromycin. In some of these cases, liver injury progressed rapidly and occurred after administration of a few doses. Therefore, telithromycin should be used cautiously in patients with a history of alcoholism since they may be at increased risk of hepatoxicity from telithromycin. Patients should be monitored for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly. If signs or symptoms of hepatitis occur, telithromycin must be discontinued and medical evaluation undertaken, which includes liver function tests. If clinical hepatitis or transaminase elevations combined with other systemic symptoms occur, telithromycin should be permanently discontinued. Further, hepatic metabolism and terminal elimination half-life of telithromycin is reduced in patients with hepatic disease. Since elimination of the drug is via the liver and the kidneys, reduced hepatic metabolism may be offset by increased renal excretion. Dose reductions are not recommended for patients with hepatic impairment alone; however, for those patients with severe renal impairment (CrCl less than 30 mL/minute) or renal failure, the dose must be reduced. Telithromycin is a competitive inhibitor of hepatic CYP3A4 and should not be administered with certain drugs. Concurrent administration of telithromycin with cisapride and pimozide is contraindicated. In addition, in patients with renal or hepatic impairment, concurrent use with colchicine is contraindicated.

    Pregnancy

    Telithromycin is classified in FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. Teratogenic effects have not been identified in rats and rabbits with telithromycin administration. Telithromycin should not be used during pregnancy unless clearly indicated.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Telithromycin can prolong the QT interval in some patients which may lead to an increased risk for fatal ventricular arrhythmias, including ventricular tachycardia and torsade de pointes. Post-marketing reports have included cases of syncope (associated with vagal syndrome), ischemic cardiac events (associated with hypersensitivity reactions), palpitations, as well as atrial and ventricular arrhythmias (i.e., ventricular tachycardia, torsades de pointes). In some cases, ventricular arrhythmias occurred within a few hours of the initial dose. Avoid telithromycin use in patients with: congenital long QT syndrome; ongoing proarrhythmic conditions such as uncorrected electrolyte imbalance (e.g., hypokalemia, hypomagnesemia, hypocalcemia); clinically significant bradycardia; and cardiac arrhythmias who are receiving Class IA (e.g., procainamide, quinidine) or Class III (e.g., dofetilide) antiarrhythmic agents. Use telithromycin with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including telithromycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Breast-feeding

    It is not known whether telithromycin is excreted in human breast milk. The manufacturer recommends that it should be used cautiously during breast-feeding. Telithromycin, a ketolide, is structurally similar to the macrolide antibiotics. A prospective observational study assessing the safety of macrolide antibiotics during lactation found that 12.7% (n = 55) of babies exposed to macrolides via breast milk experienced adverse events including rash, diarrhea, loss of appetite, and somnolence. The adverse event rate was similar to that seen in babies in a control group whose mothers were treated with amoxicillin (8.3%). A population based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3 to 3 times more likely to have been exposed to a macrolide antibiotic through breast milk during the first 90 days of life than babies not exposed during that same time period. The study did not specify which antibiotic the mothers of affected babies were prescribed; however, the majority of macrolide prescriptions were for erythromycin (72%), with 7% for azithromycin and 1.7% for clarithromycin. The American Academy of Pediatrics (AAP) considers erythromycin to be a medication that is usually compatible with breast-feeding; azithromycin and clarithromycin have not been evaluated by the AAP. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children, infants, neonates

    The safe and effective use of telithromycin in neonates, infants, children and adolescents younger than 18 years of age has not been established.

    Geriatric

    In clinical trials, (n = 4780), telithromycin was administered to 694 geriatric patients (65 years and older), including 231 patients 75 years and older. Safety and efficacy in elderly patients were similar to that observed in younger patients. However, greater sensitivity of some older patients cannot be ruled out. No dosage adjustment is required based on age alone. Geriatric patients may be at increased risk for developing a prolonged QT interval when using telithromycin. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Myasthenia gravis

    Telithromycin is contraindicated in patients with myasthenia gravis. Exacerbations of myasthenia gravis have been reported in patients with myasthenia gravis treated with telithromycin. This has sometimes occurred within a few hours after the first dose of telithromycin. Reports have included death and life-threatening acute respiratory failure with a rapid onset in patients with myasthenia gravis treated for respiratory tract infections with telithromycin. Telithromycin is a treatment of last resort in such patients; close monitoring is necessary. Advise patients to discontinue therapy and seek medical attention if they experience an exacerbation of symptoms.

    Driving or operating machinery

    Telithromycin can cause dizziness, drowsiness, syncope, and visual impairment. Avoid driving or operating machinery or engaging in otherwise hazardous activities while taking telithromycin.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 0-2.0
    angioedema / Rapid / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    hepatic necrosis / Delayed / 0-1.0
    hepatic failure / Delayed / 0-1.0
    torsade de pointes / Rapid / 0-1.0
    pancreatitis / Delayed / 0-1.0
    erythema multiforme / Delayed / 0-0.2
    eczema vaccinatum / Delayed / 0-0.2
    bradycardia / Rapid / 0-0.2
    ventricular tachycardia / Early / Incidence not known
    myasthenia gravis / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 0-2.0
    glossitis / Early / 0-2.0
    gastritis / Delayed / 0-2.0
    stomatitis / Delayed / 0-2.0
    elevated hepatic enzymes / Delayed / 0-2.0
    blurred vision / Early / 0-2.0
    candidiasis / Delayed / 0-2.0
    vaginitis / Delayed / 0-2.0
    thrombocytosis / Delayed / 0-2.0
    palpitations / Early / 0-1.0
    confusion / Early / 0-1.0
    hallucinations / Early / 0-1.0
    hepatitis / Delayed / 0.7-0.7
    jaundice / Delayed / 0-0.7
    hyperbilirubinemia / Delayed / 0-0.2
    hypotension / Rapid / 0-0.2
    eosinophilia / Delayed / 0-0.2
    QT prolongation / Rapid / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    dyspnea / Early / Incidence not known

    Mild

    diarrhea / Early / 10.0-10.0
    nausea / Early / 7.0-7.0
    dizziness / Early / 2.8-2.8
    vomiting / Early / 2.4-2.4
    xerostomia / Early / 0-2.0
    anorexia / Delayed / 0-2.0
    flatulence / Early / 0-2.0
    abdominal pain / Early / 0-2.0
    dyspepsia / Early / 0-2.0
    rash / Early / 0-2.0
    diplopia / Early / 0-2.0
    insomnia / Early / 0-2.0
    hyperhidrosis / Delayed / 0-2.0
    drowsiness / Early / 0-2.0
    vertigo / Early / 0-2.0
    fatigue / Early / 0-2.0
    syncope / Early / 0-1.0
    myalgia / Early / 0-1.0
    muscle cramps / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    anosmia / Delayed / 0-1.0
    pruritus / Rapid / 0-0.2
    urticaria / Rapid / 0-0.2
    flushing / Rapid / 0-0.2
    anxiety / Delayed / 0-0.2
    paresthesias / Delayed / 0-0.2
    dysgeusia / Early / Incidence not known
    tremor / Early / Incidence not known
    dysosmia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Telithromycin has the potential to prolong the QT interval and should be used cautiously in combination with other drugs that may also prolong the QT interval, including abarelix.
    Abemaciclib: (Major) If coadministration with telithromycin is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If telithromycin is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of telithromycin. Abemaciclib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
    Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and telithromycin; significantly increased acalabrutinib exposure may occur. If short-term telithromycin use is unavoidable, interrupt acalabrutinib therapy. Acalabrutinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In healthy subjects, the Cmax and AUC values of acalabrutinib were increased by 3.9-fold and 5.1-fold, respectively, when acalabrutinib was coadministered with another strong inhibitor for 5 days.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with telithromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Telithromycin is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. If telithromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like telithromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If telithromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Aclidinium; Formoterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ado-Trastuzumab emtansine: (Major) Avoid coadministration of telithromycin with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until telithromycin has cleared from the circulation (approximately 3 half-lives of telithromycin) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; telithromycin is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
    Albuterol: (Minor) Use caution if short-acting beta-agonists are administered with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Alfentanil: (Moderate) Telithromycin is a competitive substrate and inhibitor of CYP3A4. Coadministration of telithromycin with other drugs metabolized by CYP3A4, including alfentanil, may result in increased plasma concentrations of alfentanil that could increase or prolong both the therapeutic and adverse effects.
    Alfuzosin: (Contraindicated) Alfuzosin is contraindicated for use with telithromycin due to the potential for serious/life-threatening reactions, including hypotension. Additive effects on the QT interval may also occur. Coadministration is expected to reduce the metabolism and increase systemic exposure to alfuzosin. Alfuzosin is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
    Aliskiren; Amlodipine: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Aliskiren; Valsartan: (Minor) Valsartan is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of valsartan with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of valsartan.
    Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with telithromycin is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and telithromycin should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
    Alosetron: (Moderate) Concomitant use of alosetron with telithromycin may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; telithromycin is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
    Alprazolam: (Contraindicated) Coadministration of telithromycin and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with telithromycin, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
    Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Telithromycin is associated with QT prolongation and torsades de pointes (TdP) and is a strong inhibitor of the CYP3A4 isoenzyme. Amiodarone is a CYP3A4 substrate. If possible, avoid coadministration of amiodarone and telithromycin. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with telithromycin. Amisulpride causes dose- and concentration- dependent QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Amlodipine: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Amlodipine; Atorvastatin: (Major) The concurrent use of telithromycin with atorvastatin is not recommended. Therapy with atorvastatin should be suspended while taking telithromycin; there are no known adverse effects with short-term discontinuation of statins. Rhabdomyolysis has been reported during concurrent use of atorvastatin and telithromycin. Telithromycin is a strong CYP3A4 inhibitor and atorvastatin is a CYP3A4 substrate. Increased exposure to atorvastatin increases the risk of myopathy and rhabdomyolysis. (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Amlodipine; Benazepril: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Amlodipine; Celecoxib: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Amlodipine; Olmesartan: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Amlodipine; Valsartan: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events. (Minor) Valsartan is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of valsartan with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of valsartan.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events. (Minor) Valsartan is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of valsartan with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of valsartan.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with telithromycin. Telithromycin is associated with QT prolongation and TdP and is a strong inhibitor of the CYP3A4 isoenzyme. Coadministration with other drugs that prolong the QT interval and are CYP3A4 substrates may result in increased concentrations of those drugs and an increased risk of adverse reactions, such as QT prolongation. Clarithromycin is a substrate for CYP3A4 and is associated with an established risk for QT prolongation and TdP. (Minor) Concentrations of omeprazole may be increased with concomitant use of telithromycin. Omeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Amprenavir: (Moderate) Concentrations of telithromycin and amprenavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Patients should be monitored for increased side effects.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include telithromycin.
    Apalutamide: (Major) Avoid coadministration of telithromycin with apalutamide due to decreased plasma concentrations of telithromycin, which may result in decreased efficacy; exposure to apalutamide may also increase. Telithromycin is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. In the presence of a strong inducer, the Cmax of telithromycin was decreased by 79% and the AUC was decreased by 86%.
    Apixaban: (Major) Reduce the apixaban dose by 50% when coadministered with drugs that are combined P-gp and strong inhibitors of CYP3A4, such as telithromycin. If patients are already receiving 2.5 mg twice daily, avoid concomitant administration. Concomitant administration results in increased exposure to apixaban and an increase in the risk of bleeding.
    Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with telithromycin since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Telithromycin is associated with QT prolongation and torsade de pointes.
    Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of telithromycin with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased telithromycin exposure may also occur. If coadministration cannot be avoided, use caution and monitor for an increase in telithromycin- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Telithromycin is a strong CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of a single oral dose of aprepitant (125 mg) on day 5 of a 10-day ketoconazole regimen (strong CYP3A4 inhibitor) increased the aprepitant AUC approximately 5-fold, and increased the mean terminal half-life by approximately 3-fold. Telithromycin is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may additionally increase plasma concentrations of telithromycin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Arformoterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Major) A dosage reduction of aripiprazole and monitoring for evidence of QT prolongation is recommended if coadministered with telithromycin. Telithromycin is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP). Aripiprazole is a CYP3A4 substrate; QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. When administered with telithromycin, the oral aripiprazole dose be reduced to one-half of the usual dose. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if telithromycin is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use telithromycin for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving telithromycin or patients receiving a combination of telithromycin and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving Abilify Maintena who are PMs and receiving telithromycin should have a dose reduction to 200 mg/month IM. Patients receiving a combination of telithromycin and a CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving telithromycin for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 mg, combined use of a strong CYP2D6 inhibitor and telithromycin for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated. Avoid concurrent use of Aristada Initio and telithromycin because the dose of Aristada Initio cannot be modified.
    Arsenic Trioxide: (Major) Arsenic trioxide administration is associated with a well-established risk of QT prolongation and torsades de pointes. Avoid the use of arsenic trioxide with other agents that may prolong the QT interval or increase the risk of torsades de pointes, including telithromycin.
    Artemether; Lumefantrine: (Major) Concurrent use of telithromycin and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if telithromycin must be used with or after artemether; lumefantrine treatment. Telithromycin is associated with QT prolongation and TdP and is a strong inhibitor of the CYP3A4 isoenzyme. Coadministration with other drugs that prolong the QT interval and are CYP3A4 substrates, such as artemether; lumefantrine, may result in increased concentrations of those drugs and an increased risk of adverse reactions, such as QT prolongation.
    Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with telithromycin is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor.
    Asenapine: (Major) Telithromycin is associated with QT prolongation and torsades de pointes (TdP) and is a strong inhibitor of the CYP3A4 isoenzyme. Coadministration with other drugs that prolong the QT interval and are CYP3A4 substrates, such as asenapine, may result in increased concentrations of those drugs and an increased risk of adverse reactions, such as QT prolongation. According to the manufacturer, asenapine should be avoided in combination with other agents also known to prolong the QT interval.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with telithromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Telithromycin is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Aspirin, ASA; Omeprazole: (Minor) Concentrations of omeprazole may be increased with concomitant use of telithromycin. Omeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. If telithromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like telithromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If telithromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Aspirin, ASA; Pravastatin: (Major) Pravastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of pravastatin with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of pravastatin.
    Atazanavir: (Major) Concentrations of telithromycin and atazanavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Patients should be monitored for increased side effects.
    Atazanavir; Cobicistat: (Major) Avoid concurrent use of telithromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentations of telithromycin, cobicistat, atazanavir and darunavir. Both telithromycin and cobicistat are strong inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of cobicistat, atazanavir and darunavir. (Major) Concentrations of telithromycin and atazanavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Patients should be monitored for increased side effects.
    Atogepant: (Major) Limit the dose of atogepant to 10 mg PO once daily if coadministered with telithromycin. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A, OATP1B1, and OATP1B3 and telithromycin is a strong CYP3A inhibitor and OATP inhibitor. Coadministration with a strong CYP3A inhibitor and OATP inhibitor resulted in a 5.5-fold and 2.85-fold increase in atogepant exposure, respectively, and a 2.15-fold and 2.23-fold increase in atogepant peak concentration, respectively.
    Atomoxetine: (Moderate) Use caution if atomoxetine is administered with telithromycin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Atorvastatin: (Major) The concurrent use of telithromycin with atorvastatin is not recommended. Therapy with atorvastatin should be suspended while taking telithromycin; there are no known adverse effects with short-term discontinuation of statins. Rhabdomyolysis has been reported during concurrent use of atorvastatin and telithromycin. Telithromycin is a strong CYP3A4 inhibitor and atorvastatin is a CYP3A4 substrate. Increased exposure to atorvastatin increases the risk of myopathy and rhabdomyolysis.
    Atorvastatin; Ezetimibe: (Major) The concurrent use of telithromycin with atorvastatin is not recommended. Therapy with atorvastatin should be suspended while taking telithromycin; there are no known adverse effects with short-term discontinuation of statins. Rhabdomyolysis has been reported during concurrent use of atorvastatin and telithromycin. Telithromycin is a strong CYP3A4 inhibitor and atorvastatin is a CYP3A4 substrate. Increased exposure to atorvastatin increases the risk of myopathy and rhabdomyolysis.
    Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of telithromycin is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold.
    Avanafil: (Major) Concomitant use of avanafil and telithromycin is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; telithromycin is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; telithromycin would be expected to have similar effects.
    Avapritinib: (Major) Avoid coadministration of avapritinib with telithromycn due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and telithromycn is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state.
    Axitinib: (Major) Avoid coadministration of axitinib with telithromycin due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after telithromycin is discontinued. Axitinib is a CYP3A4/5 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers.
    Azelastine; Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and telithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Azithromycin: (Major) Avoid coadministration of azithromycin with telithromycin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Telithromycin is also associated with QT prolongation and TdP.
    Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as telithromycin, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, telithromycin may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive prolongation of the QT interval and torsade de pointes (TdP). Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia. (Major) Concomitant administration of a CYP3A4 inducer, such as phenobarbital, with telithromycin is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with telithromycin may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of telithromycin in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Telithromycin is a strong inhibitor of CYP3A4.
    Bepridil: (Contraindicated) Bepridil administration is associated with a well-established risk of QT prolongation and torsades de pointes. Bepridil is contraindicated for use with drugs that also prolong the QT interval, including telithromycin, due to the risk of TdP.
    Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking telithromycin. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp substrate and telithromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
    Betamethasone: (Moderate) Monitor for corticosteroid-related adverse effects if coadministration is necessary. Telithromycin is a strong CYP3A4 inhibitor and betamethasone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving telithromycin. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving telithromycin. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; telithromycin inhibits P-gp.
    Bexarotene: (Major) Concomitant administration of CYP3A4 inducers, such as bexarotene, are expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy. In addition, telithromycin is a competitive substrate and inhibitor of CYP3A4; coadministration of telithromycin with other drugs metabolized by CYP3A4, such as bexarotene, may result in increased plasma concentrations and an increase of therapeutic or adverse effects.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and telithromycin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and telithromycin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Boceprevir: (Major) Close clinical monitoring is advised when administering telithromycin with boceprevir due to an increased potential for serious telithromycin-related adverse events, such as QT prolongation. If telithromycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of telithromycin and boceprevir. Telithromycin is an inhibitor of the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir is metabolized by CYP3A4 and PGP. When used in combination, the plasma concentrations of both medications may be elevated.
    Bortezomib: (Minor) Concentrations of bortezomib may be increased with concomitant use of telithromycin. Bortezomib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Bosentan: (Moderate) Bosentan may induce the metabolism of telithromycin and telithromycin may inhibit the metabolism of bosentan.
    Bosutinib: (Major) Avoid concomitant use of bosutinib and telithromycin; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. In a cross-over trial in 24 healthy volunteers, the Cmax and AUC values of bosutinib were increased 5.2-fold and 8.6-fold, respectively, when a single oral dose of bosutinib 100 mg PO was administered after 5 days of a strong CYP3A4 inhibitor.
    Brentuximab vedotin: (Minor) Concomitant administration of brentuximab vedotin and telithromycin may increase the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin. The manufacturer suggests that potent CYP3A4 inhibitors, such as telithromycin, may alter MMAE exposure as MMAE is a CYP3A4 substrate. Monitor patients for adverse reactions.
    Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as telithromycin. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Because brexpiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a moderate to strong CYP3A4 inhibitor and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level.
    Brigatinib: (Major) Avoid coadministration of brigatinib with telithromycin if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of telithromycin, resume the brigatinib dose that was tolerated prior to initiation of telithromycin. Brigatinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
    Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with telithromycin ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; telithromycin is a strong inhibitor of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Budesonide: (Minor) Concentrations of budesonide may be increased with concomitant use of telithromycin. Budesonide is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Patients should be monitored for increased side effects.
    Budesonide; Formoterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. (Minor) Concentrations of budesonide may be increased with concomitant use of telithromycin. Budesonide is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Patients should be monitored for increased side effects.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. (Minor) Concentrations of budesonide may be increased with concomitant use of telithromycin. Budesonide is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Patients should be monitored for increased side effects.
    Bupivacaine Liposomal: (Moderate) Telithromycin is an inhibitor of and bupivacaine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased concentrations of bupivicaine.
    Bupivacaine: (Moderate) Telithromycin is an inhibitor of and bupivacaine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased concentrations of bupivicaine.
    Bupivacaine; Epinephrine: (Moderate) Telithromycin is an inhibitor of and bupivacaine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased concentrations of bupivicaine.
    Bupivacaine; Lidocaine: (Moderate) Telithromycin is an inhibitor of and bupivacaine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased concentrations of bupivicaine. (Moderate) Telithromycin, a ketolide antibiotic, can compete with lidocaine for metabolism by CYP3A4. This can result in increased systemic concentrations of lidocaine if the two drugs are coadministered.
    Bupivacaine; Meloxicam: (Moderate) Telithromycin is an inhibitor of and bupivacaine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased concentrations of bupivicaine.
    Buprenorphine: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of telithromycin and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Telithromycin also has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a strong CYP3A4 inhibitor such as telithromycin may decrease the clearance of buprenorphine further increasing the risk of QT prolongation and prolonged or increased opioid effects. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of telithromycin and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Telithromycin also has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a strong CYP3A4 inhibitor such as telithromycin may decrease the clearance of buprenorphine further increasing the risk of QT prolongation and prolonged or increased opioid effects. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Buspirone: (Moderate) Concentrations of buspirone may be increased with concomitant use of telithromycin. Buspirone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with telithromycin if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and telithromycin is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
    Cabotegravir; Rilpivirine: (Major) When possible, alternative antibiotics to telithromycin should be considered in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation and rilpivirine-related adverse effects. Rilpivirine is a CYP3A4 substrate that has caused QT prolongation in supratherapeutic doses (75 to 300 mg/day). Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
    Cabozantinib: (Major) Avoid concomitant use of cabozantinib and telithromycin due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with telithromycin 2 to 3 days after discontinuation of telithromycin. Cabozantinib is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
    Calcifediol: (Moderate) Dose adjustment of calcifediol may be necessary during coadministration with telithromycin. Additionally, serum 25-hydroxyvitamin D, intact PTH, and calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with telithromycin. Telithromycin, which is a cytochrome P450 inhibitor, may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1) and may alter serum concentrations of calcifediol.
    Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with telithromycin is necessary. Capmatinib is a CYP3A substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%.
