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  • CLASSES

    Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)s

    DEA CLASS

    Rx

    DESCRIPTION

    Non-nucleoside reverse transcriptase inhibitor (NNRTI)
    Used with other antiretroviral drugs to treat HIV infection in patients 16 years and older
    May cause drug-induced rashes

    COMMON BRAND NAMES

    Rescriptor

    HOW SUPPLIED

    Rescriptor Oral Tab: 100mg, 200mg

    DOSAGE & INDICATIONS

    For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents.
    Oral dosage
    Adults

    400 mg PO 3 times daily.

    Adolescents 16 years and older

    400 mg PO 3 times daily.

    MAXIMUM DOSAGE

    Adults

    1200 mg/day PO.

    Elderly

    1200 mg/day PO.

    Adolescents

    >= 16 years: 1200 mg/day PO.
    < 16 years: Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosing in patients with hepatic impairment has not been studied.

    Renal Impairment

    Dosing in patients with renal impairment has not been studied.

    ADMINISTRATION

    Oral Administration

    Administer orally with or without food.
    Instruct patients with achlorhydria to take the tablets with an acidic beverage to aid in absorption (e.g., orange or cranberry juice).
    Administer at least 1 hour before or after didanosine or antacids.
    The 100 mg tablets may be dispersed in water prior to administration. To prepare a dispersion, add four (4) 100 mg tablets to at least 3 ounces of water, allow to stand for a few minutes, and then stir until a uniform dispersion occurs. Administer immediately, then instruct the patient to rinse the glass and swallow the rinse to ensure the entire dose is given.
    The 200 mg tablets, which are about one-third smaller than the 100 mg tablets, should be taken as intact tablets because they are not readily dispersed in water.

    STORAGE

    Rescriptor:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Unplanned antiretroviral therapy interruption may be necessary in specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., < 1—2 days) is necessary, in general it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption is because of serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered. When the antiretroviral regimen contains drugs with differing half-lives, stopping all drugs simultaneously may result in functional monotherapy of the drug with the longest half-life. For example, after discontinuation, the duration of detectable drug concentrations of efavirenz and nevirapine range from < 1 week to > 3 weeks. Simultaneously stopping all drugs in a regimen containing these agents may result in functional monotherapy with the NNRTI and may increase the risk of NNRTI-resistant mutations. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.

    Hepatic disease

    Delavirdine is primarily metabolized by the liver. Use cautiously in patients with hepatic disease.

    Pregnancy

    Antiretroviral prophylaxis should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Delavirdine is classified as FDA pregnancy risk category C. In clinical trials and during the post-marketing period of delavirdine, nine unplanned pregnancies occurred with ten infants born (one set of twins). Of these ten infants, eight were born healthy, one was born HIV-positive but without congenital abnormalities, and one was born prematurely with a small muscular ventricular septal defect to a patient who received approximately 6-weeks of treatment with delavirdine and zidovudine early in the course of pregnancy. Studies in rodents indicate there is the potential for teratogenicity and developmental toxicity. Given the minimal human data, along with the concerns regarding teratogenicity, delavirdine is not recommended for use during pregnancy unless no other alternatives are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; if there is detectable viremia, perform resistance testing. For women not currently receiving antiretroviral therapy when the pregnancy is recognized, determination of treatment should be based on the same parameters used for non-pregnant patients (including resistance testing prior to treatment). Initiate treatment as soon as possible in women who require immediate treatment for their own health. Consideration can be given to delaying therapy after the 1st trimester in mothers receiving therapy solely for the prevention of perinatal transmission; however, earlier initiation of therapy may be more effective in reducing in utero transmission. For women not currently receiving treatment, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing prior to initiating therapy. Zidovudine should be included in the antenatal treatment regimen unless there is severe toxicity associated with use or documented resistance. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit and at least every 3 months; monitor plasma HIV RNA at the initial visit, 2 to 6 weeks after initiating/changing therapy, monthly until undetectable, and then at least every 2 months, and at 34 to 36 weeks gestation. Perform antiretroviral resistance testing in the presence of persistently detectable HIV RNA despite antiretroviral receipt; assess patient adherence and consult an HIV treatment expert to guide changes in therapy. Given the limited data on the effect of combination therapy on the fetus, second trimester ultrasound to assess fetal anatomy may be prudent in women who received antiretroviral therapy during the first trimester (particularly if the regimen included efavirenz). Perform standard glucose screening in women receiving antiretroviral therapy, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. If a woman decides to discontinue therapy, a planned treatment interruption, taking into account the specific pharmacokinetic and administration parameters of each drug, should occur to avoid true or functional monotherapy and the development of resistance. It is strongly recommended that health care providers report cases of antenatal antiretroviral drug exposure to the Antiretroviral Pregnancy Registry; telephone 800—258—4263; fax 800—800—1052; the Antiretroviral Pregnancy Registry is also accessible via the Internet.

    Children, infants, neonates

    The safety and efficacy of delavirdine in neonates, infants, children, and adolescents < 16 years of age have not been determined.

    Breast-feeding

    To reduce the risk of postnatal transmission, HIV-infected mothers within the United States are advised by the Centers for Disease Control and Prevention to avoid breast-feeding. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy, including delavirdine. If an HIV-infected mother opts to breast-feed, the infant should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, health care workers may contact the Perinatal HIV Hotline (888-448-8765).[42452] There are limited data regarding the use of delavirdine during breast-feeding and excretion into human breast milk is unknown. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.

    Exfoliative dermatitis

    Patients receiving delavirdine should be observed for the development of severe rash (e.g., exfoliative dermatitis) or rash accompanied by symptoms such as fever, blistering, oral lesions, conjunctivitis, edema, and/or myalgia or arthralgia. Patients who develop these symptoms should discontinue treatment with delavirdine. Severe rashes including erythema multiforme and Stevens-Johnson syndrome have been reported.

    Achlorhydria

    Patients with achlorhydria should take delavirdine with an acidic beverage (e.g., orange or cranberry juice). However, the effect of an acidic beverage on the absorption of delavirdine in patients with achlorhydria has not been investigated.

    Human immunodeficiency virus (HIV) infection resistance

    Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. In high-income countries (e.g., US, some European countries, Australia, Japan), approximately 10% to 17% of treatment-naive individuals have resistance mutations to at least 1 antiretroviral drug; up to 8% (but generally less than 5%) of transmitted viruses will exhibit resistance to drugs from more than 1 class. Therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. As with all other antiretroviral agents, resistance can develop when delavirdine is used either alone or in combination with other agents. Monotherapy with delavirdine is not recommended. There is also the possibility that delavirdine may induce a cross-resistance to other non-nucleoside reverse transcriptase inhibitors.

    Autoimmune disease, Graves' disease, Guillain-Barre syndrome, immune reconstitution syndrome

    Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to delavirdine therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.

    Hepatitis, hepatitis B and HIV coinfection

    Perform hepatitis B virus (HBV) screening in any patient who presents with HIV-infection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide with emtricitabine or tenofovir disoproxil fumarate in combination with either lamivudine or emtricitabine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still requires treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.

    Hepatitis C and HIV coinfection

    HIV treatment guidelines recommend all patients presenting with HIV infection undergo testing for hepatitis C, with continued annual screening advised for those persons considered high risk for acquiring hepatitis C. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. For most patients, the benefits of concurrent therapy outweighs the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    erythema multiforme / Delayed / 0-1.0
    hepatic failure / Delayed / 0-1.0
    hemolytic anemia / Delayed / 0-1.0
    rhabdomyolysis / Delayed / 0-1.0
    renal failure (unspecified) / Delayed / 0-1.0
    vasculitis / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    laryngospasm / Rapid / Incidence not known
    pancytopenia / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known
    epididymitis / Delayed / Incidence not known

    Moderate

    erythema / Early / 16.7-16.7
    depression / Delayed / 4.9-12.6
    elevated hepatic enzymes / Delayed / 1.8-5.1
    skin ulcer / Delayed / 4.4-4.4
    hyperamylasemia / Delayed / 2.5-2.9
    hyperbilirubinemia / Delayed / 1.7-2.5
    hyperglycemia / Delayed / 0.8-1.7
    hypoglycemia / Early / 0.8-1.7
    bullous rash / Early / Incidence not known
    dysphagia / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    fecal incontinence / Early / Incidence not known
    colitis / Delayed / Incidence not known
    sialadenitis / Delayed / Incidence not known
    lipodystrophy / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    hallucinations / Early / Incidence not known
    migraine / Early / Incidence not known
    mania / Early / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    amnesia / Delayed / Incidence not known
    euphoria / Early / Incidence not known
    impaired cognition / Early / Incidence not known
    confusion / Early / Incidence not known
    hyperreflexia / Delayed / Incidence not known
    hyperesthesia / Delayed / Incidence not known
    hypertonia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    candidiasis / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hypophosphatemia / Delayed / Incidence not known
    tetany / Early / Incidence not known
    synovitis / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    blepharitis / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    blurred vision / Early / Incidence not known
    proteinuria / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known

    Mild

    rash / Early / 35.4-35.4
    nausea / Early / 14.7-20.3
    headache / Early / 11.2-16.8
    pruritus / Rapid / 16.7-16.7
    fatigue / Early / 5.3-16.0
    asthenia / Delayed / 5.3-16.0
    maculopapular rash / Early / 14.3-14.3
    infection / Delayed / 1.2-7.6
    influenza / Delayed / 2.4-7.3
    sinusitis / Delayed / 1.2-7.3
    fever / Early / 1.6-7.1
    anxiety / Delayed / 2.4-6.7
    vomiting / Early / 2.5-6.5
    diarrhea / Early / 2.4-5.9
    abdominal pain / Early / 2.4-5.0
    insomnia / Early / 1.2-5.0
    cough / Delayed / 3.5-5.0
    pharyngitis / Delayed / 1.6-5.0
    vesicular rash / Delayed / 4.4-4.4
    urticaria / Rapid / Incidence not known
    alopecia / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    seborrhea / Delayed / Incidence not known
    folliculitis / Delayed / Incidence not known
    diaphoresis / Early / Incidence not known
    skin discoloration / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    polydipsia / Early / Incidence not known
    xerostomia / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    gingivitis / Delayed / Incidence not known
    gastroesophageal reflux / Delayed / Incidence not known
    weight gain / Delayed / Incidence not known
    anorexia / Delayed / Incidence not known
    dyspepsia / Early / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    eructation / Early / Incidence not known
    flatulence / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    Cushingoid features / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    chills / Rapid / Incidence not known
    malaise / Early / Incidence not known
    pallor / Early / Incidence not known
    weakness / Early / Incidence not known
    agitation / Early / Incidence not known
    emotional lability / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    paranoia / Early / Incidence not known
    dizziness / Early / Incidence not known
    tremor / Early / Incidence not known
    rhinitis / Early / Incidence not known
    epistaxis / Delayed / Incidence not known
    hiccups / Early / Incidence not known
    ecchymosis / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    parosmia / Delayed / Incidence not known
    xerophthalmia / Early / Incidence not known
    otalgia / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    diplopia / Early / Incidence not known
    polyuria / Early / Incidence not known
    amenorrhea / Delayed / Incidence not known
    nocturia / Early / Incidence not known