    Carbamazepine: (Moderate) Telithromycin is a competitive substrate and inhibitor of CYP3A4. Coadministration of telithromycin with other drugs metabolized by CYP3A4, including carbamazepine, may result in increased plasma concentrations of carbamazepine. Carbamazepine may also induce the metabolism of telithromycin, causing a loss of efficacy.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as telithromycin, is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For adult patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased. When initiating cariprazine in a patient who is stable on a strong CYP3A4 inhibitor, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased.
    Ceritinib: (Major) Avoid concomitant use of ceritinib with telithromycin due to increased exposure to both drugs which may increase the incidence and severity of adverse reactions; QT prolongation may also occur. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. Also, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. After telithromycin is discontinued, resume the dose of ceritinib taken prior to initiating telithromycin. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. In the presence of strong inhibitors, telithromycin exposure increased up to 95%. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Concentration-dependent QT prolongation has been reported with ceritinib therapy.
    Chloramphenicol: (Moderate) Concentrations of telithromycin may be increased with concomitant use of chloramphenicol. Telithromycin is a substrate of CYP3A4 and chloramphenicol is a potent CYP3A4 inhibitor.
    Chlordiazepoxide: (Moderate) Chlordiazepoxide is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Chlordiazepoxide; Amitriptyline: (Moderate) Chlordiazepoxide is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Chlordiazepoxide; Clidinium: (Moderate) Chlordiazepoxide is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Chloroquine: (Major) Avoid coadministration of chloroquine with telithromycin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Telithromycin is also associated with QT prolongation and TdP.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with telithromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Telithromycin is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with telithromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Telithromycin is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpromazine: (Major) Concurrent use of chlorpromazine and telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Telithromycin is associated QT prolongation and TdP. Chlorpromazine is also associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Cilostazol: (Major) Concentrations of cilostazol may be increased with concomitant use of telithromycin. Cilostazol is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Cinacalcet: (Major) Concentrations of cinacalcet may be increased with concomitant use of telithromycin. Cinacalcet is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Ciprofloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with ciprofloxacin. Telithromycin is associated with QT prolongation and TdP. Ciprofloxacin has been associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of cisapride with telithromycin is contraindicated. Postmarketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including TDP and death, when known and potent inhibitors of CYP3A4, such as telithromycin, are coadministered with cisapride.
    Citalopram: (Major) Concurrent use of telithromycin and citalopram should be avoided if possible. Telithromycin has the potential to prolong the QT interval. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval. In addition, citalopram concentrations may be increased with concomitant use. Citalopram is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with telithromycin. Telithromycin is associated with QT prolongation and TdP and is a strong inhibitor of the CYP3A4 isoenzyme. Coadministration with other drugs that prolong the QT interval and are CYP3A4 substrates may result in increased concentrations of those drugs and an increased risk of adverse reactions, such as QT prolongation. Clarithromycin is a substrate for CYP3A4 and is associated with an established risk for QT prolongation and TdP.
    Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of telithromycin as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; telithromycin is a strong inhibitor of CYP3A4.
    Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and telithromycin, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with telithromycin. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Telithromycin is associated with QT prolongation and TdP.
    Clonazepam: (Moderate) Use telithromycin cautiously and carefully monitor patients receiving concurrent clonazepam due to impaired metabolism of clonazepam leading to exaggerated concentrations and adverse effects, such as CNS and/or respiratory depression. Clonazepam is a CYP3A4 substrate. Telithromycin is a CYP3A4 inhibitor.
    Clorazepate: (Moderate) Clorazepate is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with telithromycin and monitor for adverse reactions, including QT prolongation. If telithromycin is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine and additive effects on the QT interval may occur during concurrent use. Clozapine is partially metabolized by CYP3A4 and has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and TdP.
    Cobicistat: (Major) Avoid concurrent use of telithromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentations of telithromycin, cobicistat, atazanavir and darunavir. Both telithromycin and cobicistat are strong inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of cobicistat, atazanavir and darunavir.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with telithromycin due to the risk of cobimetinib toxicity. Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; telithromycin is a weak P-gp inhibitor as well as a strong CYP3A inhibitor. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), another strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
    Codeine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4. (Moderate) Use caution as coadministration of telithromycin and promethazine may increase the risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with telithromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Telithromycin is a strong inhibitor of CYP3A4. (Moderate) Use caution as coadministration of telithromycin and promethazine may increase the risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and telithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Telithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken telithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Conivaptan: (Contraindicated) Coadministration of conivaptan and telithromycin is contraindicated due to the potential for increased conivaptan exposure. Conivaptan is a CYP3A substrate; telithromycin is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with telithromycin, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
    Copanlisib: (Major) Avoid the concomitant use of copanlisib and telithromycin if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; telithromycin is a strong CYP3A inhibitor.
    Crizotinib: (Major) Avoid concomitant use of telithromycin and crizotinib due to increased plasma concentrations of crizotinib, which may increase the incidence and severity of adverse reactions; additive QT prolongation may also occur. If concomitant use is necessary for patients with non-small cell lung cancer, reduce the dose of crizotinib to 250 mg PO once daily. If concomitant use is necessary for patients with anaplastic large cell lymphoma, reduce the dose of crizotinib to 250 mg PO twice daily for BSA of 1.7 m2 or more; 200 mg PO twice daily for BSA of 1.17 to 1.69 m2; and 250 mg PO once daily for BSA of 0.81 to 1.16 m2; do not use this combination in patients with a BSA of 0.6 to 0.8 m2. Monitor ECGs for QT prolongation and monitor electrolytes. Resume the original crizotinib dose after discontinuation of telithromycin. Crizotinib is a CYP3A substrate that has been associated with concentration-dependent QT prolongation. Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with one strong CYP3A inhibitor increased the AUC of single-dose crizotinib by 216%. Concomitant use with another strong CYP3A4 inhibitor increased the steady-state AUC of crizotinib by 57% compared to crizotinib alone.
    Cyclosporine: (Moderate) Telithromycin is a competitive substrate and inhibitor of CYP3A4. Coadministration of telithromycin with other drugs metabolized by CYP3A4, including cyclosporine, may result in increased plasma concentrations of cyclosporine that could increase or prolong both the therapeutic and adverse effects.
    Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with telithromycin, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like telithromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with telithromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
    Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as telithromycin. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
    Danazol: (Moderate) Concentrations of telithromycin may be increased with concomitant use of danazol. Telithromycin is a substrate of CYP3A4 and danazol is a CYP3A4 inhibitor.
    Dapagliflozin; Saxagliptin: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP 3A4/5 inhibitor such as telithromycin.
    Dapsone: (Minor) Concentrations of dapsone may be increased with concomitant use of telithromycin. Dapsone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with telithromycin due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor.
    Darolutamide: (Moderate) Monitor patients more frequently for darolutamide-related adverse reactions if coadministration with telithromycin is necessary due to the risk of increased darolutamide exposure; decrease the dose of darolutamide for grade 3 or 4 adverse reactions or for otherwise intolerable adverse reactions. Telithromycin is a P-glycoprotein (P-gp) inhibitor and a strong CYP3A4 inhibitor; darolutamide is a CYP3A4 substrate. Concomitant use with another combined P-gp inhibitor and strong CYP3A4 inhibitor increased the mean AUC and Cmax of darolutamide by 1.7-fold and 1.4-fold, respectively.
    Darunavir: (Moderate) Concentrations of telithromycin and darunavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Additionally, darunavir is administered ('boosted') with ritonavir, which is a potent CYP3A4 inhibitior. Patients should be monitored for increased side effects.
    Darunavir; Cobicistat: (Major) Avoid concurrent use of telithromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentations of telithromycin, cobicistat, atazanavir and darunavir. Both telithromycin and cobicistat are strong inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of cobicistat, atazanavir and darunavir. (Moderate) Concentrations of telithromycin and darunavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Additionally, darunavir is administered ('boosted') with ritonavir, which is a potent CYP3A4 inhibitior. Patients should be monitored for increased side effects.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concurrent use of telithromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentations of telithromycin, cobicistat, atazanavir and darunavir. Both telithromycin and cobicistat are strong inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of cobicistat, atazanavir and darunavir. (Moderate) Concentrations of telithromycin and darunavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Additionally, darunavir is administered ('boosted') with ritonavir, which is a potent CYP3A4 inhibitior. Patients should be monitored for increased side effects.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of telithromycin and ritonavir due to increased telithromycin exposure which may increase the risk of QT prolongation; ritonavir exposure may also increase. Both drugs are substrates and strong inhibitors of CYP3A4. (Major) Concurrent administration of telithromycin with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of all 5 drugs and subsequent adverse effects. There may be a risk of QT prolongation when these drugs are administered together. While dasabuvir; ombitasvir; paritaprevir; ritonavir did not prolong the QT interval to a clinically relevant extent in healthy subjects, ritonavir has been associated with dose-related QT prolongation in other trials. Telithromycin also has the potential to cause QT prolongation. Both ritonavir and telithromycin are substrates and potent inhibitors of the hepatic isoenzyme CYP3A4; paritaprevir and dasabuvir (minor) are CYP3A4 substrates. In addition, telithromycin inhibits the drug transporter P-glycoprotein (P-gp); dasabuvir, ombitasvir, paritaprevir and ritonavir are all substrates of P-gp. Telithromycin also inhibits the organic anion transporting polypeptides (OATP). Paritaprevir is a substrate of OATP1B1 and OATP1B3. Caution and close monitoring is advised if these drugs are administered together. (Major) Concurrent administration of telithromycin with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of both drugs and subsequent adverse effects. There may be a risk of QT prolongation when these drugs are administered together. While dasabuvir; ombitasvir; paritaprevir; ritonavir and ombitasvir; paritaprevir; ritonavir did not prolong the QT interval to a clinically relevant extent in healthy subjects, ritonavir has been associated with dose-related QT prolongation in other trials. Telithromycin also has the potential to cause QT prolongation. Both ritonavir and telithromycin are substrates and potent inhibitors of the hepatic isoenzyme CYP3A4; paritaprevir and dasabuvir (minor) are CYP3A4 substrates. In addition, telithromycin inhibits the drug transporter P-glycoprotein (P-gp); dasabuvir, ombitasvir, paritaprevir and ritonavir are all substrates of P-gp. Telithromycin also inhibits the organic anion transporting polypeptides (OATP). Paritaprevir is a substrate of OATP1B1 and OATP1B3. Caution and close monitoring is advised if these drugs are administered together.
    Dasatinib: (Major) Avoid coadministration of dasatinib and telithromycin due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to telithromycin with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of telithromycin in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue telithromycin or stop dasatinib until telithromycin is discontinued. Allow a washout of approximately 1 week after telithromycin is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and TdP. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with telithromycin. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; telithromycin is a strong inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
    Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Telithromycin is associated with QT prolongation and torsades de pointes (TdP).
    Delavirdine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as telithromycin, should be expected with concurrent use of delavirdine.
    Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and telithromycin. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Dexamethasone: (Major) Concentrations of dexamethasone may be increased and concentrations of telithromycin may be decreased with coadministration. Dexamethasone is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Additionally, dexamethasone is a CYP3A4 inducer, while telithromycin is CYP3A4 substrate.
    Dexlansoprazole: (Minor) Concentrations of dexlansoprazole may be increased with concomitant use of telithromycin. Dexlansoprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Dextromethorphan; Quinidine: (Major) Concurrent use of quinidine and/or quinidine-containing products (e.g., dextromethorphan; quinidinne) with telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The manufacturer of dextromethorphan; quinidine recommends an initial ECG evaluation (baseline and 3 to 4 hours post-dose) in patients taking dextromethorphan; quinidine in combination with moderate or strong CYP3A4 inhibitors such as telithromycin. The quinidine component of dextromethorphan; quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of dextromethorphan; quinidine with moderate or strong CYP3A4 inhibitors may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects. In addition, telithromycin has the potential to prolong the QTc interval in some patients.
    Diazepam: (Moderate) Diazepam is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Diclofenac: (Minor) Concentrations of diclofenac may be increased with concomitant use of telithromycin. Diclofenac is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Diclofenac; Misoprostol: (Minor) Concentrations of diclofenac may be increased with concomitant use of telithromycin. Diclofenac is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Digoxin: (Moderate) Concomitant administration of telithromycin and digoxin increased digoxin peak and trough plasma levels by 73% and 21%, respectively, in healthy volunteers. However, trough levels ranged from 0.74 to 2.17 ng/ml. There were no significant ECG changes and no signs of digoxin toxicity. Monitoring of digoxin adverse effects or serum levels should be considered during administration with telithromycin.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with telithromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of telithromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If telithromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Telithromycin is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Dihydroergotamine: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Diltiazem: (Moderate) Telithromycin, a ketolide antibiotic, can compete with diltiazem for metabolism by CYP3A4. This can result in increased concentrations of diltiazem if the two drugs are coadministered.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Disopyramide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with disopyramide. Both disopyramide and telithromycin are associated with QT prolongation and TdP. Additionally, disopyramide is a substrate for CYP3A4 and telithromycin is a strong inhibitor of this enzyme. Coadministration may result in increased disopyramide concentrations and an increased risk of adverse reactions, such as QT prolongation.
    Disulfiram: (Minor) Concentrations of disulfiram may be increased with concomitant use of telithromycin. Disulfiram is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Docetaxel: (Major) Avoid coadministration of docetaxel with telithromycin if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Dofetilide: (Major) Coadministration of dofetilide and telithromycin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Telithromycin is also associated with QT prolongation and TdP.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Major) When possible, alternative antibiotics to telithromycin should be considered in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation and rilpivirine-related adverse effects. Rilpivirine is a CYP3A4 substrate that has caused QT prolongation in supratherapeutic doses (75 to 300 mg/day). Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
    Donepezil: (Moderate) Use donepezil with caution in combination with telithromycin as concurrent use may increase the risk of QT prolongation. Clinical monitoring for donepezil-related adverse effects, such as GI or cholinergic effects, is also recommended. The plasma concentrations of donepezil may be elevated when administered concurrently with telithromycin. Both donepezil and telithromycin are associated with QT prolongation and torsade de pointes (TdP). In addition, telithromycin is a strong CYP3A4 inhibitor; donepezil is partially metabolized by CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased mean donepezil concentrations by 36%. The clinical significance of this increase is unknown.
    Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with telithromycin as concurrent use may increase the risk of QT prolongation. Clinical monitoring for donepezil-related adverse effects, such as GI or cholinergic effects, is also recommended. The plasma concentrations of donepezil may be elevated when administered concurrently with telithromycin. Both donepezil and telithromycin are associated with QT prolongation and torsade de pointes (TdP). In addition, telithromycin is a strong CYP3A4 inhibitor; donepezil is partially metabolized by CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased mean donepezil concentrations by 36%. The clinical significance of this increase is unknown.
    Doravirine: (Minor) Coadministration of doravirine and telithromycin may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; telithromycin is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Minor) Coadministration of doravirine and telithromycin may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; telithromycin is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
    Doxazosin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with telithromycin. Telithromycin is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Doxorubicin Liposomal: (Major) Avoid coadministration of telithromycin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Telithromycin is a strong CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYP3A4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
    Doxorubicin: (Major) Avoid coadministration of telithromycin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Telithromycin is a strong CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYP3A4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
    Dronabinol: (Major) Use caution if coadministration of dronabinol with telithromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; telithromycin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Concomitant administration of telithromycin with another CYP3A4 substrate, midazolam, resulted in 2-fold (IV) and 6-fold (PO) increases in the AUC of midazolam.
    Dronedarone: (Contraindicated) Concomitant use of dronedarone with telithromycin is contraindicated. Dronedarone is metabolized by CYP3A, and telithromycin is a strong inhibitor of CYP3A4. Repeated doses of ketoconazole, also a strong CYP3A4 inhibitor, increased dronedarone exposure 17-fold and increased dronedarone Cmax 9-fold. In addition, telithromycin has been established to have a possible risk of QT prolongation and Torsade de Pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval, such as telithromycin, should not be coadministered with droperidol. Telithromycin is also a strong inhibitor of the CYP3A4 isoenzyme. Coadministration with CYP3A4 substrates, such as droperidol, may result in increased concentrations of those drugs and an increased risk of adverse reactions, such as QT prolongation.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Dutasteride: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like telithromycin are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Dutasteride; Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of telithromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as telithromycin, should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like telithromycin are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with telithromycin. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; telithromycin is a substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as telithromycin.
    Edoxaban: (Moderate) Coadministration of edoxaban and telithromycin may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and telithromycin is a mild P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of telithromycin; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with telithromycin as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Telithromycin is associated with QT prolongation and TdP. In addiiton, concentrations of efavirenz may be increased and the concentrations of telithromycin may be decreased with coadministration. Efavirenz is a CYP3A4 substrate and inducer, while telithromycin is a CYP3A4 substrate and a strong CYP3A4 inhibitor.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Consider alternatives to efavirenz when coadministering with telithromycin as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Telithromycin is associated with QT prolongation and TdP. In addiiton, concentrations of efavirenz may be increased and the concentrations of telithromycin may be decreased with coadministration. Efavirenz is a CYP3A4 substrate and inducer, while telithromycin is a CYP3A4 substrate and a strong CYP3A4 inhibitor.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Consider alternatives to efavirenz when coadministering with telithromycin as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Telithromycin is associated with QT prolongation and TdP. In addiiton, concentrations of efavirenz may be increased and the concentrations of telithromycin may be decreased with coadministration. Efavirenz is a CYP3A4 substrate and inducer, while telithromycin is a CYP3A4 substrate and a strong CYP3A4 inhibitor.
    Elagolix: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as telithromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Telithromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to telithromycin in a patient receiving elagolix.
    Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as telithromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Telithromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to telithromycin in a patient receiving elagolix. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Elbasvir; Grazoprevir: (Contraindicated) Concurrent administration of elbasvir; grazoprevir with telithromycin is contraindicated. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir and grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations). Telithromycin is a strong inhibitor of the hepatic enzyme CYP3A and the organic anion transporting polypeptide (OATP1B1/3). Elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a substrate of OATP1B1/3.
    Eletriptan: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of telithromycin due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; telithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Elexacaftor; tezacaftor; ivacaftor: (Major) If telithromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor when coadministered with telithromycin; coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 2 elexacaftor/tezacaftor/ivacaftor combination tablets twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive substrate); telithromycin is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with telithromycin; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); telithromycin is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
    Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of telithromycin and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both telithromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and telithromycin can independently prolong the QT interval, and coadministration increases this risk. Telithromycin is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
    Eluxadoline: (Major) When administered concurrently with telithromycin, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); telithromycin is an in vitro inhibitor of OATP1B1/1B3. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concurrent use of telithromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentations of telithromycin, cobicistat, atazanavir and darunavir. Both telithromycin and cobicistat are strong inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of cobicistat, atazanavir and darunavir.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of telithromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentations of telithromycin, cobicistat, atazanavir and darunavir. Both telithromycin and cobicistat are strong inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of cobicistat, atazanavir and darunavir. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) When possible, alternative antibiotics to telithromycin should be considered in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation and rilpivirine-related adverse effects. Rilpivirine is a CYP3A4 substrate that has caused QT prolongation in supratherapeutic doses (75 to 300 mg/day). Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) When possible, alternative antibiotics to telithromycin should be considered in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation and rilpivirine-related adverse effects. Rilpivirine is a CYP3A4 substrate that has caused QT prolongation in supratherapeutic doses (75 to 300 mg/day). Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enalapril; Felodipine: (Moderate) Telithromycin, a ketolide antibiotic, can theoretically compete with felodipine for metabolism by CYP3A4. This can result in increased concentrations of felodipine if the two drugs are coadministered.
    Encorafenib: (Major) Avoid coadministration of encorafenib and telithromycin due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of telithromycin. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. If telithromycin is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of telithromycin. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
    Enfortumab vedotin: (Moderate) Closely monitor for signs of enfortumab vedotin-related adverse reactions if concurrent use with telithromycin is necessary. Concomitant use may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the incidence or severity of enfortumab-vedotin toxicities. MMAE, the microtubule-disrupting component of enfortumab vedotin, is a CYP3A4 and P-gp substrate; telithromycin is a dual P-gp/strong CYP3A4 inhibitor. Based on physiologically-based pharmacokinetic (PBPK) modeling predictions, concomitant use of enfortumab vedotin with another dual P-gp/strong CYP3A4 inhibitor is predicted to increase the exposure of unconjugated MMAE by 38%.
    Entrectinib: (Major) Avoid coadministration of entrectinib with telithromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If telithromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of telithromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
    Enzalutamide: (Major) Avoid coadministration of telithromycin with enzalutamide due to decreased plasma concentrations of telithromycin, which may result in decreased efficacy. Telithromycin is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. In the presence of a strong inducer, the Cmax of telithromycin was decreased by 79% and the AUC was decreased by 86%.
    Eplerenone: (Contraindicated) Coadministration of telithromycin and eplerenone is contraindicated. Telithromycin potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
    Erdafitinib: (Major) Avoid coadministration of erdafitinib and telithromycin due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If telithromycin is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Ergoloid Mesylates: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Ergonovine: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Ergot alkaloids: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Ergotamine: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Ergotamine; Caffeine: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as telithromycin, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erlotinib: (Major) Avoid coadministration of erlotinib with telithromycin if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
    Escitalopram: (Moderate) Use escitalopram with caution in combination with telithromycin as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Telithromycin is associated with QT prolongation and TdP.
    Esomeprazole: (Minor) Concentrations of esomeprazole may be increased with concomitant use of telithromycin. Esomeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Estazolam: (Moderate) Telithromycin is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with telithromycin, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Estradiol; Progesterone: (Moderate) Use caution if coadministration of telithromycin with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Telithromycin is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
    Eszopiclone: (Major) The adult dose of eszopiclone should not exceed 2 mg/day during co-administration of potent CYP3A4 inhibitors, such as telithromycin. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day psychomotor or memory impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Ethosuximide: (Moderate) Concentrations of ethosuximide may be increased with concomitant use of telithromycin. Ethosuximide is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Etonogestrel: (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as telithromycin may increase the serum concentration of etonogestrel.
    Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin. (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as telithromycin may increase the serum concentration of etonogestrel.
    Etravirine: (Major) Concomitant administration of CYP3A4 inducers, such as etravirine, are expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy. In addition, telithromycin is a competitive substrate and inhibitor of CYP3A4; coadministration of telithromycin with other drugs metabolized by CYP3A4, such as etravirine, may result in increased plasma concentrations and an increase of therapeutic or adverse effects.
    Everolimus: (Major) Avoid coadministration of everolimus with telithromycin due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Telithromycin is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold.