    DRUG INTERACTIONS

    Abemaciclib: (Major) If coadministration with delavirdine 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 delavirdine is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of delavirdine. Abemaciclib is a CYP3A4 substrate and delavirdine 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 delavirdine; significantly increased acalabrutinib exposure may occur. Acalabrutinib is a CYP3A4 substrate; delavirdine 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; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with delavirdine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of delavirdine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Acetaminophen; Dextromethorphan: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of delavirdine is necessary. If delavirdine 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 delavirdine 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 delavirdine 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.
    Acetaminophen; Propoxyphene: (Major) Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and propoxyphene is not recommended. Propoxyphene is a substrate and an inhibitor of CYP3A4. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP3A4 inhibitor, such as delavirdine. A reduced dosage of propoxyphene may be needed. Monitor patients for central nervous system (CNS) and respiratory depression.
    Acetaminophen; Tramadol: (Moderate) Since tramadol is primarily metabolized by cytochrome P450 isoenzyme CYP2D6, agents that inhibit this enzyme, such as delavirdine, decrease the metabolism of tramadol. Concomitant use of these agents and tramadol may increase plasma levels of tramadol and decrease concentration of the active metabolite leading to decreased analgesic effects and possibly increased side effects due to higher tramadol concentrations.
    Adefovir: (Major) Patients who are concurrently taking adefovir with non-nucleoside reverse transcriptase inhibitors are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
    Ado-Trastuzumab emtansine: (Major) Avoid coadministration of delavirdine 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 delavirdine has cleared from the circulation (approximately 3 half-lives of delavirdine) 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; delavirdine is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
    Alfentanil: (Major) Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19.Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of alfentanil, a CYP substrate may be noted.
    Alfuzosin: (Severe) Alfuzosin is contraindicated for use with delavirdine due to the potential for serious/life-threatening reactions, including hypotension. Coadministration is expected to reduce the metabolism and increase systemic exposure to alfuzosin. Alfuzosin is primarily metabolized by CYP3A4; delavirdine is a strong inhibitor of this enzyme. Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
    Aliskiren; Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with delavirdine is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and delavirdine should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
    Alosetron: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as alosetron, should be expected with concurrent use of delavirdine.
    Alprazolam: (Severe) According to the manufacturer of delavirdine, coadministration of alprazolam and delavirdine is contraindicated. Delavirdine is a potent CYP3A4 inhibitor. The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome CYP3A. Drugs that inhibit this metabolic pathway may profoundly decrease alprazolam clearance, resulting in increased potential for serious alprazolam-related adverse events, such as respiratory depression and prolonged sedation.
    Amiodarone: (Major) Delavirdine is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. Coadministration of delavirdine with amiodarone should be done with caution. Therapeutic monitoring of amiodarone concentrations is recommended.
    Amitriptyline: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Amitriptyline; Chlordiazepoxide: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine. (Moderate) Delavirdine is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
    Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Atorvastatin: (Major) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Coadminister delavirdine and atorvastatin cautiously; use the lowest possible dose of atorvastatin. Delavirdine is a potent inhibitor of CYP3A4. Atorvastatin is a substrate of CYP3A4. If these drugs are coadministered, carefully monitor the patient. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes. (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Benazepril: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Olmesartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Telmisartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Valsartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Amoxapine: (Moderate) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme; however, specific interaction studies have not been performed. Caution is recommended when administering delavirdine with CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions. Affected agents may include amoxapine. A dosage adjustment of amoxapine may be needed when given concurrently with delavirdine.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended. (Major) In a study involving 6 HIV-1-infected patients, coadministration of delavirdine 300 mg 3 times daily with clarithromycin 500 mg twice daily resulted in no significant change in delavirdine pharmacokinetics. However, for patients with renal dysfunction, dosage adjustment of clarithromycin is required during concurrent delavirdine treatment due to decreased clarithromycin elimination. The dose of clarithromycin should be reduced by 50% for patients with a creatinine clearance of 30 to 60 ml/min and for patients with a creatinine clearance of < 30 ml/min, the dose of clarithromycin should be reduced by 75%.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended. (Major) In a study involving 6 HIV-1-infected patients, coadministration of delavirdine 300 mg 3 times daily with clarithromycin 500 mg twice daily resulted in no significant change in delavirdine pharmacokinetics. However, for patients with renal dysfunction, dosage adjustment of clarithromycin is required during concurrent delavirdine treatment due to decreased clarithromycin elimination. The dose of clarithromycin should be reduced by 50% for patients with a creatinine clearance of 30 to 60 ml/min and for patients with a creatinine clearance of < 30 ml/min, the dose of clarithromycin should be reduced by 75%.
    Amphetamines: (Moderate) Warn patients that there are potentially serious drug interactions between delavirdine and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as delavirdine. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Amprenavir: (Major) Concurrent administration of delavirdine and amprenavir is not recommended. Coadministration results in decreased serum concentrations of delavirdine and increased serum concentrations of amprenavir.
    Antacids: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Apalutamide: (Major) Coadministration of delavirdine with apalutamide is not recommended as there is a potential for decreased delavirdine concentrations; exposure to apalutamide may also increase. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Delavirdine is a CYP3A4 substrate and strong inhibitor. Apalutamide is a CYP3A4 substrate and strong inducer.
    Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of delavirdine with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased delavirdine exposure may also occur. If coadministration cannot be avoided, use caution and monitor for an increase in delavirdine- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Delavirdine 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. Delavirdine 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 delavirdine. 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.
    Aripiprazole: (Major) Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as delavirdine. Adults receiving a combination of a CYP3A4 and 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as delavirdine, 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. Patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 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 a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Adult patients receiving a combination of a CYP3A4 and 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 a strong CYP3A4 inhibitor 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 a strong CYP3A4 inhibitor 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 strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Artemether; Lumefantrine: (Moderate) Delavirdine is a substrate/inhibitor and artemether is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations. Concomitant use warrants caution due to the potential for increased side effects. (Moderate) Delavirdine is a substrate/inhibitor and lumefantrine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with delavirdine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of delavirdine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Aspirin, ASA; Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as delavirdine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy. (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as delavirdine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Aspirin, ASA; Omeprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of delavirdine is necessary. If delavirdine 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 delavirdine 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 delavirdine 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.
    Atazanavir: (Moderate) Delavirdine and atazanavir are both substrates and inhibitors of CYP3A4. Coadministration may result in increased plasma concentrations of either drug. It is not clear if any dosage adjustments are needed.
    Atazanavir; Cobicistat: (Moderate) Delavirdine and atazanavir are both substrates and inhibitors of CYP3A4. Coadministration may result in increased plasma concentrations of either drug. It is not clear if any dosage adjustments are needed. (Moderate) The plasma concentrations of delavirdine and cobicistat may be elevated when administered concurrently. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP2D6 and CYP3A4 substrate/inhibitor. Cobicistat is a substrate/inhibitor of both CYP2D6 and CYP3A4.
    Atomoxetine: (Major) Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as delavirdine may increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, QT prolongation).
    Atorvastatin: (Major) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Coadminister delavirdine and atorvastatin cautiously; use the lowest possible dose of atorvastatin. Delavirdine is a potent inhibitor of CYP3A4. Atorvastatin is a substrate of CYP3A4. If these drugs are coadministered, carefully monitor the patient. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Atorvastatin; Ezetimibe: (Major) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Coadminister delavirdine and atorvastatin cautiously; use the lowest possible dose of atorvastatin. Delavirdine is a potent inhibitor of CYP3A4. Atorvastatin is a substrate of CYP3A4. If these drugs are coadministered, carefully monitor the patient. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors including delavirdine, should not take avanafil.
    Axitinib: (Major) Avoid coadministration of axitinib with delavirdine due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately 50%; 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 delavirdine is discontinued; inhibition of hepatic CYP3A activity by delavirdine is reversible within 1 week of discontinuation. Axitinib is primarily metabolized by CYP3A4. Delavirdine 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 delavirdine 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; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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.
    Barbiturates: (Major) Barbiturates may increase the metabolism of delavirdine, lead to substantial reductions in delavirdine concentrations and efficacy. The manufacturer recommends that delavirdine not be given with barbiturates when used as anticonvulsants due to the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV. In addition, delavirdine may inhibit the metabolism of the barbiturates. If used concomitantly, the patient should be observed for changes in the clinical efficacy and concentrations of the antiretroviral and anticonvulsant regimens.
    Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as delavirdine, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, delavirdine may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Belladonna; Opium: (Major) Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates alfentanil, fentanyl, hydrocodone, morphine, sufentanil, and oxycodone may be noted. Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and meperidine or propoxyphene is not recommended. Delavirdine may decrease the efficacy of codeine-containing analgesics by inhibiting the conversion of codeine to morphine via CYP2D6. Delavirdine may also inhibit the metabolism of methadone, requiring a decrease in methadone doses.
    Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with delavirdine 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 delavirdine 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 delavirdine 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 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and an in vitro inhibitor of CYP2D6.
    Bepridil: (Severe) The concurrent use of bepridil and anti-retroviral protease inhibitors should be avoided where possible, due to the potential for serious toxicity.Delavirdine may significantly inhibit the metabolism of bepridil.
    Betamethasone: (Moderate) Monitor for corticosteroid-related adverse effects if coadministration is necessary. Consider using an alternative treatment to betametasone, such as a corticosteroid less affected by CYP3A4 (i.e., beclomethasone or prednisolone), particularly if long term use is indicated. Delavirdine 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.
    Bicalutamide: (Major) Caution is advised during coadministration of bicalutamide and delavirdine. Bicalutamide is metabolized by CYP3A4. Potent inhibitors of CYP3A4, such as delaviridine, decrease the metabolism and increase the serum concentrations of bicalutamide. This increase may be clinically relevant as adverse reactions to bicalutamide are related to dose and exposure.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering delavirdine with boceprevir due to an increased potential for delavirdine-related adverse events. If delavirdine 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 delavirdine and boceprevir. Both delavirdine and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
    Bortezomib: (Minor) Agents that inhibit cytochrome P450 3A4, such as delavirdine, may increase the exposure to bortezomib and increase the risk for toxicity.
    Bosentan: (Major) Bosentan is a significant inducer of CYP3A4 hepatic enzymes. Theoretically, bosentan may increase the clearance of delavirdine (CYP3A4 substrate); however, this interaction has not been studied. In addition, delavirdine may inhibit two pathways for bosentan metabolism (CYP3A4 and CYP2C9). It is important to review all the medications taken concurrently with bosentan. According to the manufacturer, coadministration of bosentan with a potent CYP2C9 inhibitor plus a CYP3A4 inhibitor is not recommended; large increases in bosentan plasma concentrations are expected with such combinations.
    Brentuximab vedotin: (Minor) Concomitant administration of brentuximab vedotin and delavirdine 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 delavirdine, may alter MMAE exposure as MMAE is a CYP3A4 substrate. Monitor patients for adverse reactions.
    Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Delavirdine is a potent inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a strong CYP3A4 inhibitor. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level.
    Brigatinib: (Major) Avoid coadministration of brigatinib with delavirdine 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 delavirdine, resume the brigatinib dose that was tolerated prior to initiation of delavirdine. Brigatinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
    Brimonidine; Timolol: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2D6 and might decrease the hepatic metabolism of timolol. This interaction may be more pronounced in extensive metabolizers. Clinicians should be alert to exaggerated beta-blocker effects if the timolol is given with delavirdine.
    Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with delavirdine 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; delavirdine is a strong inhibitor of CYP3A4.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Budesonide: (Moderate) Avoid coadministration of oral budesonide and delavirdine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
    Budesonide; Formoterol: (Moderate) Avoid coadministration of oral budesonide and delavirdine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
    Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as delavirdine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Bupivacaine: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as delavirdine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Bupivacaine; Lidocaine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as lidocaine, should be expected with concurrent use of delavirdine. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as delavirdine, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
    Buprenorphine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as buprenorphine, should be expected with concurrent use of delavirdine.
    Buprenorphine; Naloxone: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as buprenorphine, should be expected with concurrent use of delavirdine.
    Buspirone: (Moderate) CYP3A4 inhibitors, such as delaviridine, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with delavirdine 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 delavirdine is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
    Cabozantinib: (Major) Avoid coadministration of cabozantinib with delavirdine due to the risk of increased cabozantinib exposure. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 40 mg/day; 40 mg/day to 20 mg/day); for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 100 mg/day or 100 mg/day to 60 mg/day). Resume the cabozantinib dose that was used prior to initiating treatment with delavirdine 2 to 3 days after discontinuation of delavirdine. Cabozantinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased single-dose cabozantinib exposure by 38%.
    Caffeine; Ergotamine: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Calcium Carbonate: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Calcium Carbonate; Risedronate: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Calcium Carbonate; Simethicone: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Cannabidiol: (Moderate) Consider a dose reduction of cannabidiol if coadministered with delavirdine. Coadministration may increase cannabidiol plasma concentrations increasing the risk of adverse reactions. Cannabidiol is metabolized by CYP3A4 and CYP2C19; delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2C19.