    Ezetimibe; Simvastatin: (Contraindicated) Telithromycin is contraindicated during simvastatin therapy. Telithromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, therapy with simvastatin must be suspended during telithromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin. Pharmacokinetic studies have reported increased simvastatin concentrations due to CYP3A4 inhibition by telithromycin. When the two drugs were coadministered, there was a 5.3-fold increase in simvastatin Cmax, an 8.9-fold increase in the AUC, a 15-fold increase in the active metabolite Cmax, and a 12-fold increase in the active metabolite AUC. In another study, when simvastatin and telithromycin were administered 12 hours apart, there was a 3.4-fold increase in simvastatin Cmax, a 4-fold increase in AUC, a 3.2-fold increase in the active metabolite Cmax, and a 4.3-fold increase in the active metabolite AUC. Increased serum concentrations of HMG-CoA reductase inhibitors are associated with myopathy. Additionally, simvastatin is a substrate for organic anion transport protein (OATP) and telithromycin may act as an inhibitor for the hepatic organic anion transport protein (OATP) uptake transporters OATP1B1 and OATP1B3.
    Ezogabine: (Moderate) Use caution during concurrent use of ezogabine and telithromycin as concurrent use may increase the risk of QT prolongation. Ezogabine has been associated with QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Fedratinib: (Major) Avoid coadministration of fedratinib with telithromycin as concurrent use may increase fedratinib exposure; telithromycin exposure may also increase. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If telithromycin is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate and moderate CYP3A4 inhibitor; telithromycin is a strong CYP3A4 inhibitor and CYP 3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
    Felodipine: (Moderate) Telithromycin, a ketolide antibiotic, can theoretically compete with felodipine for metabolism by CYP3A4. This can result in increased concentrations of felodipine if the two drugs are coadministered.
    Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. If telithromycin is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If telithromycin is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
    Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with telithromycin. Avoid use of fesoterodine and telithromycin in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
    Finerenone: (Contraindicated) Concomitant use of finerenone and telithromycin is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
    Fingolimod: (Moderate) Caution is advised as coadministration of telithromycin and fingolimod may increase the risk for QT prolongation and torsade de pointes (TdP). Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with flecainide. Telithromycin is associated with QT prolongation and TdP. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
    Flibanserin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as telithromycin, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
    Fluconazole: (Contraindicated) Concurrent use of fluconazole and telithromycin is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of telithromycin. These drugs used in combination may result in elevated telithromycin plasma concentrations, causing an increased risk for telithromycin-related adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as telithromycin.
    Fluoxetine: (Moderate) Use fluoxetine with caution in combination with telithromycin. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Telithromycin is also associated with QT prolongation and TdP.
    Fluphenazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with fluphenazine. Telithromycin is associated with QT prolongation and TdP. Fluphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    Flurazepam: (Moderate) Flurazepam is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and telithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Fluticasone; Salmeterol: (Major) Coadministration of inhaled fluticasone propionate and telithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and telithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and telithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluvastatin: (Major) Fluvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Coadministration of fluvastatin with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of fluvastatin.
    Fluvoxamine: (Moderate) Use caution as coadministration of telithromycin and fluvoxamine may increase the risk for QT prolongation, torsade de pointes (TdP), and elevated telithromycin concentrations. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Telithromycin is associated with QT prolongation and TdP. In addition, concentrations of telithromycin may be increased with concomitant use of fluvoxamine because telithromycin is a substrate of CYP3A4 and fluvoxamine is a moderate CYP3A4 inhibitor.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with telithromycin. Telithromycin is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with telithromycin, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Formoterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Concomitant administration of telithromycin and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with telithromycin long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fosamprenavir: (Moderate) Concentrations of fosamprenavir may be increased and the concentrations of telithromycin may be altered with coadministration. Fosamprenavir is a CYP3A4 substrate, inhibitor, and may be and inducer, while telithromycin is a CYP3A4 substrate and a strong CYP3A4 inhibitor. In addition, fosamprenavir is a substrate for the drug transporter P-glycoprotein (P-gp); telithromycin is a P-gp inhibitor.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as telithromycin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Telithromycin is also associated with QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: (Major) Concomitant administration of CYP3A4 inducers like fosphenytoin is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; telithromycin is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
    Fostemsavir: (Moderate) Use telithromycin and fostemsavir together with caution due to the potential for QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with telithromycin is necessary. Gefitinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
    Gemifloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with gemifloxacin. Telithromycin is associated with QT prolongation and TdP. Gemifloxacin may prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and telithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Telithromycin is also associated with QT prolongation and TdP.
    Gilteritinib: (Major) Consider an alternative to telithromycin during treatment with gilteritinib due to increased gilteritinib exposure and the potential for additive QT prolongation. If coadministration is required, frequently monitor for gilteritinib-related adverse effects and cardiac toxicity. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study. Both drugs have been associated with QT prolongation.
    Glasdegib: (Major) Consider an alternative to telithromycin during treatment with glasdegib due to the potential for additive QT prolongation and increased glasdegib exposure. If coadministration cannot be avoided, monitor for increased glasdegib-related adverse events and for increased risk of QT prolongation with more frequent ECG monitoring. Glasdegib is a CYP3A4 substrate that may cause QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and telithromycin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and P-glycoprotein (P-gp); telithromycin is an inhibitor of these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and telithromycin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); telithromycin is an inhibitor of P-gp.
    Glimepiride; Rosiglitazone: (Moderate) Monitor for an increase in rosiglitazone-related adverse effects during concomitant use with telithromycin; adjust the dose of rosiglitazone based on clinical response. Coadministration may increase the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and telithromycin is a weak CYP2C8 inhibitor.
    Glycopyrrolate; Formoterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval.
    Granisetron: (Moderate) Use granisetron with caution in combination with telithromycin due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Guanfacine: (Major) Telithromycin may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If telithromycin is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and telithromycin is a strong CYP3A4 inhibitor.
    Halofantrine: (Major) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes and should be avoided in combination with other drugs that prolong the QT interval, including telithromycin.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with telithromycin. Halogenated anesthetics can prolong the QT interval. Telithromycin is associated with QT prolongation and torsades de pointes (TdP).
    Haloperidol: (Moderate) Use telithromycin with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. A haloperidol dose reduction may be necessary. Telithromycin is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP). Haloperidol is a CYP3A4 substrate; QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
    Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like telithromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If telithromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydroxychloroquine: (Major) Avoid coadministration of telithromycin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with telithromycin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Telithromycin is also associated with QT prolongation and TdP.
    Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with telithromycin. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
    Ibrutinib: (Major) Avoid the concomitant use of ibrutinib and telithromycin; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). If short-term use of telithromycin is necessary (e.g., 7 days or less), interrupt ibrutinib treatment. Resume ibrutinib at the previous dose when telithromycin is discontinued. Ibrutinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of other strong CYP3A4 inhibitors, the Cmax and AUC values of ibrutinib were increased significantly.
    Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. If telithromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like telithromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If telithromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Ibutilide: (Major) Telithromycin is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP, such as ibutilide, should be used cautiously with telithromycin. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
    Idelalisib: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and telithromycin, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while telithromycin is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and telithromycin.
    Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with telithromycin is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Telithromycin is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
    Iloperidone: (Major) Avoid coadministration of iloperidone and telithromycin due to the potential for QT prolongation. If coadministration cannot be avoided, reduce the iloperidone dose by one-half. If telithromycin is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may also occur with concurrent use. Iloperidone is a CYP3A4 substrate that has been associated with QT prolongation. Telithromycin is a strong CYP3A4 inhibitor that has also been associated with QT prolongation and torsade de pointes. Coadministration of another strong CYP3A4 inhibitor increased the AUC of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively.
    Imatinib: (Moderate) Concentrations of telithromycin and imatinib, STI-571 may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Additionally, imatninib is a substrate for P-glycoprotein (PGP) and telithromycin is a potential PGP inhibitor. Patients should be monitored for increased side effects.
    Indacaterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indinavir: (Minor) Telithromycin is a competitive substrate and inhibitor of CYP3A4. Coadministration of telithromycin with other drugs metabolized by CYP3A4, such as indinavir, may result in increased plasma concentrations of the other drugs and could increase or prolong both the therapeutic and adverse effects.
    Infigratinib: (Major) Avoid concomitant use of infigratinib and telithromycin. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with telithromycin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Telithromycin is also associated with QT prolongation and TdP.
    Ipratropium; Albuterol: (Minor) Use caution if short-acting beta-agonists are administered with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Irinotecan Liposomal: (Major) Avoid administration of telithromycin during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 and UGT1A1 inhibitor increased exposure to both irinotecan and its active metabolite, SN-38; concomitant use of other strong CYP3A4 inhibitors may also increase systemic exposure.
    Irinotecan: (Major) Avoid administration of telithromycin during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 and UGT1A1 inhibitor increased exposure to both irinotecan and its active metabolite, SN-38; concomitant use of other strong CYP3A4 inhibitors may also increase systemic exposure.
    Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with telithromycin is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; telithromycin is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated telithromycin concentrations would also be expected with coadministration, as telithromycin is a CYP3A4 substrate and isavuconazole is a moderate CYP3A4 inhibitor.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Concomitant use of telithromycin and rifampin, a potent CYP3A4 inducer, should be avoided. During administration in repeated doses, the Cmax and AUC of telithromycin were decreased by 79% and 86%, respectively. This is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Isoniazid, INH; Rifampin: (Contraindicated) Concomitant use of telithromycin and rifampin, a potent CYP3A4 inducer, should be avoided. During administration in repeated doses, the Cmax and AUC of telithromycin were decreased by 79% and 86%, respectively. This is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Isradipine: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as isradipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with telithromycin as istradefylline exposure and adverse effects may increase. Telithromycin is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
    Itraconazole: (Major) Coadministration of telithromycin and itraconazole is contraindicated in patients with severe renal or hepatic dysfunction. In patients with normal renal and hepatic function, avoid coadministration. If concurrent use cannot be avoided, use caution and close monitoring is advised. The potent CYP3A4 inhibitory effect of itraconazole has been found to increase the Cmax and AUC of telithromycin (a CYP3A4 substrate) by 22% and 54%, respectively. This interaction may be exaggerated in patients with renal or hepatic dysfunction. In addition, both telithromycin and itraconazole have been associated with QT prolongation; coadministration may increase this risk. If itraconazole therapy is stopped, it may be prudent to continue close monitoring for up to 2 weeks after discontinuing itraconazole. Once discontinued, the plasma concentration of itraconazole decreases to almost undetectable concentrations within 7 to 14 days. The decline in plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
    Ivabradine: (Contraindicated) Coadministration of ivabradine and telithromycin is contraindicated. Ivabradine is primarily metabolized by CYP3A4; telithromycin is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
    Ivacaftor: (Major) If telithromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with telithromycin due to increased plasma concentrations of ivosidenib and additive QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If telithromycin is discontinued, wait at least 5 half-lives of telithromycin before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Telithromycin is a strong CYP3A4 associated with QT prolongation and torsade de pointes (TdP). Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
    Ixabepilone: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as telithromycin should be avoided. In addition, ixabepilone is a P-glycoprotein (Pgp) substrate and telithromycin is a Pgp inhibitor. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Ketoconazole: (Major) Avoid concurrent administration of ketoconazole and telithromycin. Coadministration results in elevated plasma concentrations of telithromycin and an increased risk for adverse events. A multi-dose interaction study found coadministration resulted in an increase of the Cmax and AUC of telithromycin by 51% and 95%, respectively. In addition, use of these drugs together may increase the risk for QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP); ketoconazole can also prolong the QT interval.
    Lacosamide: (Moderate) Use caution during concurrent use of lacosamide and telithromycin, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; telithromycin is a strong inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadministered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as telithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Lansoprazole: (Minor) Concentrations of lansoprazole may be increased with concomitant use of telithromycin. Lansoprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with telithromycin. Telithromycin is associated with QT prolongation and TdP and is a strong inhibitor of the CYP3A4 isoenzyme. Coadministration with other drugs that prolong the QT interval and are CYP3A4 substrates may result in increased concentrations of those drugs and an increased risk of adverse reactions, such as QT prolongation. Clarithromycin is a substrate for CYP3A4 and is associated with an established risk for QT prolongation and TdP. (Minor) Concentrations of lansoprazole may be increased with concomitant use of telithromycin. Lansoprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Lansoprazole; Naproxen: (Minor) Concentrations of lansoprazole may be increased with concomitant use of telithromycin. Lansoprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Lapatinib: (Major) Avoid coadministration of lapatinib with telithromycin due to increased plasma concentrations of lapatinib; QT prolongation may also occur. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. If telithromycin is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Telithromycin is a strong CYP3A4 inhibitor that is also associated with QT prolongation and torsade de pointes (TdP). Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold.
    Larotrectinib: (Major) Avoid coadministration of larotrectinib with telithromycin due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If telithromycin is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of telithromycin. Larotrectinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study.
    Lefamulin: (Major) Avoid coadministration of lefamulin with telithromycin as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Telithromycin is a P-gp and strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes. Coadministration of a combined P-gp and strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
    Lemborexant: (Major) Avoid coadministration of lemborexant and telithromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with telithromycin due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Telithromycin is also associated with QT prolongation and torsade de pointes (TdP).
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of telithromycin; monitor for potential reduction in efficacy. Telithromycin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of telithromycin; monitor for potential reduction in efficacy. Telithromycin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Major) Avoid concurrent administration of telithromycin and letermovir, as concomitant use may result in elevated concentrations of both drugs. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If these drugs must be administered together, consider telithromycin dose adjustment and closely monitor for adverse events, including tachycardia, atrial fibrillation, QT prolongation, hepatotoxicity, and gastrointestinal events. In vitro studies show that telithromycin may act as an inhibitor for the hepatic uptake transporters the organic anion-transporting polypeptides (OATP1B1/3); letermovir is an OATP1B1/3 substrate. Although the clinical relevance of this finding it unknown, it is possible that concomitant administration could result in increased letermovir plasma concentrations. Telithromycin is also a substrate of CYP3A4. Letermovir is moderate CYP3A4 inhibitor; however when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In drug interaction studies, concurrent administration with other strong CYP3A4 inhibitors increased the maximum plasma concentration (Cmax) and exposure (AUC) of telithromycin by up to 55% and 95%, respectively.
    Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Levalbuterol: (Minor) Use caution if short-acting beta-agonists are administered with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levamlodipine: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Levofloxacin: (Moderate) Levofloxacin should be used cautiously with telithromycin as concurrent use may increase the risk for QT prolongation. Telithromycin and levofloxacin have been associated with QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Levoketoconazole: (Major) Avoid concurrent administration of ketoconazole and telithromycin. Coadministration results in elevated plasma concentrations of telithromycin and an increased risk for adverse events. A multi-dose interaction study found coadministration resulted in an increase of the Cmax and AUC of telithromycin by 51% and 95%, respectively. In addition, use of these drugs together may increase the risk for QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP); ketoconazole can also prolong the QT interval.
    Levomethadyl: (Contraindicated) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes. Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval, including telithromycin.
    Levomilnacipran: (Major) The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Telithromycin is considered a strong inhibitor of CYP3A4. Levomilnacipran is partially metabolized by CYP3A4, and decreased metabolism of the drug can lead to an increased risk of adverse effects such as urinary retention.
    Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Lidocaine: (Moderate) Telithromycin, a ketolide antibiotic, can compete with lidocaine for metabolism by CYP3A4. This can result in increased systemic concentrations of lidocaine if the two drugs are coadministered.
    Lidocaine; Prilocaine: (Moderate) Telithromycin, a ketolide antibiotic, can compete with lidocaine for metabolism by CYP3A4. This can result in increased systemic concentrations of lidocaine if the two drugs are coadministered.
    Lithium: (Moderate) Lithium should be used cautiously and with close monitoring with telithromycin as concurrent use may increase the risk of QT prolongation. Lithium has been associated with QT prolongation. Telithromycin is associated with QT prolongation and torsades de pointes (TdP).
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with telithromycin due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Telithromycin is associated with QT prolongation and TdP.
    Lomitapide: (Contraindicated) Concomitant use of telithromycin and lomitapide is contraindicated. If treatment with telithromycin is unavoidable, lomitapide should be stopped during the course of treatment. Telithromycin is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
    Lonafarnib: (Contraindicated) Coadministration of lonafarnib and telithromycin is contraindicated; concurrent use may increase the exposure of both drugs and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; telithromycin is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425%.
    Long-acting beta-agonists: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loperamide: (Moderate) Use caution when using telithromycin in combination with loperamide as concurrent use may increase the risk of QT prolongation and increased loperamide-related adverse effects. Loperamide is a CYP3A4 and P-glycoprotein (P-gp) substrate that at high doses, has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Telithromycin is a P-gp and strong CYP3A4 inhibitor that is also associated with QT prolongation and TdP.
    Loperamide; Simethicone: (Moderate) Use caution when using telithromycin in combination with loperamide as concurrent use may increase the risk of QT prolongation and increased loperamide-related adverse effects. Loperamide is a CYP3A4 and P-glycoprotein (P-gp) substrate that at high doses, has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Telithromycin is a P-gp and strong CYP3A4 inhibitor that is also associated with QT prolongation and TdP.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with telithromycin due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). (Major) Avoid coadministration of telithromycin and ritonavir due to increased telithromycin exposure which may increase the risk of QT prolongation; ritonavir exposure may also increase. Both drugs are substrates and strong inhibitors of CYP3A4.
    Lorlatinib: (Major) Avoid coadministration of lorlatinib with telithromycin due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If telithromycin is discontinued, resume the original dose of lorlatinib after 3 half-lives of telithromycin. Lorlatinib is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%.
    Lovastatin: (Contraindicated) Concurrent use of lovastatin and telithromycin is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including telithromycin. If no alternative to a short course of treatment with telithromycin is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
    Lovastatin; Niacin: (Contraindicated) Concurrent use of lovastatin and telithromycin is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including telithromycin. If no alternative to a short course of treatment with telithromycin is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
    Lumacaftor; Ivacaftor: (Major) If telithromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of telithromycin; avoid concurrent use. If concomitant use of telithromycin is necessary, monitor microbiological activity and adjust drug dosages as necessary. Lumacaftor; ivacaftor dosage adjustment is not required when telithromycin is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking telithromycin, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking telithromycin. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Telithromycin is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Although telithromycin is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A inhibitor increased ivacaftor exposure by 4.3-fold.
    Lumateperone: (Major) Avoid coadministration of lumateperone and telithromycin as concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
    Lurasidone: (Contraindicated) Concurrent use of lurasidone with strong CYP3A4 inhibitors, such as telithromycin, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Increased lurasidone plasma concentrations are expected when the drug is co-administered with inhibitors of CYP3A4.
    Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and telithromycin due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. Lurbinectedin is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as telithromycin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Macitentan: (Major) Avoid concurrent use of macitentan and telithromycin. Telithromycin is a strong inhibitor of CYP3A4. Coadminsitration of macitentan with another strong CYP3A4 inhibitor (ketoconazole) approximately doubles macitentan exposure. Consider alternative treatment options for pulmonary hypertension if treatment with telithromycin is necessary.
    Maprotiline: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with maprotiline. Telithromycin is associated with QT prolongation and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
    Maraviroc: (Major) Coadministration of maraviroc (a substrate of CYP3A, P-gp, and OATP1B1) with telithromycin (a strong CYP3A4 inhibitor and P-gp/OATP1B1 inhibitor) may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with telithromycin (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
    Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with telithromycin, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
    Mefloquine: (Major) Caution is advised during coadministration of telithromycin and mefloquine as concurrent use may increase the risk of QT prolongation and mefloquine-related adverse effects. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as telithromycin. In addition, telithromycin is a strong inhibitor of CYP3A4, and mefloquine is a CYP3A4 substrate. Coadministration may increase mefloquine systemic exposure further increasing the risk for QT prolongation.
    Meperidine; Promethazine: (Moderate) Use caution as coadministration of telithromycin and promethazine may increase the risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Metaproterenol: (Minor) Use caution if short-acting beta-agonists are administered with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Metformin; Repaglinide: (Moderate) Repaglinide is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of repaglinide with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of repaglinide.
    Metformin; Rosiglitazone: (Moderate) Monitor for an increase in rosiglitazone-related adverse effects during concomitant use with telithromycin; adjust the dose of rosiglitazone based on clinical response. Coadministration may increase the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and telithromycin is a weak CYP2C8 inhibitor.
    Metformin; Saxagliptin: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP 3A4/5 inhibitor such as telithromycin.
    Methadone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with methadone. The need to coadminister these drugs should be done with a careful assessment of treatment risks versus benefits. Telithromycin is associated with QT prolongation and TdP. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Additionally, telithromycin is a strong inhibitor of CYP3A4 and may affect the metabolism of methadone. Concurrent use may result in increased serum concentrations of methadone.
    Methylergonovine: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Methylprednisolone: (Moderate) Concurrent administration of methylprednisolone with telithromycin may result in elevated methylprednisolone plasma concentrations. Use caution and monitor for corticosteroid-related side effects if these drugs are administered together. Methylprednisolone is metabolized by the hepatic isoenzyme CYP3A4; telithromycin is a strong CYP3A4 inhibitor.
    Methysergide: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Metoprolol: (Moderate) Coadministration of metoprolol with telithromycin resulted in an increase of approximately 38% in the Cmax and AUC of metoprolol. However, there was no effect on the elimination half-life of metoprolol. The increased exposure to metoprolol in patients with heart failure may be of clinical importance.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of metoprolol with telithromycin resulted in an increase of approximately 38% in the Cmax and AUC of metoprolol. However, there was no effect on the elimination half-life of metoprolol. The increased exposure to metoprolol in patients with heart failure may be of clinical importance.
    Metronidazole: (Moderate) Concomitant use of metronidazole and telithromycin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Midazolam: (Moderate) Concomitant administration of telithromycin with midazolam results in increases in the AUC of midazolam. This interaction is due to decreased midazolam metabolism through telithromycin-induced CYP3A4-inhibition. Patients should be monitored and dosage adjustment of midazolam should be considered if necessary.