    Carbamazepine: (Severe) Coadministration of carbamazepine and delavirdine is contraindicated due to the potential for loss of virologic response and possible resistance to delavirdine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Delavirdine may also increase plasma concentrations of carbamazepine. Delavirdine and carbamazepine are both substrates of CYP3A4; however, carbamazepine is a potent CYP3A4 inducer while delavirdine is a potent CYP3A4 inhibitor.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as delavirdine, 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.
    Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as delavirdine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
    Carvedilol: (Minor) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, including carvedilol.
    Celecoxib: (Minor) Delavirdine inhibits CYP2C9 and may increase concentrations of other drugs metabolized by this enzyme, including celecoxib.
    Ceritinib: (Major) Avoid coadministration of ceritinib with delavirdine due to increased exposure to ceritinib; plasma concentrations of delavirdine may also increase. If concomitant use is unavoidable, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg; monitor for ceritinib-related adverse reactions. After delavirdine is discontinued, resume the dose of ceritinib taken prior to initiating delavirdine. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. Coadministration with another strong CYP3A4 inhibitor increased ceritinib exposure by 2.9-fold after a single dose in healthy subjects.
    Cevimeline: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as cevimeline, should be expected with concurrent use of delavirdine.
    Chlordiazepoxide: (Moderate) Delavirdine is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
    Chlordiazepoxide; Clidinium: (Moderate) Delavirdine is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Chlorpheniramine; Dextromethorphan: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with delavirdine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of delavirdine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with delavirdine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of delavirdine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Cilostazol: (Major) Cilostazol is extensively metabolized by the cytochrome P450 CYP 3A4 hepatic isoenzyme and appears to have pharmacokinetic interactions with many medications that are potent inhibitors of CYP3A4, such as delaviridine.
    Cimetidine: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
    Ciprofloxacin: (Moderate) The plasma concentrations of delavirdine may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP3A4 substrate and ciprofloxacin is an inhibitor of CYP3A4.
    Cisapride: (Severe) Concurrent use of cisapride with delavirdine is contraindicated. Delavirdine is a potent inhibitor of the CYP3A4, and cisapride is metabolized by this enzyme. Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes and death, have been reported when known and potent inhibitors of CYP3A4 are coadministered with cisapride.
    Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with delavirdine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Clarithromycin: (Major) In a study involving 6 HIV-1-infected patients, coadministration of delavirdine 300 mg 3 times daily with clarithromycin 500 mg twice daily resulted in no significant change in delavirdine pharmacokinetics. However, for patients with renal dysfunction, dosage adjustment of clarithromycin is required during concurrent delavirdine treatment due to decreased clarithromycin elimination. The dose of clarithromycin should be reduced by 50% for patients with a creatinine clearance of 30 to 60 ml/min and for patients with a creatinine clearance of < 30 ml/min, the dose of clarithromycin should be reduced by 75%.
    Clindamycin: (Moderate) Concomitant use of clindamycin and delavirdine may decrease clindamycin clearance and increase the risk of adverse reactions. Clindamycin is a CYP3A4 substrate; delavirdine is a strong inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
    Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of delavirdine. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and delavirdine is an inhibitor of CYP2C19 in vitro. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
    Clomipramine: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Clonazepam: (Moderate) Use delavirdine 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. Delavirdine is a CYP3A4 inhibitor.
    Clorazepate: (Moderate) Due to potential inhibition of clorazepate metabolism, it is recommended that clorazepate be avoided or reduced doses given when concurrent therapy includes delavirdine.
    Clozapine: (Moderate) Caution is advisable during concurrent use of delavirdine and clozapine. Delavirdine is an inhibitor of CYP2D6 and CYP3A4, two of the isoenzymes responsible for the metabolism of clozapine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP3A4 or CYP2D6 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Moderate) The plasma concentrations of delavirdine and cobicistat may be elevated when administered concurrently. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP2D6 and CYP3A4 substrate/inhibitor. Cobicistat is a substrate/inhibitor of both CYP2D6 and CYP3A4.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with delavirdine due to the risk of cobimetinib toxicity. Cobimetinib is a CYP3A substrate in vitro, and delavirdine is a strong inhibitor of CYP3A. 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 delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with delavirdine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of delavirdine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and delavirdine 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. Delavirdine can inhibit colchicine's metabolism via 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 a strong CYP3A4 inhibitor like delavirdine 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.
    Colchicine; Probenecid: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and delavirdine 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. Delavirdine can inhibit colchicine's metabolism via 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 a strong CYP3A4 inhibitor like delavirdine 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: (Major) Coadministration of conivaptan, which is extensively metabolized by CYP3A4 isoenzymes, with a potent CYP3A4 inhibitor could lead to increased conivaptan serum concentrations. Due to the contraindications noted by the manufacturer, it is prudent to avoid coadministration of conivaptan with other CYP3A4 inhibitors, including delavirdine.
    Conjugated Estrogens: (Severe) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as delavirdine may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Conjugated Estrogens; Bazedoxifene: (Severe) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as delavirdine may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Conjugated Estrogens; Medroxyprogesterone: (Severe) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as delavirdine may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Copanlisib: (Major) Avoid the concomitant use of copanlisib and delavirdine 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; delavirdine is a strong CYP3A inhibitor.
    Crizotinib: (Major) Avoid coadministration of delavirdine with crizotinib due to increased plasma concentrations of crizotinib. If concomitant use is unavoidable, reduce the dose of crizotinib to 250 mg by mouth once daily; resume the original crizotinib dose after discontinuation of delavirdine. Crizotinib is a CYP3A substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with one strong CYP3A inhibitor increased the AUC and Cmax of single-dose crizotinib by 216% and 44%, respectively. Concomitant use with another strong CYP3A4 inhibitor increased the steady-state AUC and Cmax of crizotinib by 57% and 33%, respectively, compared to crizotinib alone.
    Cyclosporine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as cyclosporine, should be expected with concurrent use of delavirdine.
    Dabrafenib: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and a moderate CYP3A4 inducer, and delavirdine, a strong CYP3A4 inhibitor and a CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of delavirdine efficacy.
    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 delavirdine. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
    Dapagliflozin; Saxagliptin: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as delavirdine. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together.
    Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with delavirdine due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor.
    Darunavir: (Moderate) Delavirdine and darunavir are both substrates and inhibitors of CYP3A4. In addition, darunavir may inhibit the CYP2D6 metabolism of delavirdine. Coadministration may result in increased plasma concentrations of either drug. It is not clear if any dosage adjustments are needed.
    Darunavir; Cobicistat: (Moderate) Delavirdine and darunavir are both substrates and inhibitors of CYP3A4. In addition, darunavir may inhibit the CYP2D6 metabolism of delavirdine. Coadministration may result in increased plasma concentrations of either drug. It is not clear if any dosage adjustments are needed. (Moderate) The plasma concentrations of delavirdine and cobicistat may be elevated when administered concurrently. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP2D6 and CYP3A4 substrate/inhibitor. Cobicistat is a substrate/inhibitor of both CYP2D6 and CYP3A4.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Delavirdine and darunavir are both substrates and inhibitors of CYP3A4. In addition, darunavir may inhibit the CYP2D6 metabolism of delavirdine. Coadministration may result in increased plasma concentrations of either drug. It is not clear if any dosage adjustments are needed. (Moderate) The plasma concentrations of delavirdine and cobicistat may be elevated when administered concurrently. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP2D6 and CYP3A4 substrate/inhibitor. Cobicistat is a substrate/inhibitor of both CYP2D6 and CYP3A4.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of delavirdine with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of delavirdine, dasabuvir, paritaprevir, and ritonavir. During concurrent administration of delavirdine with ritonavir, increased ritonavir AUC (70%) has been noted. Appropriate doses of ritonavir in combination with delavirdine in regard to safety, efficacy, and pharmacokinetics have not been established. Both delavirdine and ritonavir are CYP3A4 potent inhibitors and substrates as well as CYP2D6 inhibitors and substrates. Paritaprevir and dasabuvir (minor) are CYP3A4 substrates. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Concurrent administration of delavirdine with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of delavirdine, dasabuvir, paritaprevir, and ritonavir. During concurrent administration of delavirdine with ritonavir, increased ritonavir AUC (70%) has been noted. Appropriate doses of ritonavir in combination with delavirdine in regard to safety, efficacy, and pharmacokinetics have not been established. Both delavirdine and ritonavir CYP3A4 potent inhibitors and substrates as well as CYP2D6 inhibitors and substrates. Paritaprevir and dasabuvir (minor) are CYP3A4 substrates. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Monitor for increased toxicity of ritonavir during coadministration of delavirdine. Appropriate doses of ritonavir in combination with delavirdine with respect to safety and efficacy have not been established. The exposure to ritonavir has been increased by 70% during concurrent administration of delavirdine.
    Dasatinib: (Major) Avoid coadministration of dasatinib and delavirdine due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to delavirdine 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. Concomitant use of delavirdine is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If delavirdine is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. 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 delavirdine. 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; delavirdine 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.
    Desipramine: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Dexamethasone: (Minor) Since dexamethasone may induce metabolism of delavirdine, concomitant use of these agents should be done with caution. Delavirdine therapy may be less effective due to decreased plasma levels in patients taking these drugs concomitantly.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dexlansoprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Dextromethorphan: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Promethazine: (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Quinidine: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. Increased quinidine concentrations may be associated with severe cardiovascular adverse reactions. Quinidine doses may require adjustment if delavirdine is added or discontinued during quinidine therapy. (Moderate) Delavirdine inhibits CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Diazepam: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as diazepam, should be expected with concurrent use of delavirdine.
    Diclofenac: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as delavirdine; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Diclofenac; Misoprostol: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as delavirdine; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Didanosine, ddI: (Major) The administration of delavirdine concurrently with didanosine, ddI, tablets or oral solution results in a 20% decrease in systemic exposure of both drugs. Didanosine tablets and oral solutions contain buffers that increase gastric pH; therefore, administration of delavirdine and didanosine tablets and oral solution should be separated by at least one hour. Didanosine capsules do not contain buffers and would not be expected to interact with delavirdine.
    Dienogest; Estradiol valerate: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with delavirdine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or 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 adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of delavirdine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If delavirdine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Dihydroergotamine: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Diltiazem: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as diltiazem, should be expected with concurrent use of delavirdine.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Disopyramide: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as disopyramide, should be expected with concurrent use. Coadministration should be approached with caution due to the potential for serious disopyramide toxicity.
    Docetaxel: (Major) Avoid coadministration of docetaxel with delavirdine 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 delavirdine is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Dofetilide: (Severe) Avoid concurrent use of dofetilide with delavirdine. Delavirdine may theoretically inhibit the CYP3A4 metabolism of dofetilide, resulting in elevated dofetilide plasma concentrations. Dofetilide plasma concentrations are correlated with the risk of drug-induced proarrhythmias.
    Dolutegravir; Rilpivirine: (Major) Coadministration of delavirdine and rilpivirine is not recommended. If they are coadministered, close clinical monitoring is advised due to the increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Delavirdine is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
    Donepezil: (Minor) Monitor for increased donepezil effects if coadministered with delavirdine. Delavirdine 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: (Minor) Monitor for increased donepezil effects if coadministered with delavirdine. Delavirdine 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 delavirdine may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; delavirdine 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: (Minor) Coadministration of doravirine and delavirdine may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; delavirdine 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.
    Dorzolamide; Timolol: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2D6 and might decrease the hepatic metabolism of timolol. This interaction may be more pronounced in extensive metabolizers. Clinicians should be alert to exaggerated beta-blocker effects if the timolol is given with delavirdine.
    Doxazosin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with delavirdine. Delavirdine 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.
    Doxepin: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like delavirdine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Doxorubicin: (Major) Delavirdine is a potent CYP3A4 inhibitor as well as a CYP2D6 inhibitor; doxorubicin is a major CYP2D6 and CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of delavirdine and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dronabinol: (Major) Use caution if coadministration of dronabinol with delavirdine is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Delavirdine is a strong inhibitor of CYP3A4 and a moderate CYP2C9 inhibitor in vitro; it is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
    Dronedarone: (Severe) The concomitant use of dronedarone and delavirdine is contraindicated. Coadministration of dronedarone with strong CYP3A4 inhibitors significantly increases dronedarone exposure and the risk of adverse events. Dronedarone is metabolized by CYP3A and is a moderate inhibitor of CYP3A. Delavirdine is a strong inhibitor of CYP3A4 and is a CYP3A substrate. The effects of dronedarone on the pharmacokinetics of delavirdine have not been described, although an increase in delavirdine serum concentrations is possible.
    Drospirenone: (Minor) Delavirdine is a strong CYP3A4 inhibitor. Serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when CYP3A4 inhibitors are coadministered with drospirenone; estradiol. In addition, 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.
    Drospirenone; Estradiol: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives. (Minor) Delavirdine is a strong CYP3A4 inhibitor. Serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when CYP3A4 inhibitors are coadministered with drospirenone; estradiol. In addition, 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.