    Midostaurin: (Major) Avoid the concomitant use of midostaurin and telithromycin due to the risk of increased midostaurin exposure which may increase the incidence and severity of adverse reactions; concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). If concomitant use cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity, particularly during the first week of midostaurin therapy for those with systemic mastocytosis/mast cell leukemia and during the first week of each cycle for those with acute myeloid leukemia. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Midostaurin is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration of one strong CYP3A4 inhibitor with a single dose of midostaurin increased the exposure of midostaurin and its active metabolites CGP62221 and CGP52421 by 10.4-fold, 3.5-fold, and 1.2-fold, respectively. Coadministration of another strong CYP3A4 inhibitor with twice daily doses of midostaurin increased Day 28 trough concentrations of midostaurin, CGP62221, and CGP52421 by 2.1-fold, 1.2-fold, and 1.3-fold respectively compared with day 21 trough levels with midostaurin alone.
    Mifepristone: (Major) Avoid coadministration of mifepristone with telithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving telithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with telithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with telithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with telithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with telithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and telithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Mirtazapine: (Moderate) Use caution when using mirtazapine in combination with telithromycin as concurrent use may increase the risk of QT prolongation and mirtazapine-related adverse effects. Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and TdP. Mirtazapine is a CYP3A4 substrate that has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation.
    Mitotane: (Major) Avoid the concomitant use of mitotane with telithromycin due to decreased telithromycin exposure and possible decreases in efficacy. Mitotane is a strong CYP3A4 inducer and telithromycin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of telithromycin. During administration of telithromycin and another strong CYP3A inducer, rifampin, in repeated doses, the Cmax and AUC of telithromycin were decreased by 79% and 86%, respectively.
    Mobocertinib: (Major) Avoid concomitant use of mobocertinib and telithromycin. Concomitant use increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may increase mobocertinib exposure and the risk for mobocertinib-related adverse reactions. Mobocertinib is a CYP3A substrate and telithromycin is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%.
    Modafinil: (Major) Concomitant administration of CYP3A4 inducers, such as modafinil, are expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy. In addition, telithromycin is a competitive substrate and inhibitor of CYP3A4; coadministration of telithromycin with other drugs metabolized by CYP3A4, such as modafinil, may result in increased plasma concentrations and an increase of therapeutic or adverse effects.
    Mometasone: (Moderate) Concomitant administration of telithromycin and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with telithromycin long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor.
    Moxifloxacin: (Major) Concurrent use of telithromycin and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Telithromycin is associated with QT prolongation and TdP. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Naloxegol: (Contraindicated) Concomitant use of naloxegol with telithromycin is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as telithromycin, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
    Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with telithromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Telithromycin is a strong CYP3A4 inhibitor and a weak inhibitor of CYP2C8. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was also inhibited by another inhibitor of CYP2C8.
    Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid coadministration of sirolimus with telithromycin as concurrent use may increase sirolimus exposure and risk of toxicity. Alternative agents with lesser interaction potential with sirolimus should be considered. Sirolimus is a CYP3A and P-gp substrate and telithromycin is a strong CYP3A and P-gp inhibitor. Concomitant use of another strong CYP3A and P-gp inhibitor increased sirolimus overall exposure by 10.9-fold.
    Naproxen; Esomeprazole: (Minor) Concentrations of esomeprazole may be increased with concomitant use of telithromycin. Esomeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Nebivolol; Valsartan: (Minor) Valsartan is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of valsartan with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of valsartan.
    Nefazodone: (Moderate) Concentrations of telithromycin and nefazodone may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Patients should be monitored for increased side effects.
    Nelfinavir: (Moderate) Concentrations of telithromycin and nelfinavir may be increased with coadministration, as both agents are CYP3A4 substrates and inhibitors. Additionally, nelfinavir is a substrate for P-glycoprotein (PGP) and telithromycin is a potential PGP inhibitor. Patients should be monitored for increased side effects.
    Neratinib: (Major) Avoid concomitant use of telithromycin with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
    Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are metabolized through CYP3A4 such as telithromycin since the plasma concentrations can increase; the inhibitory effect on CYP3A4 can last for multiple days. In addition, netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor such as telithromycin can significantly increase the systemic exposure to netupitant. No dosage adjustment is necessary for single dose administration of netupitant; palonosetron.
    Nevirapine: (Moderate) Telithromycin is a potent inhibitor of CYP3A4 and is expected to compete with nevirapine for metabolism; administer together with caution, with careful monitoring of the patients nevirapine plasma concentrations and HIV status.
    Niacin; Simvastatin: (Contraindicated) Telithromycin is contraindicated during simvastatin therapy. Telithromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, therapy with simvastatin must be suspended during telithromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin. Pharmacokinetic studies have reported increased simvastatin concentrations due to CYP3A4 inhibition by telithromycin. When the two drugs were coadministered, there was a 5.3-fold increase in simvastatin Cmax, an 8.9-fold increase in the AUC, a 15-fold increase in the active metabolite Cmax, and a 12-fold increase in the active metabolite AUC. In another study, when simvastatin and telithromycin were administered 12 hours apart, there was a 3.4-fold increase in simvastatin Cmax, a 4-fold increase in AUC, a 3.2-fold increase in the active metabolite Cmax, and a 4.3-fold increase in the active metabolite AUC. Increased serum concentrations of HMG-CoA reductase inhibitors are associated with myopathy. Additionally, simvastatin is a substrate for organic anion transport protein (OATP) and telithromycin may act as an inhibitor for the hepatic organic anion transport protein (OATP) uptake transporters OATP1B1 and OATP1B3.
    Nicardipine: (Moderate) Telithromycin, a ketolide antibiotic, can theoretically compete with nicardipine for metabolism by CYP3A4. This can result in increased concentrations of nicardipine if the two drugs are coadministered.
    Nifedipine: (Moderate) Telithromycin, a ketolide antibiotic, can theoretically compete with nifedipine for metabolism by CYP3A4. This can result in increased concentrations of nifedipine if the two drugs are coadministered.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and telithromycin; significant prolongation of the QT interval may occur. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Telithromycin is also associated with QT prolongation and torsade de pointes (TdP). If therapy with telithromycin is necessary, interrupt nilotinib therapy if possible. Monitor closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in adult patients with resistant or intolerant Ph+ CML or to 200 mg once daily in adult patients with newly diagnosed Ph+ CML. If telithromycin is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and telithromycin is a strong inhibitor of CYP3A4.
    Nimodipine: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as nimodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as telithromycin, are expected to increase the exposure and clinical effect of nintedanib. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Telithromycin is a potent CYP3A4 inhibitor and a mild inhibitor of P-gp; nintedanib is a P-gp substrate and a minor CYP3A4 substrate. In drug interactions studies, administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%.
    Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of telithromycin and ritonavir due to increased telithromycin exposure which may increase the risk of QT prolongation; ritonavir exposure may also increase. Both drugs are substrates and strong inhibitors of CYP3A4.
    Nisoldipine: (Moderate) Telithromycin, a ketolide antibiotic, can theoretically compete with nisoldipine for metabolism by CYP3A4. This can result in increased concentrations of nisoldipine if the two drugs are coadministered.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Norfloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with norfloxacin. Telithromycin is associated with QT prolongation and TdP. Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Octreotide: (Moderate) Use octreotide with caution in combination with telithromycin. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Moderate) Ofloxacin should be used cautiously with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin and quinolones are associated with QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with olanzapine. Telithromycin is associated with QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Olanzapine; Fluoxetine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with olanzapine. Telithromycin is associated with QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. (Moderate) Use fluoxetine with caution in combination with telithromycin. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Telithromycin is also associated with QT prolongation and TdP.
    Olanzapine; Samidorphan: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with olanzapine. Telithromycin is associated with QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Olaparib: (Major) Avoid coadministration of olaparib with telithromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after telithromycin is discontinued. Olaparib is a CYP3A substrate and telithromycin is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
    Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and telithromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and telithromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If telithromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Olodaterol: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of telithromycin and ritonavir due to increased telithromycin exposure which may increase the risk of QT prolongation; ritonavir exposure may also increase. Both drugs are substrates and strong inhibitors of CYP3A4. (Major) Concurrent administration of telithromycin with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of both drugs and subsequent adverse effects. There may be a risk of QT prolongation when these drugs are administered together. While dasabuvir; ombitasvir; paritaprevir; ritonavir and ombitasvir; paritaprevir; ritonavir did not prolong the QT interval to a clinically relevant extent in healthy subjects, ritonavir has been associated with dose-related QT prolongation in other trials. Telithromycin also has the potential to cause QT prolongation. Both ritonavir and telithromycin are substrates and potent inhibitors of the hepatic isoenzyme CYP3A4; paritaprevir and dasabuvir (minor) are CYP3A4 substrates. In addition, telithromycin inhibits the drug transporter P-glycoprotein (P-gp); dasabuvir, ombitasvir, paritaprevir and ritonavir are all substrates of P-gp. Telithromycin also inhibits the organic anion transporting polypeptides (OATP). Paritaprevir is a substrate of OATP1B1 and OATP1B3. Caution and close monitoring is advised if these drugs are administered together.
    Omeprazole: (Minor) Concentrations of omeprazole may be increased with concomitant use of telithromycin. Omeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Omeprazole; Amoxicillin; Rifabutin: (Minor) Concentrations of omeprazole may be increased with concomitant use of telithromycin. Omeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Omeprazole; Sodium Bicarbonate: (Minor) Concentrations of omeprazole may be increased with concomitant use of telithromycin. Omeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Ondansetron: (Major) Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Telithromycin is associated with a lower, but possible risk for QT prolongation and TdP.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Oritavancin: (Moderate) Telithromycin is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of telithromycin may be reduced if these drugs are administered concurrently.
    Osilodrostat: (Major) Reduce the dose of osilodrostat by one-half and consider more frequent ECG monitoring during coadministration of telithromycin; concurrent use may increase osilodrostat exposure and the risk of osilodrostat-related adverse reactions, including QT prolongation. Osilodrostat is a CYP3A4 substrate that is associated with dose-dependent QT prolongation; telithromycin is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval.
    Osimertinib: (Major) Avoid coadministration of telithromycin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Telithromycin is associated with QT prolongation and TdP.
    Ospemifene: (Moderate) Coadministration of telithromycin and ospemifene may increase ospemifene systemic concentrations and increase the risk of ospemifene-related adverse reactions. Telithromycin is a strong CYP3A4 inhibitor, and ospemifene is a CYP3A4 substrate. Strong CYP3A4 inhibitors increase the systemic exposure of ospemifene by approximately1.4-fold.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of telithromycin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxcarbazepine: (Major) Oxcarbazepine and its active metabolite, MHD, are dose-dependent inducers of the hepatic CYP3A4 isoenzyme thereby having the potential to lower the plasma levels of medications metabolized through these pathways, such a telithromycin.
    Oxybutynin: (Moderate) Concentrations of oxybutynin may be increased with concomitant use of telithromycin. Oxybutynin is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of telithromycin is necessary. If telithromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like telithromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If telithromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking telithromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Telithromycin is associated with QT prolongation and TdP.
    Paclitaxel: (Moderate) Concentrations of paclitaxel may be increased with concomitant use of telithromycin. Paclitaxel is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Caution is warranted if these drugs are coadministered.