    Drospirenone; Ethinyl Estradiol: (Minor) Delavirdine is a strong CYP3A4 inhibitor. Serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when CYP3A4 inhibitors are coadministered with drospirenone; estradiol. In addition, 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. (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Delavirdine is a strong CYP3A4 inhibitor. Serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when CYP3A4 inhibitors are coadministered with drospirenone; estradiol. In addition, 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. (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    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 delavirdine 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 delavirdine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as delavirdine, 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 delavirdine 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 when coadministered with delavirdine. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; delavirdine is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as delavirdine.
    Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, one study with etravirine did not show a significant effect of Echinacea on drug exposure. More study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
    Efavirenz: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, efavirenz and delavirdine should not be coadministered.
    Efavirenz; Emtricitabine; Tenofovir: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, efavirenz and delavirdine should not be coadministered.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, efavirenz and delavirdine should not be coadministered.
    Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and delavirdine for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and delavirdine to 6 months. Monitor for elagolix-related side effects and reduced response to delavirdine. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; delavirdine is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease delavirdine concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
    Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with delavirdine should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Delavirdine is a strong inhibitor of the hepatic enzyme CYP3A, while elbasvir is metabolized by CYP3A. (Major) Concurrent administration of grazoprevir with delavirdine should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Delavirdine is a strong inhibitor of the hepatic enzyme CYP3A, while grazoprevir is metabolized by CYP3A. In addition, plasma concentrations of delavirdine (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
    Eletriptan: (Severe) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of delavirdine due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; delavirdine 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 delavirdine 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 delavirdine 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 delavirdine; 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); delavirdine 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 delavirdine; 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 mg should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); delavirdine is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
    Eliglustat: (Severe) Coadministration of delavirdine and eliglustat is contraindicated. Delavirdine is a strong CYP3A inhibitor and in vitro studies have shown that it also reduces CYP2D6 activity; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A and CYP2D6 inhibitors is expected to increase plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of delavirdine and cobicistat may be elevated when administered concurrently. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP2D6 and CYP3A4 substrate/inhibitor. Cobicistat is a substrate/inhibitor of both CYP2D6 and CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of delavirdine and cobicistat may be elevated when administered concurrently. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP2D6 and CYP3A4 substrate/inhibitor. Cobicistat is a substrate/inhibitor of both CYP2D6 and CYP3A4.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Coadministration of delavirdine and rilpivirine is not recommended. If they are coadministered, close clinical monitoring is advised due to the increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Delavirdine is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Coadministration of delavirdine and rilpivirine is not recommended. If they are coadministered, close clinical monitoring is advised due to the increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Delavirdine is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
    Enalapril; Felodipine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as felodipine, should be expected with concurrent use of delavirdine.
    Encainide: (Severe) Encainide is primarily metabolized by CYP2D6, and delavirdine is a CYP2D6 inhibitor. Since encainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions, caution is recommended during concurrent use. Monitor clinical response and adjust encainide dosage if necessary.
    Encorafenib: (Major) Avoid coadministration of encorafenib and delavirdine due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of delavirdine. If delavirdine is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of delavirdine. Encorafenib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. 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.
    Entrectinib: (Major) Avoid coadministration of entrectinib with delavirdine due to 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 delavirdine is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of delavirdine. Entrectinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
    Enzalutamide: (Major) Coadministration of delavirdine with enzalutamide is not recommended as there is a potential for decreased delavirdine concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Delavirdine is metabolized by CYP3A4 and enzalutamide is a strong CYP3A4 inducer.
    Eplerenone: (Severe) Coadministration of delavirdine and eplerenone is contraindicated. Delavirdine 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 delavirdine 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 delavirdine is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and delavirdine 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: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Ergonovine: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Ergot alkaloids: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Ergotamine: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Erlotinib: (Major) Avoid coadministration of erlotinib with delavirdine 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 delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
    Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with delavirdine, a CYP2C19 and potent CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
    Esomeprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Esomeprazole; Naproxen: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Estazolam: (Moderate) Delavirdine is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity.
    Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as delavirdine may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Esterified Estrogens; Methyltestosterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as delavirdine may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Estradiol: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Estradiol; Levonorgestrel: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Estradiol; Norethindrone: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Estradiol; Norgestimate: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Estradiol; Progesterone: (Minor) As delavirdine inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
    Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as delavirdine may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Eszopiclone: (Major) The adult dose of eszopiclone should not exceed 2 mg/day during co-administration of potent CYP3A4 inhibitors, such as delavirdine. 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: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Desogestrel: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Etonogestrel: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Levonorgestrel: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norelgestromin: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norethindrone: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norgestimate: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethinyl Estradiol; Norgestrel: (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Ethosuximide: (Moderate) Delavirdine may inhibit the metabolism of ethosuximide and may necessitate up to a 50% dose reduction of ethosuximide.
    Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with delavirdine. Delavirdine is a strong inhibitor of CYP3A4 and etoposide, VP-16 is a CYP3A4 substrate. Coadministration may increase etoposide concentrations.
    Etravirine: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, etravirine and delavirdine should not be coadministered.
    Everolimus: (Major) Avoid coadministration of delavirdine with everolimus (Afinitor; Afinitor Disperz) due to increased plasma concentrations of everolimus. Coadministration of delavirdine with everolimus (Zortress) is not recommended without close monitoring of everolimus whole blood trough concentrations. Everolimus is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor.
    Ezetimibe; Simvastatin: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate simvastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Famotidine: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
    Famotidine; Ibuprofen: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
    Fedratinib: (Major) Avoid coadministration of fedratinib with delavirdine as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If delavirdine 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; delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
    Felodipine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as felodipine, should be expected with concurrent use of delavirdine.
    Fentanyl: (Major) Delavirdine is a potent inhibitor of CYP3A4. Increased concentrations of the CYP3A4 substrate fentanyl are expected with coadministration. Fentanyl should be used with extreme caution if deemed appropriate for use in a patient taking delavirdine. The fentanyl dose may need to be very conservative, and the patient should be carefully monitored for an extended time period for signs of too much fentanyl such as oversedation, respiratory depression, and hypotension.
    Fesoterodine: (Moderate) Fesoterodineis rapidly hydrolyzed to its active metabolite, 5-hydroxymethyltolterodine, which is metabolized via hepatic CYP3A4 and 2D6. In theory, the CYP3A4 and 2D6 inhibitory effects of delavirdine may result in an increase in plasma concentrations of 5-hydroxymethyltolterodine. Fesoterodine doses greater than 4 mg/day are not recommended during concurrent use of potent 3A4 inhibitors.
    Flecainide: (Severe) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as flecainide. Caution is recommended when administering these drugs together, as flecainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
    Flibanserin: (Severe) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as delavirdine, 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.
    Fluoxetine: (Minor) Delavirdine is metabolized by CYP2D6 and CYP3A4. Fluoxetine impairs both of these pathways at therapeutic doses. This interaction can result in substantial increases in the trough levels of delavirdine, up to a 50% increase.
    Fluoxetine; Olanzapine: (Minor) Delavirdine is metabolized by CYP2D6 and CYP3A4. Fluoxetine impairs both of these pathways at therapeutic doses. This interaction can result in substantial increases in the trough levels of delavirdine, up to a 50% increase.
    Flurazepam: (Moderate) Due to potential inhibition of flurazepam metabolism, it is recommended that flurazepam be avoided or reduced doses given when concurrent therapy includes delavirdine.
    Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and delavirdine 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; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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 delavirdine 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; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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; Umeclidinium; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and delavirdine 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; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and delavirdine 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; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone 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.
    Fluvastatin: (Moderate) Concurrent use of delavirdine with fluvastatin should be done cautiously. Coadministration of fluvastatin with delavirdine may increase the risk of myopathy and rhabdomyolysis. Delavirdine inhibits CYP2C9, which is the isoenzyme primarily responsible for the metabolism of fluvastatin.
    Food: (Moderate) The pharmacokinetic parameters of anti-retroviral medications (anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs), anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs), anti-retroviral nucleotide reverse transcriptase inhibitors, and anti-retroviral protease inhibitors) metabolized through the CYP isoenzyme system are slightly altered by smoked and oral marijuana. Despite this interaction, marijuana is not expected to adversely affect anti-retroviral efficacy. However, the incidence of marijuana associated adverse effects may change following coadministration with anti-retroviral drugs. Many anti-retrovirals are inhibitors 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 anti-retrovirals, 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; Mometasone: (Moderate) Concomitant administration of delavirdine and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with delavirdine long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor.
    Fosamprenavir: (Severe) The coadministration of fosamprenavir with delavirdine is contraindicated. Coadministration may lead to loss of virologic response and possible resistance to delavirdine. In addition, the coadministration of delavirdine and fosamprenavir results in increased serum concentrations of fosamprenavir's active metabolite, amprenavir.
    Fosphenytoin: (Severe) Concurrent use of fosphenytoin and delavirdine is contraindicated due to the potential for subtherapeutic antiretroviral activity and development of resistant mutations of HIV. In addition, delavirdine may inhibit the CYP metabolism of fosphenytoin, resulting in increased phenytoin concentrations and possible side effects.
    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; delavirdine is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
    Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with delavirdine is necessary; the risk is increased in CYP2D6 poor metabolizers. Gefitinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%. Based on in vitro data, gefitinib is also metabolized to O-desmethyl gefitinib by CYP2D6 and delavirdine is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends additional precautions based on exposure in patients with poor CYP2D6 metabolism.
    Gilteritinib: (Major) Consider an alternative to delavirdine during treatment with gilteritinib. Concurrent use may increase gilteritinib exposure resulting in treatment-related adverse events. If coadministration is required, frequently monitor for gilteritinib adverse reactions. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study.
    Glasdegib: (Major) Consider an alternative to delavirdine during treatment with glasdegib. Concurrent use may increase glasdegib exposure resulting in treatment-related adverse events including QT prolongation. If coadministration cannot be avoided, monitor for increased adverse events; more frequent ECG monitoring is recommended. Glasdegib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Guanfacine: (Major) Delavirdine 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 delavirdine is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and delavirdine is a strong CYP3A4 inhibitor.
    H2-blockers: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
    Halofantrine: (Moderate) Drugs which significantly inhibit cytochrome CYP3A4, such as delavirdine, may lead to an inhibition of halofantrine metabolism, placing the patient at risk for halofantrine cardiac toxicity. If concurrent use of halofantrine and a CYP3A4 inhibitor is warranted, it would be prudent to use caution and monitor the ECG periodically
    Haloperidol: (Moderate) Delavirdine is an inhibitor of CYP2D6. Coadministration may result in decreased haloperidol metabolism and increased toxicity with concurrent use. Neurologic side effects have been noted clinically in some patients as a result of impaired haloperidol elimination.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydrochlorothiazide, HCTZ; Losartan: (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as delavirdine, have potential to inhibit the conversion of losartan to its active metabolite E-3174. The importance of theoretical CYP2C9 interactions has not been established; monitor therapeutic response to individualize losartan dosage.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Propranolol is significantly metabolized by CYP2D6 isoenzymes and CYP2D6 inhibitors, such as delavirdine, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with delavirdine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of delavirdine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If delavirdine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Delavirdine is a strong inhibitor of CYP3A4 and a moderate inhibitor of CYP2D6.
    Hydromorphone: (Major) Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates alfentanil, fentanyl, hydrocodone, morphine, sufentanil, and oxycodone may be noted. Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and meperidine or propoxyphene is not recommended. Delavirdine may decrease the efficacy of codeine-containing analgesics by inhibiting the conversion of codeine to morphine via CYP2D6. Delavirdine may also inhibit the metabolism of methadone, requiring a decrease in methadone doses.
    Ibrutinib: (Severe) Delavirdine is contraindicated for use with medications that are highly dependent on CYP3A4 for clearance and are associated with serious and/or life-threatening events, such as ibrutinib. Significantly increased ibrutinib levels may occur. Ibrutinib is a CYP3A4 substrate; delavirdine is a strong CYP3A 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 delavirdine is necessary. If delavirdine 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 delavirdine 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 delavirdine 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.
    Idelalisib: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and delavirdine, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while delavirdineis 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 delavirdine.
    Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with delavirdine is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Delavirdine is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
    Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with delavirdine. If delavirdine is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Iloperidone is a CYP3A4 substrate. Delavirdine is a strong CYP3A4 inhibitor. 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) Coadministration may result in elevated plasma concentrations of both drugs. Imatinib is a CYP3A4 substrate and moderate CYP3A4 inhibitor. Delavirdine is a CYP3A4 substrate and strong CYP3A4 inhibitor.
    Imipramine: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Indinavir: (Major) Reduce the adult indinavir dose to 600 mg three times daily when coadministered with delavirdine. At this dose, concurrent use results in increased indinavir AUC (53%) and Cmin (298%). Indinavir has no effects on delavirdine pharmacokinetics.
    Interferon Alfa-2a: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Alfa-2b: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Alfa-2b; Ribavirin: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. (Major) The concomitant use of ribavirin and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Alfacon-1: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Alfa-n3: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Beta-1a: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Beta-1b: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Gamma-1b: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Irinotecan Liposomal: (Major) Avoid administration of delavirdine 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 delavirdine is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan.
    Irinotecan: (Major) Avoid administration of delavirdine 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 delavirdine is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan.
    Isavuconazonium: (Severe) Concomitant use of isavuconazonium with delavirdine 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; delavirdine 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 delavirdine concentrations would also be expected with coadministration, as delavirdine is a substrate and isavuconazole is a moderate inhibitor of CYP3A4.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Severe) Rifampin decreases delavirdine concentrations by 97%. Do not administer delavirdine with rifampin because of the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV.
    Isoniazid, INH; Rifampin: (Severe) Rifampin decreases delavirdine concentrations by 97%. Do not administer delavirdine with rifampin because of the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV.
    Isradipine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as isradipine, should be expected with concurrent use of delavirdine.
    Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with delavirdine as istradefylline exposure and adverse effects may increase. Delavirdine 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: (Minor) Trough plasma concentrations of delavirdine may be increased in patients receiving itraconazole concurrently with delavirdine.
    Ivabradine: (Severe) Coadministration of ivabradine and delavirdine is contraindicated. Ivabradine is primarily metabolized by CYP3A4; delavirdine 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 delavirdine 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 delavirdine 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 delavirdine due to increased plasma concentrations of ivosidenib, which increases the risk of 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 delavirdine is discontinued, wait at least 5 half-lives of delavirdine before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. 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 delavirdine should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment is necessary, strongly consider reducing the adult ixabepilone dose to 20 mg/m2 every 3 weeks (clinical data for this dose adjustment is lacking). 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: (Minor) Ketoconazole is a known inhibitor of cytochrome P450 3A4. Trough plasma concentrations of delavirdine may be increased by about 50% in patients receiving ketoconazole concurrently with delavirdine.
    Lacosamide: (Moderate) Use caution during concurrent use of lacosamide and delavirdine, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; delavirdine is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
    Lansoprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Lansoprazole; Naproxen: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like delavirdine, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Lapatinib: (Major) Avoid coadministration of lapatinib with delavirdine due to increased plasma concentrations of lapatinib. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. If delavirdine is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. 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 delavirdine due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If delavirdine is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of delavirdine. Larotrectinib is a CYP3A4 substrate; delavirdine 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 delavirdine with oral lefamulin due to increased lefamulin exposure; delavirdine may be administered with intravenous lefamulin. Lefamulin is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
    Lesinurad: (Moderate) Use lesinurad and delavirdine together with caution; delavirdine may increase the systemic exposure of lesinurad. Delavirdine is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
    Lesinurad; Allopurinol: (Moderate) Use lesinurad and delavirdine together with caution; delavirdine may increase the systemic exposure of lesinurad. Delavirdine is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
    Letermovir: (Moderate) An increase in the plasma concentration of delavirdine may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Delavirdine is primarily metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Levobupivacaine: (Minor) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs metabolized by this enzyme, such as levobupivacaine, should be expected with concurrent use of delavirdine.
    Levomilnacipran: (Major) The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Delavirdine 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.
    Levorphanol: (Major) Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates alfentanil, fentanyl, hydrocodone, morphine, sufentanil, and oxycodone may be noted. Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and meperidine or propoxyphene is not recommended. Delavirdine may decrease the efficacy of codeine-containing analgesics by inhibiting the conversion of codeine to morphine via CYP2D6. Delavirdine may also inhibit the metabolism of methadone, requiring a decrease in methadone doses.
    Lidocaine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as lidocaine, should be expected with concurrent use of delavirdine.
    Loperamide: (Moderate) The plasma concentration of loperamide, a CYP3A4 and CYP2D6 substrate, may be increased when administered concurrently with delavirdine, an inhibitor of CYP3A4 and CYP2D6. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP3A4 and CYP2D6 substrate, may be increased when administered concurrently with delavirdine, an inhibitor of CYP3A4 and CYP2D6. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Lopinavir; Ritonavir: (Moderate) Monitor for increased toxicity of ritonavir during coadministration of delavirdine. Appropriate doses of ritonavir in combination with delavirdine with respect to safety and efficacy have not been established. The exposure to ritonavir has been increased by 70% during concurrent administration of delavirdine.
    Lorlatinib: (Major) Avoid coadministration of lorlatinib with delavirdine due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions of lorlatinib; plasma concentrations of delavirdine may also decrease. If concomitant use is unavoidable, decrease the starting dose of lorlatinib from 100 mg PO once daily to 75 mg PO once daily. In patients who have already had a dose reduction to 75 mg PO once daily due to adverse reactions, reduce the dose of lorlatinib to 50 mg PO once daily. If delavirdine is discontinued, increase the dose of lorlatinib after 3 plasma half-lives of delavirdine to the dose that was used before starting delavirdine. Lorlatinib is a CYP3A4 substrate and a moderate CYP3A4 inducer. Delavirdine is a CYP3A4 substrate and a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of lorlatinib by 42% and 24%, respectively. Concomitant administration of delavirdine with CYP3A4 inducers may decrease plasma concentrations, reducing efficacy and increasing the potential for viral resistance.
    Losartan: (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as delavirdine, have potential to inhibit the conversion of losartan to its active metabolite E-3174. The importance of theoretical CYP2C9 interactions has not been established; monitor therapeutic response to individualize losartan dosage.
    Lovastatin: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate lovastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Lovastatin; Niacin: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate lovastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Lumacaftor; Ivacaftor: (Major) If delavirdine 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 delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of delavirdine; avoid concurrent use if possible. If concomitant use of delavirdine is necessary, monitor antiretroviral efficacy, consider the use of therapeutic drug monitoring, and adjust drug dosages as necessary. Lumacaftor; ivacaftor dosage adjustment is not required when delavirdine is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking delavirdine, 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 delavirdine. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Delavirdine is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of delavirdine and decrease its therapeutic efficacy. Although delavirdine 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 CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of delavirdine; avoid concurrent use if possible. If concomitant use of delavirdine is necessary, monitor antiretroviral efficacy, consider the use of therapeutic drug monitoring, and adjust drug dosages as necessary. Lumacaftor; ivacaftor dosage adjustment is not required when delavirdine is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking delavirdine, 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 delavirdine. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Delavirdine is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of delavirdine and decrease its therapeutic efficacy. Although delavirdine 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 CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
    Lurasidone: (Severe) Concurrent use of lurasidone with strong CYP3A4 inhibitors, such as delavirdine, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Increased lurasidone plasma concentrations are expected when the drug is co-administered with inhibitors of CYP3A4.
    Macitentan: (Major) Avoid concurrent use of macitentan and delavirdine. Delavirdine 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 delavirdine is necessary.
    Maprotiline: (Moderate) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme including maprotiline. A dosage adjustment of maprotiline may be needed when given concurrently with delavirdine.
    Maraviroc: (Major) Coadministration of maraviroc, a CYP3A substrate, with delavirdine, a strong CYP3A4 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 delavirdine (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.
    Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Delavirdine is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
    Meperidine: (Major) Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and meperidine is not recommended. Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates alfentanil, fentanyl, hydrocodone, morphine, sufentanil, and oxycodone may be noted.
    Meperidine; Promethazine: (Major) Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and meperidine is not recommended. Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates alfentanil, fentanyl, hydrocodone, morphine, sufentanil, and oxycodone may be noted.
    Metformin; Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Delavirdine is a potent inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
    Metformin; Saxagliptin: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as delavirdine. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together.
    Methadone: (Major) The concurrent administration of methadone and inhibitors of cytochrome P450 3A4, such as delavirdine, may result in increased concentrations of methadone. Inhibition of methadone metabolism can lead to toxicity including CNS adverse effects and potential for QT prolongation and torsades de pointes when high doses of methadone are used (e.g., 200 mg/day PO in adult patients). A decrease in methadone doses may be required.
    Methylergonovine: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Methysergide: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Mexiletine: (Major) Because mexiletine is metabolized by CYP2D6, delavirdine which is a potent inhibitor of cytochrome P450 2D6, might decrease the metabolism of mexiletine. Clinicians should be aware of the potential for severe adverse reactions.
    Midazolam: (Severe) Concurrent use of delavirdine and midazolam is contraindicated. Delavirdine is a potent inhibitor of the CYP3A4; midazolam is a CYP3A4 substrate. Coadministration may potentiate the clinical effects of midazolam.
    Midostaurin: (Major) Avoid the concomitant use of midostaurin and delavirdine as significantly increased exposure of midostaurin and its active metabolites may occur resulting in increased toxicity. Consider an alternative agent to replace delavirdine. If coadministration cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity (e.g., gastrointestinal toxicity, hematologic toxicity, bleeding, and infection), particularly during the first week of midostaurin therapy for systemic mastocytosis/mast cell leukemia and the first week of each cycle of midostaurin therapy for acute myeloid leukemia. Midostaurin is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. The AUC values of midostaurin and its metabolites CGP62221 and CGP52421 increased by 10.4-fold, 3.5-fold, and 1.2-fold, respectively, when midostaurin was administered with another strong CYP3A4 inhibitor in a drug interaction study. The Cmin (trough) levels of midostaurin and its metabolites CGP62221 and CGP52421 on day 28 increased by 2.1-fold, 1.2-fold, and 1.3-fold, respectively, when midostaurin was administered with another strong CYP3A4 inhibitor compared with day 21 Cmin levels with midostaurin alone in another drug interaction study.
    Mifepristone: (Major) Medications that are potent CYP3A inhibitors, such as delavirdine, are expected to increase plasma mifepristone concentrations. A dose reduction of the current dose of mifepristone may be required when mifepristone is used chronically to treat hormonal conditions, such as Cushing's disease. Adjust to clinical response. Limit the maximum dose of mifepristone to 600 mg/day PO. In a patient already receiving delavirdine, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 600 mg/day if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with delavirdine 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 delavirdine is initiated in a patient already receiving mifepristone 900 mg or 1200 mg, reduce the mifepristone dose to 600 mg/day. Mifepristone inhibits CYP3A4 and may also reduce delavirdine metabolism via CYP3A4. Monitor for delavirdine-related adverse effects. Common side effects of delavirdine may include abdominal pain, headache, nausea, or vomiting. If a rash occurs along with symptoms such as fever, blisters, mouth sores, swelling, and myalgia or arthralgia, discontinue delavirdine immediately. Due to the slow elimination of mifepristone from the body, interactions that occur may be prolonged.
    Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as delavirdine may be increased when administered with mirabegron. Delavirdine has been shown to be a CYP2D6 substrate invitro. Appropriate monitoring and dose adjustment may be necessary.
    Mirtazapine: (Moderate) In vitro studies have identified mirtazapine as a substrate for several CYP450 isoenzymes including 2D6, 1A2, and 3A4. Pharmacokinetic studies with some CYP3A4 inhibitors have shown that elevations in mirtazapine concentrations are possible during co-administration.Therefore, caution is advised during concurrent use of mirtazapine and potent inhibitors of CYP3A4 such as delavirdine.
    Mitotane: (Major) Concomitant use of mitotane with delavirdine should be undertaken with caution due to potential decreased delavirdine concentrations, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mitotane is a strong CYP3A4 inducer and delavirdine is a CYP3A4 substrate. When coadministered with another strong CYP3A4 inducer (rifampin 600 mg daily; n = 16), the delavirdine Cmax decreased by 90% (90% CI, 83% to 94%), the AUC by 97% (90% CI, 95% to 98%), and the Cmin by 100%.
    Mometasone: (Moderate) Concomitant administration of delavirdine and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with delavirdine long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor.
    Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with delavirdine. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor.
    Naloxegol: (Severe) Concomitant use of naloxegol with delavirdine is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as delavirdine, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
    Nebivolol: (Major) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with delavirdine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as delavirdine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Major) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with delavirdine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as delavirdine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nefazodone: (Major) Both nefazodone and delavirdine are inhibitors and substrates of CYP3A4. Elevated plasma concentrations of both medications may occur during concurrent use. It is essential to evaluate for appropriate dosing of both agents to avoid adverse effects.
    Nelfinavir: (Moderate) Coadministration of delavirdine and nelfinavir results in an increase in nelfinavir and a decrease in delavirdine. A decrease in the active metabolite of nelfinavir is also seen, but is more than compensated for by the increased nelfinavir concentration. Appropriate doses of this combination with respect to safety, efficacy, and pharmacokinetics have not been established. If these drugs are coadministered, patients should be monitored for neutropenia.
    Neratinib: (Major) Avoid concomitant use of delavirdine with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 481%; 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 primarily metabolized through CYP3A4 since the plasma concentrations of the primary substrate can increase; the inhibitory effect on CYP3A4 can last for multiple days. Delavirdine is partially metabolized by CYP3A4. In addition, netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor can significantly increase the systemic exposure to netupitant. Delavirdine is a strong CYP3A4 inhibitor. No dosage adjustment is necessary for single dose administration of netupitant; palonosetron.
    Nevirapine: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, nevirapine and delavirdine should not be coadministered.
    Niacin; Simvastatin: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate simvastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Nicardipine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as nicardipine, should be expected with concurrent use of delavirdine.
    Nifedipine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as nifedipine, should be expected with concurrent use of delavirdine.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and delavirdine. If coadministration is required, monitor patients closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in patients with resistant or intolerant Ph+ CML or to 200 mg once daily in patients with newly diagnosed Ph+ CML. If delavirdine 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 delavirdine is a strong inhibitor of CYP3A4.
    Nimodipine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as nimodipine, should be expected with concurrent use of delavirdine.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with delavirdine due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and delavirdine is a CYP3A4 inhibitor.
    Nizatidine: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
    Nortriptyline: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Olaparib: (Major) Avoid coadministration of olaparib with delavirdine and consider alternative agents with less CYP3A4 inhibition due to increased olaparib exposure. If concomitant use is unavoidable, reduce the dose of olaparib tablets to 100 mg twice daily; reduce the dose of olaparib capsules to 150 mg twice daily. Olaparib is a CYP3A4/5 substrate and delavirdine is a strong CYP3A4 inhibitor.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of delavirdine with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of delavirdine, dasabuvir, paritaprevir, and ritonavir. During concurrent administration of delavirdine with ritonavir, increased ritonavir AUC (70%) has been noted. Appropriate doses of ritonavir in combination with delavirdine in regard to safety, efficacy, and pharmacokinetics have not been established. Both delavirdine and ritonavir CYP3A4 potent inhibitors and substrates as well as CYP2D6 inhibitors and substrates. Paritaprevir and dasabuvir (minor) are CYP3A4 substrates. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Monitor for increased toxicity of ritonavir during coadministration of delavirdine. Appropriate doses of ritonavir in combination with delavirdine with respect to safety and efficacy have not been established. The exposure to ritonavir has been increased by 70% during concurrent administration of delavirdine.
    Omeprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Omeprazole; Sodium Bicarbonate: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended. (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Oritavancin: (Major) Delavirdine is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of delavirdine may be reduced if these drugs are administered concurrently.
    Orlistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Ospemifene: (Major) Administration of delavirdine with ospemifene may increase the risk of ospemifene-related adverse reactions Delavirdine is a strong CYP3A4 inhibitor and also an inhibitor of CYP2C9 and of CYP2C19 whereas ospemifene is a CYP3A4, CYP2C9, and CYP2C19 substrate. A moderate CYP3A/strong CYP2C9 inhibitor increased the systemic exposure of ospemifene by 2.7-fold.
    Oxybutynin: (Moderate) Oxybutynin is metabolized by CYP3A4. Serum concentrations of oxybutynin may be increased if coadministered with inhibitors of CYP3A4 including delavirdine. The manufacturer recommends that caution when oxybutynin is co-administered with CYP3A4 inhibitors.
    Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of delavirdine is necessary. If delavirdine 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 delavirdine 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 delavirdine 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.
    Oxymorphone: (Major) Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates, such as oxycodone may be noted. Delavirdine may decrease the efficacy of codeine-containing analgesics by inhibiting the conversion of codeine to morphine via CYP2D6. Delavirdine may also inhibit the metabolism of methadone, requiring a decrease in methadone doses.
    Paclitaxel: (Minor) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as paclitaxel, should be expected with concurrent use of delavirdine.
    Palbociclib: (Major) Avoid coadministration of delavirdine 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 delavirdine is discontinued, increase the palbociclib dose (after 3 to 5 half-lives of delavirdine) to the dose used before initiation of delavirdine. Palbociclib is primarily metabolized by CYP3A4 and delavirdine 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.
    Pantoprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Paricalcitol: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as delaviridine. 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.
    Paroxetine: (Moderate) Delavirdine is a potent inhibitors of cytochrome P450 2D6, and may theoretically decrease paroxetine metabolism leading to increased adverse reactions.
    Pazopanib: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as delavirdine. 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. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 substrate, and delavirdine, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered pazopanib and/or delavirdine concentrations.
    Peginterferon Alfa-2a: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Peginterferon Alfa-2b: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. In addition, monitor for adverse effects associated with increased exposure to delavirdine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while delavirdine is partially metabolized by CYP2D6.
    Peginterferon beta-1a: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Perampanel: (Moderate) The use of perampanel with delavirdine, a non-nucleoside reverse transcriptase inhibitor of CYP3A4, may increase perampanel plasma concentrations. Perampanel is a substrate of CYP3A4. Monitor patients taking potent CYP3A4 inhibitors for increases in adverse effects such as anger, anxiety, irritability, somnolence, dizziness, or nausea. Dose adjustment may be required.
    Pergolide: (Severe) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
    Perindopril; Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as delavirdine, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when delavirdine is coadministered with amlodipine; therapeutic response should be monitored.
    Perphenazine: (Moderate) Delavirdine is a potent inhibitor of cytochrome P4502D6 and might decrease perphenazine metabolism leading to increased adverse reactions.
    Perphenazine; Amitriptyline: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine. (Moderate) Delavirdine is a potent inhibitor of cytochrome P4502D6 and might decrease perphenazine metabolism leading to increased adverse reactions.
    Pexidartinib: (Major) Avoid coadministration of pexidartinib with delavirdine as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If delavirdine is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of delavirdine. 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; delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Phentermine; Topiramate: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions.
    Phenytoin: (Severe) Concurrent use of phenytoin and delavirdine is contraindicated due to the potential for subtherapeutic antiretroviral activity and development of resistant mutations of HIV. In addition, delavirdine may inhibit the CYP metabolism of phenytoin, resulting in increased phenytoin concentrations and possible side effects.
    Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as delavirdine. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
    Pimozide: (Severe) Coadministration of pimozide and delavirdine is contraindicated. Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as pimozide, should be expected with concurrent use. Elevated pimozide concentrations can lead to QT prolongation, ventricular arrhythmia, and sudden death.
    Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of delavirdine due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; delavirdine is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
    Ponatinib: (Major) Concomitant use of ponatinib, a CYP3A4 substrate, and delavirdine, a strong CYP3A4 inhibitor, may increase the exposure of ponatinib. If the use of both agents is necessary, reduce the starting ponatinib dose to 30 mg/day.
    Posaconazole: (Moderate) Posaconazole and delavirdine should be coadministered with caution due to an increased potential for delavirdine-related adverse events. Both posaconazole and delavirdine are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of delavirdine. These drugs used in combination may result in elevated delavirdine plasma concentrations, causing an increased risk for delavirdine-related adverse events.
    Propafenone: (Major) Caution is recommended when administering propafenone with delavirdine. Delavirdine is a CYP2D6 inhibitor and propafenone is significantly metabolized by this enzyme. Concurrent use may result in elevated propafenone plasma concentrations. Propafenone exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe cardiovascular adverse reactions.
    Propoxyphene: (Major) Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and propoxyphene is not recommended. Propoxyphene is a substrate and an inhibitor of CYP3A4. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP3A4 inhibitor, such as delavirdine. A reduced dosage of propoxyphene may be needed. Monitor patients for central nervous system (CNS) and respiratory depression.
    Propranolol: (Moderate) Propranolol is significantly metabolized by CYP2D6 isoenzymes and CYP2D6 inhibitors, such as delavirdine, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
    Proton pump inhibitors: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Protriptyline: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Quazepam: (Moderate) CYP3A4 inhibitors, such as delavirdine, may reduce the metabolism of quazepam and increase the potential for benzodiazepine toxicity.
    Quetiapine: (Major) If coadministration is required, reduce the quetiapine dose to one sixth of the current dose and monitor for adverse events. Delavirdine is expected to significantly increase exposure to quetiapine. Delavirdine is a potent CYP3A4 inhibitor and quetiapine is a CYP3A4 substrate. If delavirdine is discontinued, increase the quetiapine dose by 6-fold.
    Quinidine: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. Increased quinidine concentrations may be associated with severe cardiovascular adverse reactions. Quinidine doses may require adjustment if delavirdine is added or discontinued during quinidine therapy.
    Rabeprazole: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Ramelteon: (Moderate) Coadministration of ramelteon with inhibitors of CYP3A4, such as delavirdine, may lead to increases in the serum concentrations of ramelteon.
    Ranitidine: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
    Ranolazine: (Severe) Ranolazine is metabolized mainly by CYP3A, and is contraindicated in patients receiving drugs known to be strong CYP3A inhibitors, such as delavirdine. In addition, ranolazine is metabolized to a lesser extent by CYP2D6; delavirdine is a known CYP2D6 inhibitor. Concurrent administration may result in an increase in ranolazine concentrations.
    Red Yeast Rice: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine (a CYP3A4 inhibitor) is given in combination with HMG-CoA reductase inhibitors. Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, coadministration of red yeast rice with delavirdine is not recommended.
    Regorafenib: (Major) Avoid coadministration of regorafenib with delavirdine 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 delavirdine 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.
    Remifentanil: (Major) Delavirdine is a potent inhibitor of CYP3A4 and an inhibitor (in vitro) of CYP2D6, CYP2C9, and CYP2C19. Therefore, delavirdine may alter the response to various opiate agonists. Increased concentrations of the CYP substrates alfentanil, fentanyl, hydrocodone, morphine, sufentanil, and oxycodone may be noted. Due the potential for increased formation of neurotoxic metabolites, concurrent use of delavirdine and meperidine or propoxyphene is not recommended. Delavirdine may decrease the efficacy of codeine-containing analgesics by inhibiting the conversion of codeine to morphine via CYP2D6. Delavirdine may also inhibit the metabolism of methadone, requiring a decrease in methadone doses.
    Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Delavirdine is a potent inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
    Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as delavirdine, 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.
    Ribavirin: (Major) The concomitant use of ribavirin and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Ribociclib: (Severe) Coadministration of ribociclib with delavirdine is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to delavirdine may also increase. Inhibition of hepatic CYP3A activity by delavirdine is reversible within 1 week after discontinuation. Ribociclib is extensively metabolized by CYP3A4 and delavirdine is a strong CYP3A4 inhibitor; exposure to ribociclib may be increased. Additionally, ribociclib is a strong CYP3A4 inhibitor and delavirdine is a CYP3A4 substrate.
    Ribociclib; Letrozole: (Severe) Coadministration of ribociclib with delavirdine is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to delavirdine may also increase. Inhibition of hepatic CYP3A activity by delavirdine is reversible within 1 week after discontinuation. Ribociclib is extensively metabolized by CYP3A4 and delavirdine is a strong CYP3A4 inhibitor; exposure to ribociclib may be increased. Additionally, ribociclib is a strong CYP3A4 inhibitor and delavirdine is a CYP3A4 substrate.
    Rifabutin: (Severe) The coadministration of rifabutin and delavirdine is contraindicated. Concurrent administration results in a 230% increase in rifabutin AUC. However, rifabutin significantly decreases delavirdine plasma concentrations. Clinical pharmacokinetic studies have shown an 82% reduction in delavirdine AUC when rifabutin was given concurrently.
    Rifampin: (Severe) Rifampin decreases delavirdine concentrations by 97%. Do not administer delavirdine with rifampin because of the potential for subtherapeutic antiretroviral activity and the subsequent possibility for the development of resistant mutations of HIV.
    Rifapentine: (Severe) Rifapentine should not be used in combination with delavirdine. HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended. Additionally, rifapentine is an inducer of CYP3A4 and should not be coadministered with delavirdine as this may result in decreased delavirdine plasma concentrations.
    Rilpivirine: (Major) Coadministration of delavirdine and rilpivirine is not recommended. If they are coadministered, close clinical monitoring is advised due to the increased potential for rilpivirine-related adverse events. Predictions about the interaction can be made based on metabolic pathways. Delavirdine is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
    Riociguat: (Moderate) Concomitant use of riociguat with strong cytochrome CYP3A inhibitors may result in hypotension. Delavirdine is a potent inhibitor of CYP3A4. Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP inhibitors. A dose reduction should be considered in patients who may not tolerate the hypotensive effect of riociguat.
    Ritonavir: (Moderate) Monitor for increased toxicity of ritonavir during coadministration of delavirdine. Appropriate doses of ritonavir in combination with delavirdine with respect to safety and efficacy have not been established. The exposure to ritonavir has been increased by 70% during concurrent administration of delavirdine.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and delavirdine may result in increases in rivaroxaban exposure and may increase bleeding risk. Delavirdine is a potent inhibitor of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
    Roflumilast: (Major) Coadminister delavirdine and roflumilast cautiously as this may lead to increased systemic exposure to roflumilast; roflumilast-induced adverse effects may occur. Delavirdine is a strong CYP3A4 inhibitor and roflumilast is a CYP3A4 substrate. In pharmacokinetic study, administration of a single dose of roflumilast in patients receiving one of several CYP3A4 inhibitors resulted in variably increased roflumilast Cmax and AUC, as well as decreased Cmax and increased AUC of the active metabolite roflumilast N-oxide.
    Rolapitant: (Major) Use caution if delavirdine and rolapitant are used concurrently, and monitor for delavirdine-related adverse effects. Delavirdine is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
    Romidepsin: (Moderate) The concomitant use of romidepsin, a CYP3A4 substrate, and delavirdine, a strong CYP3A4 inhibitor, may increase romidepsin plasma exposure. If these agents are used together, monitor patients for signs and symptoms of romidepsin toxicity including hematologic toxicity, infection, and electrocardiogram changes; therapy interruption or discontinuation or a dosage reduction may be required if toxicity develops.
    Ruxolitinib: (Major) Reduce the ruxolitinib dosage during coadministration with delavirdine in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of delavirdine in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor.
    Saquinavir: (Major) Appropriate dosing recommendations for concomitant administration of delavirdine and saquinavir boosted with ritonavir have not been established; thus, use of these drugs together is not recommended. If this combination is prescribed, frequent monitoring of hepatic enzymes should be performed; in a small, preliminary study, elevated hepatic enzymes occurred in 13% of subjects during the first several weeks of using delavirdine and saquinavir in combination. Both delavirdine and saquinavir HGC (Invirase) boosted with ritonavir are inhibitors of CYP3A4; coadministration of delavirdine and saquinavir HGC results in increased saquinavir plasma concentration. The effect on delavirdine pharmacokinetic parameters is not well established. There are insufficient data to support any dosing recommendations for the combination of delavirdine and saquinavir HGC boosted with ritonavir. Delavirdine (400 mg three times daily) in combination with saquinavir (soft gelatin capsules, SGC) (1000 mg three times daily) increased mean saquinavir Cmax (98%), AUC (121%), and Cmin (199%), relative to saquinavir-SGC (1200 mg three times daily) alone. There are limited safety and efficacy data available regarding the use of this combination, although, if coadministered, the dose of saquinavir-SGC should be decreased to 800 mg three times daily.