    Palbociclib: (Major) Avoid coadministration of telithromycin with palbociclib; significantly increased palbociclib exposure may occur. If concomitant use cannot be avoided, reduce the dose of palbociclib to 75 mg PO once daily and monitor for increased adverse reactions. If telithromycin is discontinued, increase the palbociclib dose (after 3 to 5 half-lives of telithromycin) to the dose used before initiation of telithromycin. Palbociclib is primarily metabolized by CYP3A4 and telithromycin is a strong CYP3A4 inhibitor. In a drug interaction trial, coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of palbociclib by 87% and 34%, respectively.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Telithromycin has been associated with QT prolongation and TdP. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) The co-administration of panobinostat with telithromycin is not recommended; QT prolongation has been reported with both agents. If concomitant use cannot be avoided, reduce the panobinostat dose from 20 mg PO to 10 mg PO and closely monitor electrocardiograms during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Telithromycin is a strong CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor.
    Paricalcitol: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as telithromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Pasireotide: (Moderate) Use caution when using pasireotide in combination with telithromycin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Telithromycin is associated with QT prolongation and torsades de pointes (TdP).
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and telithromycin have been reported to prolong the QT interval. If pazopanib and telithromycin must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp). Telithromycin is an inhibitor of CYP3A4 and P-gp. Concurrent administration of telithromycin and pazopanib may result in increased pazopanib concentrations; avoid use of these agents together if possible. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur.
    Pemigatinib: (Major) Avoid coadministration of pemigatinib and telithromycin due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If telithromycin is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of telithromycin. Pemigatinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%.
    Pentamidine: (Major) Telithromycin has the potential to prolong the QT interval and should be used cautiously in combination with other drugs that may also prolong the QT interval, including pentamidine. Pentamidine has been associated with QT prolongation.
    Perampanel: (Moderate) Concurrent use of perampanel with telithromycin may increase exposure to perampanel and increase plasma concentrations. Telithromycin is a potent inhibitor of CYP3A4, an enzyme responsible for perampanel metabolism. Monitor patients for increases in adverse effects such as anger, anxiety, irritability, somnolence, dizziness, or nausea. Dose adjustment may be required.
    Pergolide: (Major) Coadministration of telithromycin and ergot alkaloids is not recommended due to the potential for ergot toxicity. Although no specific drug interaction studies have been performed with telithromycin, drug interactions have been reported with macrolide antibiotics. Concomitant administration of ergot alkaloids with macrolides resulted in acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
    Perindopril; Amlodipine: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as amlodipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Perphenazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with perphenazine. Telithromycin is associated with QT prolongation and TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    Perphenazine; Amitriptyline: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with perphenazine. Telithromycin is associated with QT prolongation and TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    Pexidartinib: (Major) Avoid coadministration of pexidartinib with telithromycin as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If telithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of telithromycin. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Phenobarbital: (Major) Concomitant administration of a CYP3A4 inducer, such as phenobarbital, with telithromycin is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant administration of a CYP3A4 inducer, such as phenobarbital, with telithromycin is expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Phentermine; Topiramate: (Moderate) Caution is warranted when topiramate is administered with telithromycin as there is a potential for decreased telithromycin concentrations and loss of efficacy. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Telithromycin is a substrate of CYP3A4.
    Phenytoin: (Major) Concomitant administration of CYP3A4 inducers such as phenytoin, are expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy of telithromycin.
    Pimavanserin: (Major) Coadministration of pimavanserin and telithromycin should be avoided if possible. Telithromycin is associated with a possible risk for QT prolongation and torsade de pointes (TdP); pimavanserin may also cause QT prolongation. In addition, pimavanserin is primarily metabolized by CYP3A4 and CYP3A5. Concurrent use of a strong inhibitor of CYP3A4, such as telithromycin, is expected to increase pimavanserin exposure. If coadministration cannot be avoided, reduce the pimavanserin dose to 10 mg/day PO and closely monitor for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
    Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of telithromycin with pimozide is contraindicated.
    Pirbuterol: (Minor) Use caution if short-acting beta-agonists are administered with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Pitavastatin: (Major) Pitavastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of pitavastatin with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of pitavastatin.
    Pitolisant: (Major) Avoid coadministration of pitolisant with telithromycin as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of telithromycin due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; telithromycin is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
    Ponatinib: (Major) Avoid coadministration of ponatinib and telithromycin due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of telithromycin and consider alternative therapy. After telithromycin has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting telithromycin. Ponatinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking telithromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Telithromycin is associated with QT prolongation and TdP.
    Posaconazole: (Contraindicated) Concurrent use of posaconazole and telithromycin is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Both posaconazole and telithromycin are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of telithromycin. Further, telithromycin is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and telithromycin. Additionally, both posaconazole and telithromycin have been associated with prolongation of the QT interval as well as TdP.
    Pralsetinib: (Major) Avoid coadministration of telithromycin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. After telithromycin has been discontinued for 3 to 5 elimination half-lives, resume the pralsetinib dose taken prior to initiating telithromycin. Pralsetinib is a CYP3A and P-glycoprotein (P-gp) substrate and telithromycin is a combined P-gp and strong CYP3A inhibitor. Coadministration with another combined P-gp and strong CYP3A inhibitor increased the AUC of pralsetinib by 251%.
    Pravastatin: (Major) Pravastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of pravastatin with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of pravastatin.
    Prednisolone: (Moderate) Concentrations of prednisolone may be increased with concomitant use of telithromycin. Prednisolone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Prednisone: (Moderate) Increased prednisone active metabolite concentrations are expected with telithromycin coadministration. Prednisone is metabolized by the liver to the active metabolite prednisolone through the 11b-hydroxydehydrogenase enzyme (which is not part of the CYP system). Prednisolone is metabolized by the CYP3A4-mediated 6b-hydroxylase enzyme to inactive compounds. Telithromycin is a known inhibitor of CYP3A4, and prednisolone is a CYP3A4 substrate. Additionally, prednisone is a substrate of P-glycoprotein (PGP) and telithromycin may be a PGP inhibitor. Monitor patients for corticosteroid-related side effects if both prednisone and telithromycin are taken.
    Primaquine: (Moderate) Caution is advised with coadministration of telithromycin and primaquine as concurrent use may increase the risk of QT prolongation. Primaquine has potential to prolong the QT interval; telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Primidone: (Major) Concomitant administration of CYP3A4 inducers such as primidone, which is metabolized to phenobarbital, are expected to cause subtherapeutic concentrations of telithromycin and loss of efficacy.
    Probenecid; Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and telithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Telithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken telithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Procainamide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with procainamide. Both telithromycin and procainamide are associated with QT prolongation and TdP.
    Prochlorperazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with prochlorperazine. Telithromycin is associated with QT prolongation and TdP. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Progesterone: (Moderate) Use caution if coadministration of telithromycin with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Telithromycin is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
    Promethazine: (Moderate) Use caution as coadministration of telithromycin and promethazine may increase the risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Promethazine; Dextromethorphan: (Moderate) Use caution as coadministration of telithromycin and promethazine may increase the risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Promethazine; Phenylephrine: (Moderate) Use caution as coadministration of telithromycin and promethazine may increase the risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation. Telithromycin is associated with QT prolongation and TdP.
    Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with propafenone. Telithromycin is associated with QT prolongation and TdP. Propafenone, a Class IC antiarrhythmic, also increases the QT interval, but largely due to prolongation of the QRS interval. Additionally, telithromycin is a strong inhibitor of CYP3A4 and may affect the CYP3A4 metabolism of propafenone. This could potentially result in increased plasma concentrations of propafenone.
    Quazepam: (Moderate) Quazepam is metabolized by oxidative metabolism which may be inhibited by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response.
    Quetiapine: (Major) Concurrent use of quetiapine and telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both telithromycin and quetiapine are associated with a risk for QT prolongation. In addition, the cytochrome P450 3A4 (CYP3A4) isoenzyme is involved in the metabolism of quetiapine. It is recommended to reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events when used with a potent CYP inhibitor, such as telithromycin. If telithromycin is discontinued, increase the quetiapine dose by 6-fold.
    Quinidine: (Major) Concurrent use of quinidine and/or quinidine-containing products (e.g., dextromethorphan; quinidinne) with telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The manufacturer of dextromethorphan; quinidine recommends an initial ECG evaluation (baseline and 3 to 4 hours post-dose) in patients taking dextromethorphan; quinidine in combination with moderate or strong CYP3A4 inhibitors such as telithromycin. The quinidine component of dextromethorphan; quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of dextromethorphan; quinidine with moderate or strong CYP3A4 inhibitors may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects. In addition, telithromycin has the potential to prolong the QTc interval in some patients.
    Quinine: (Major) Concurrent use of quinine with telithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and telithromycin have been associated with prolongation of the QT interval. In addition, because both telithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Ramelteon: (Moderate) Concentrations of ramelteon may be increased with concomitant use of telithromycin. Ramelteon is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Ranolazine: (Contraindicated) Coadministration of ranolazine with telithromycin is contraindicated as concurrent use may increase ranolazine exposure; additive effects on the QT interval are also possible. Ranolazine is a CYP3A4 substrate that is associated with dose- and plasma concentration-related increases in the QTc interval. Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and TdP. Coadministration of another strong CYP3A4 inhibitor increased ranolazine exposure by 220%.
    Red Yeast Rice: (Contraindicated) The concurrent use of telithromycin with red yeast rice is not recommended. Pharmacokinetic studies have reported increased simvastatin concentrations due to CYP3A4 inhibition by telithromycin. When the two drugs were co-administered, there was a 5.3-fold increase in simvastatin Cmax, an 8.9-fold increase in the AUC, a 15-fold increase in the active metabolite Cmax, and a 12-fold increase in the active metabolite AUC. In another study, when simvastatin and telithromycin were administered 12 hours apart, there was a 3.4-fold increase in simvastatin Cmax, a 4-fold increase in AUC, a 3.2-fold increase in the active metabolite Cmax, and a 4.3-fold increase in the active metabolite AUC. Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with telithromycin.
    Regorafenib: (Major) Avoid coadministration of regorafenib with telithromycin due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each.
    Relugolix: (Major) Avoid concomitant use of relugolix and oral telithromycin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer telithromycin at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of telithromycin is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Telithromycin is a P-gp inhibitor that is also associated with QT prolongation and torsade de pointes (TdP).
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral telithromycin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer telithromycin at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of telithromycin is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Telithromycin is a P-gp inhibitor that is also associated with QT prolongation and torsade de pointes (TdP). (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. The pharmacokinetics of ethinyl estradiol were not altered when low dose triphasic oral contraceptives containing ethinyl estradiol; levonorgestrel were administered to women of child-bearing potential also receiving telithromycin. Plasma concentrations of levonorgestrel were increased by telithromycin. Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include telithromycin.
    Repaglinide: (Moderate) Repaglinide is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1. Coadministration of repaglinide with inhibitors of OATP, such as telithromycin may theoretically result in increased concentrations of repaglinide.
    Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as telithromycin, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
    Revefenacin: (Major) Coadministration of revefenacin is not recommended with telithromycin because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; telithromycin is an inhibitor of OATP1B1 and OATP1B3.
    Ribociclib: (Major) Avoid coadministration of ribociclib with telithromycin due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of both drugs may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a CYP3A4 substrate and strong inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Telithromycin is also a CYP3A4 substrate and strong inhibitor that has been associated with QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with telithromycin due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of both drugs may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a CYP3A4 substrate and strong inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Telithromycin is also a CYP3A4 substrate and strong inhibitor that has been associated with QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Rifampin: (Contraindicated) Concomitant use of telithromycin and rifampin, a potent CYP3A4 inducer, should be avoided. During administration in repeated doses, the Cmax and AUC of t