    Saxagliptin: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as delavirdine. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone and strong CYP3A4 inhibitors such as delaviridine may increase the serum concentration of segesterone. (Minor) The concentration of ethinyl estradiol may increase during concurrent administration of delavirdine. However, the clinical significance of this interaction is unknown.
    Sertraline: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2D6 and 3A4 and might decrease sertraline metabolism leading to increased adverse reactions.
    Sibutramine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as sibutramine, should be expected with concurrent use of delavirdine.
    Sildenafil: (Major) Coadministration of delavirdine is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Delavirdine is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
    Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as delavirdine may cause significant increases in silodosin plasma concentrations.
    Simeprevir: (Major) Avoid concurrent use of simeprevir and delavirdine. Inhibition of CYP3A4 by delavirdine may increase the plasma concentrations of simeprevir, resulting in adverse effects.
    Simvastatin: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate simvastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Simvastatin; Sitagliptin: (Severe) The risk of myopathy, including rhabdomyolysis, may be increased when delavirdine is given in combination with HMG-CoA reductase inhibitors. Concomitant use of delavirdine and the CYP3A4 substrate simvastatin is not recommended. If treatment with an HMG-CoA reductase inhibitor is necessary, pravastatin should also be considered, since it is not significantly metabolized by CYP3A4 or CYP2C9 isoenzymes.
    Siponimod: (Major) Concomitant use of siponimod and delavirdine is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; delavirdine is a moderate CYP2C9/strong CYP3A4 dual inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
    Sirolimus: (Major) Avoid the use of sirolimus with potent CYP3A4 inhibitors, such as delavirdine. Delavirdine may affect absorption and elimination of sirolimus leading to increased blood concentrations. Sirolimus is extensively metabolized by CYP3A4 in the gut and liver and undergoes counter-transport from enterocytes of the small intestine into the gut lumen by the P-glycoprotein drug efflux pump. Sirolimus is potentially recycled between enterocytes and the gut lumen to allow continued metabolism by CYP3A4.
    Sodium Bicarbonate: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with delavirdine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Delavirdine is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with delavirdine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Delavirdine is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
    Solifenacin: (Moderate) Use caution and reduce the solifenacin dose to 5 mg per day when used concomitantly with delavirdine. Solifenacin is significantly metabolized via the CYP3A4 pathway; delavirdine is a strong CYP3A4 inhibitor. Pharmacokinetic studies of the use of solifenacin concomitantly with all CYP3A4 inhibitors have not been performed. The interaction between solifenacin and ketoconazole has been studied. Following the administration of solifenacin 10 mg and ketoconazole 400 mg PO, the peak concentration and AUC increased 150% and 270%, respectively.
    Somatropin, rh-GH: (Minor) When somatropin, an inducer of CYP3A4, and anti-retroviral non-nucleoside reverse transcriptase inhibitors, a CYP3A4 substrate, are coadminsitered, patients should be monitored for changes in anti-retroviral efficacy. Published data indicate HIV-infected patients receiving somatropin for wasting or HIV-associated adipose redistribution syndrome (HARS), did not have decreased antiretroviral effectiveness, as indicated by no change in the concentration of circulating CD4 counts or viral load.
    Sonidegib: (Major) Avoid concomitant use of sonidegib and delavirdine as increased sonidegib plasma are expected, resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Delavirdine is a strong CYP3A4 inhibitor and may significantly increase the level of the CYP3A4 substrate, sonidegib. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
    St. John's Wort, Hypericum perforatum: (Severe) St. John's wort appears to be an inducer of hepatic cytochrome P450 enzymes, particularly CYP3A4 and, it is expected that St. John's wort may significantly decrease the plasma concentrations of delavirdine. Such reductions in plasma concentrations of delavirdine could lead to HIV treatment failures or the development of viral-resistance. St. John's wort in all forms, including teas, should be avoided in HIV patients treated with delavirdine.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if delavirdine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of delavirdine is necessary. If delavirdine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like delavirdine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If delavirdine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
    Sunitinib: (Major) Avoid coadministration of delavirdine with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, consider reducing the dose of sunitinib in 12.5 mg decrements based on individual safety and tolerability to a minimum of 37.5 mg (GIST and RCC) or 25 mg (pNET) daily. In the adjuvant RCC study, the minimum dose administered was 37.5 mg. Sunitinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Suvorexant: (Major) Coadministration of suvorexant and delavirdine is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Tacrolimus: (Major) Tacrolimus is metabolized via the hepatic cytochrome P-450 CYP3A4. Drugs that inhibit this isoenzyme, such as delavirdine, can decrease the metabolism of tacrolimus. Subsequent increased whole blood concentrations of tacrolimus may lead to nephrotoxicity or other side effects. Monitor tacrolimus concentrations carefully if these drugs are coadministered.
    Tadalafil: (Major) Particular caution should be used when prescribing phosphodiesterase type 5 (PDE5) inhibitors to patients receiving delavirdine. Coadministration of delavirdine with these drugs is expected to substantially increase their plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. The manufacturer of tadalafil recommends that in patients receiving concomitant potent CYP3A4 inhibitors, the 'as needed' dose for erectile dysfunction should not exceed 10 mg within a 72 hour time period, and the 'once-daily' dose for erectile dysfunction or benign prostatic hyperplasia should not exceed 2.5 mg. It should be noted that during once daily administration of tadalafil, the presence of continuous plasma tadalafil concentrations may change the potential for interactions with potent inhibitors of CYP3A4. When used for pulmonary arterial hypertension, tadalafil should not be co-administered with potent CYP3A inhibitors.
    Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of delavirdine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as delavirdine, should be avoided.
    Tasimelteon: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as delavirdine, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering delavirdine with telaprevir due to an increased potential for delavirdine-related adverse events. If delavirdine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of delavirdine and telaprevir. Both delavirdine and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
    Telithromycin: (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.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and delavirdine is necessary, as the systemic exposure of delavirdine may be decreased resulting in reduced efficacy and decreased virologic response. If these drugs are used together, monitor patients for suboptimal efficacy of delavirdine; consider increasing the dose of delavirdine if necessary. Delavirdine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temsirolimus: (Major) Avoid coadministration of delavirdine with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of delavirdine before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively.
    Terbinafine: (Moderate) Caution is advised when administering terbinafine with delavirdine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; delavirdine is a substrate of CYP2D6 and an inhibitor of CYP2C9, CYP2C19, and CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered.
    Tezacaftor; Ivacaftor: (Major) If delavirdine 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 delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with delavirdine; 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 mg should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); delavirdine is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
    Thioridazine: (Moderate) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, including thioridazine.
    Thiotepa: (Major) Avoid the concomitant use of thiotepa and delavirdine if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; delavirdine is a strong CYP3A4 inhibitor.
    Ticagrelor: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as delavirdine. Although not studied, ticagrelor is a substrate of CYP3A4/5 and concomitant use with delavirdine may increase ticagrelor exposure which may increase the bleeding risk.
    Timolol: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2D6 and might decrease the hepatic metabolism of timolol. This interaction may be more pronounced in extensive metabolizers. Clinicians should be alert to exaggerated beta-blocker effects if the timolol is given with delavirdine.
    Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with delavirdine. In patients receiving 5 mg twice daily, reduce to 5 mg once daily; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 11 mg once daily of the extended-release formulation, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib exposure is increased when coadministered with delavirdine. Delavirdine is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold.
    Tolbutamide: (Major) Delavirdine is a potent inhibitor of CYP2C9 and may increase concentrations of drugs metabolized by this enzyme, like tolbutamide. Coadministration may lead to hypoglycemia; monitor blood glucose concentration during concurrent treatment.
    Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily if coadministered with delavirdine. Concurrent use may increase tolterodine exposure. Delavirdine is a strong CYP3A4 inhibitor. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers.
    Tolvaptan: (Severe) The concomitant use of tolvaptan and delavirdine is contraindicated. Concurrent use is expected to increase tolvaptan exposure. Tolvaptan is a sensitive CYP3A4 substrate; delavirdine is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
    Topiramate: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions.
    Toremifene: (Major) Avoid coadministration of delavirdine with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner, and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%.
    Trabectedin: (Major) Avoid the concomitant use of trabectedin with delavirdine due to significantly increased trabectedin exposure. If short-term delavirdine (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with ketoconazole (200 mg twice daily for 7.5 days), another strong CYP3A inhibitor, increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% and the Cmax by 22% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
    Tramadol: (Moderate) Since tramadol is primarily metabolized by cytochrome P450 isoenzyme CYP2D6, agents that inhibit this enzyme, such as delavirdine, decrease the metabolism of tramadol. Concomitant use of these agents and tramadol may increase plasma levels of tramadol and decrease concentration of the active metabolite leading to decreased analgesic effects and possibly increased side effects due to higher tramadol concentrations.
    Trandolapril; Verapamil: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as verapamil, should be expected with concurrent use of delavirdine.
    Trazodone: (Major) Avoid coadministration of trazodone with delavirdine due to the potential for increased trazodone exposure and associated adverse effects including QT prolongation. If concurrent use cannot be avoided, consider a reduced dose of trazodone based on tolerability. Trazodone is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone alone.
    Triamcinolone: (Moderate) Delaviridine may inhibit the CYP3A4 metabolism of triamcinolone, resulting in increased plasma triamcinolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving another strong CYP3A4 inhibitor with triamcinolone, resulting in systemic corticosteroid effects including, but not limited to, Cushing syndrome and adrenal suppression. Consider the benefit-risk of concomitant use and monitor for systemic corticosteroid side effects. Consider using an alternative treatment to triamcinolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). In some patients, a corticosteroid dose adjustment may be needed. If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
    Triazolam: (Severe) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as delavirdine, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects.
    Tricyclic antidepressants: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Trimetrexate: (Minor) Delavirdine inhibits the cytochrome P450 CYP3A4 isoenzyme. Concurrent administration of trimetrexate with delavirdine may result in increased trimetrexate levels. Closely monitor patients who receive trimetrexate in combination with delavirdine.
    Trimipramine: (Major) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as tricyclic antidepressants (TCAs). Monitor the patient for side effects associated with TCAs such as an increase in constipation, urinary difficulty, dizziness, or rarely, fast, irregular heartbeat. A dosage adjustment may be needed for TCAs when given concurrently with delavirdine.
    Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and delavirdine is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Upadacitinib: (Moderate) Use upadacitinib with caution in patients receiving chronic treatment with delaviridine as upadacitinib exposure and adverse effects may be increased. Upadacitinib is a CYP3A4 substrate; delaviridine is a strong CYP3A4 inhibitor. Concurrent use of upadacitinib with a strong inhibitor increased upadacitinib exposure by 75%.
    Valbenazine: (Major) The dose of valbenazine should be reduced to 40 mg once daily during co-administration with a strong CYP3A4 inhibitor, such as delavirdine. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, valbenazine concentrations may be higher in patients taking a strong CYP3A4 inhibitor and QT prolongation may become clinically significant.
    Vardenafil: (Major) If used together, the vardenafil tablet dose should not exceed 2.5 mg in a 24-hour period; advise patients to promptly report adverse events such as dizziness, faintness on standing, or prolonged erection. Vardenafil orally disintegrating tablets (ODT) provide increased exposure as compared to the regular tablets; therefore, use with potent CYP3A4 inhibitors such as delavirdine is not recommended. Delavirdine is expected to substantially increase vardenafil plasma concentrations and may result in vardenafil-related adverse events including hypotension, visual changes, and priapism.
    Vemurafenib: (Major) Concomitant use of vemurafenib and delavirdine may result in altered concentrations of delavirdine and increased concentrations vemurafenib. Vemurafenib is a substrate/inducer of CYP3A4 and a weak inhibitor of CYP2D6. Delavirdine is a substrate/inhibitor of CYP3A4 and substrate of CYP2D6. Avoid using these agents together if possible.
    Venetoclax: (Major) Coadministration of delavirdine with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of delavirdine. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 100 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 100 mg/day starting on day 4. Venetoclax is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of strong CYP3A4 inhibitors increased the venetoclax AUC by 90% to 690% in drug interaction studies.
    Venlafaxine: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2D6 and might decrease venlafaxine metabolism leading to increased adverse reactions.
    Verapamil: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as verapamil, should be expected with concurrent use of delavirdine.
    Vilazodone: (Major) Because CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone, the manufacturer of vilazodone recommends that the daily dose not exceed 20 mg/day during concurrent use of a strong CYP3A4 inhibitor, such as delavirdine. The original vilazodone dose can be resumed when the CYP3A4 inhibitor is discontinued.
    Vinblastine: (Moderate) Use vinblastine and delavirdine together with caution; concomitant use may result in increased vinblastine plasma concentrations and increased vinblastine toxicity. Delavirdine is a strong CYP3A4 inhibitor that may increase the plasma concentration of vinblastine, a CYP3A4 substrate.
    Vincristine Liposomal: (Major) Delavirdine is a potent inhibitor of CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vincristine: (Major) Delavirdine is a potent inhibitor of CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with delavirdine is necessary. Vinorelbine is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor.
    Vorapaxar: (Major) Avoid coadministration of vorapaxar and delavirdine. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with delavirdine, a strong CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
    Voriconazole: (Moderate) Concurrent administration of delavirdine and voriconazole may theoretically result in increased voriconazole levels. Careful monitoring of therapeutic and adverse effects of voriconazole is recommended when these drugs are given concurrently.
    Voxelotor: (Major) Avoid coadministration of voxelotor and delavirdine as concurrent use may increase voxelotor exposure and lead to increased toxicity. If coadministration is unavoidable, reduce voxelotor dosage to 1,000 mg PO once daily. Voxelotor is a substrate of CYP3A4; delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase voxelotor exposure by 42% to 83%.
    Warfarin: (Moderate) Delavirdine inhibits CYP2C9 and may increase concentrations of warfarin, which is metabolized by this enzyme. Caution is recommended when administering delavirdine with warfarin.
    Zaleplon: (Moderate) Zaleplon is partially metabolized by CYP3A4, and concurrent use of strong CYP3A4 inhibitors, such as delavirdine, may decrease the clearance of zaleplon. Routine dosage adjustments of zaleplon are not required. Dosage adjustments should be made on an individual basis according to efficacy and tolerability.
    Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with delavirdine. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of delavirdine, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
    Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with delavirdine is necessary. Zolpidem is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with strong CYP3A4 inhibitors increased the AUC of zolpidem by 34% to 70%.

    PREGNANCY AND LACTATION

    Pregnancy

    Antiretroviral prophylaxis should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Delavirdine is classified as FDA pregnancy risk category C. In clinical trials and during the post-marketing period of delavirdine, nine unplanned pregnancies occurred with ten infants born (one set of twins). Of these ten infants, eight were born healthy, one was born HIV-positive but without congenital abnormalities, and one was born prematurely with a small muscular ventricular septal defect to a patient who received approximately 6-weeks of treatment with delavirdine and zidovudine early in the course of pregnancy. Studies in rodents indicate there is the potential for teratogenicity and developmental toxicity. Given the minimal human data, along with the concerns regarding teratogenicity, delavirdine is not recommended for use during pregnancy unless no other alternatives are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; if there is detectable viremia, perform resistance testing. For women not currently receiving antiretroviral therapy when the pregnancy is recognized, determination of treatment should be based on the same parameters used for non-pregnant patients (including resistance testing prior to treatment). Initiate treatment as soon as possible in women who require immediate treatment for their own health. Consideration can be given to delaying therapy after the 1st trimester in mothers receiving therapy solely for the prevention of perinatal transmission; however, earlier initiation of therapy may be more effective in reducing in utero transmission. For women not currently receiving treatment, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing prior to initiating therapy. Zidovudine should be included in the antenatal treatment regimen unless there is severe toxicity associated with use or documented resistance. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit and at least every 3 months; monitor plasma HIV RNA at the initial visit, 2 to 6 weeks after initiating/changing therapy, monthly until undetectable, and then at least every 2 months, and at 34 to 36 weeks gestation. Perform antiretroviral resistance testing in the presence of persistently detectable HIV RNA despite antiretroviral receipt; assess patient adherence and consult an HIV treatment expert to guide changes in therapy. Given the limited data on the effect of combination therapy on the fetus, second trimester ultrasound to assess fetal anatomy may be prudent in women who received antiretroviral therapy during the first trimester (particularly if the regimen included efavirenz). Perform standard glucose screening in women receiving antiretroviral therapy, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. If a woman decides to discontinue therapy, a planned treatment interruption, taking into account the specific pharmacokinetic and administration parameters of each drug, should occur to avoid true or functional monotherapy and the development of resistance. It is strongly recommended that health care providers report cases of antenatal antiretroviral drug exposure to the Antiretroviral Pregnancy Registry; telephone 800—258—4263; fax 800—800—1052; the Antiretroviral Pregnancy Registry is also accessible via the Internet.

    To reduce the risk of postnatal transmission, HIV-infected mothers within the United States are advised by the Centers for Disease Control and Prevention to avoid breast-feeding. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy, including delavirdine. If an HIV-infected mother opts to breast-feed, the infant should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, health care workers may contact the Perinatal HIV Hotline (888-448-8765).[42452] There are limited data regarding the use of delavirdine during breast-feeding and excretion into human breast milk is unknown. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.

    MECHANISM OF ACTION

    Delavirdine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type-1 (HIV-1). It binds directly to reverse transcriptase. This binding blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. Unlike nucleoside reverse transcriptase inhibitors, delavirdine does not compete with template or nucleoside triphosphates nor does it require phosphorylation to be active. HIV-2 reverse transcriptase and human cellular DNA polymerase alpha, gamma, or delta are not inhibited by delavirdine. In addition, HIV-1 group O, a group of highly divergent strains that are uncommon in North America, may not be inhibited by delavirdine. IC50 and IC90 (50% and 90% inhibitory concentrations) for delavirdine against laboratory isolates of HIV-1 ranged from 0.005 to 0.03 micromolar and 0.04 to 0.1 micromolar, respectively. The range of delavirdine IC50 and IC90 values for clinical HIV isolates are 0.001 to 0.69 micromolar (mean 0.038 micromolar) and 0.05 to 0.1 micromolar, respectively. In vitro combination studies show additive to synergistic anti-HIV-1 activity for delavirdine with zidovudine, didanosine, lamivudine, interferon-alfa, and protease inhibitors.
     
    In delavirdine resistant patients, mutations in reverse transcriptase occurred primarily at amino acid position 103 and less frequently at positions 181 and 236. Delavirdine may confer cross-resistance to other NNRTIs when used alone or in combination. Mutations at positions 103 and 181 have been associated with cross-resistance among NNRTIs in vitro.[28476]
     
    Avoid use of delavirdine in patients infected with HIV-2, as HIV-2 is intrinsically resistant to NNRTIs. To identify the HIV strain, The Centers for Disease Control and Prevention guidelines for HIV diagnostic testing recommend initial HIV testing using an HIV-1 and HIV-2 antigen and antibody combination immunoassay and subsequent testing using an HIV-1 and HIV-2 antibody differentiation immunoassay.[46638]

    PHARMACOKINETICS

    Delavirdine is administered orally.
     
    Once in systemic circulation, the plasma protein binding of delavirdine is approximately 98%, primarily to albumin. Concentrations in the cerebrospinal fluid average 0.4% +/- 0.07% of the corresponding plasma concentrations; this is about 20% of the fraction not bound to plasma proteins. Steady-state semen and saliva concentrations are approximately 2% and 6% of the corresponding plasma concentrations, respectively. Delavirdine is extensively metabolized by hepatic cytochrome P450 (CYP) enzymes to several inactive metabolites. The primary enzyme involved is CYP3A; however, in vitro data suggest that the drug may also be metabolized by CYP2D6. The major metabolic pathways are N-desalkylation and pyridine hydroxylation. Delavirdine exhibits nonlinear steady-state elimination pharmacokinetics. The apparent oral clearance decreases by about 22-fold as the total daily dose increases from 60 to 1,200 mg per day. In vitro and in vivo studies have shown that delavirdine reduces the activity of CYP3A and inhibits its own metabolism. In vitro studies have also shown that delavirdine reduces the activity of CYP2C9, CYP2D6, and CYP2C19. CYP3A inhibition is reversible within 1 week after discontinuation of delavirdine therapy. Approximately 44% of the dose is recovered in feces, and approximately 51% of the dose is excreted in the urine. Less than 5% was recovered unchanged in the urine. The apparent plasma half-life increases with dose; mean half-life following 400 mg three times daily is 5.8 hours (range: 2 to 11 hours).
     
    Affected cytochrome P450 isoenzymes: CYP3A4, CYP2D6, CYP2C9, CYP2C10
    Delavirdine is a substrate and a potent inhibitor of CYP3A4, a substrate and an inhibitor of CYP2D6, and an inhibitor of CYP2C9 and CYP2C19. Delavirdine inhibition of CYP3A4 activity appears to be reversible within 1 week after discontinuing the drug.[28476]

    Oral Route

    Delavirdine is rapidly absorbed with peak plasma concentrations occurring at approximately 1 hour. The single-dose bioavailability of the tablets relative to an oral solution in 16 non-HIV-infected subjects was 85% +/- 25%. The single-dose bioavailability of the tablets was increased by approximately 20% when a slurry was prepared by allowing the tablets to disintegrate in water before administration. Delavirdine may be given with or without food. Multiple dosing with food reduces the mean Cmax by approximately 25%; however, AUC and Cmin are not be altered.[28476]