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    Other Cytotoxic Antibiotics

    BOXED WARNING

    Hepatic disease, jaundice

    Liver function tests (LFTs) are recommended before ixabepilone initiation and should be monitored periodically thereafter. Combination therapy with ixabepilone and capecitabine is contraindicated in patients with hepatic disease defined as an AST or ALT more than 2.5 times the upper level of normal (ULN) or a total bilirubin more than 1 times the ULN. Increased ixabepilone systemic exposure occurs in patients with elevated AST or bilirubin, which increases the risk for toxicity and neutropenia. Among patients with an AST or ALT more than 2.5 times ULN or bilirubin more than 1.5 times the  ULN who received both ixabepilone and capecitabine, a greater incidence of grade 3/4 serious adverse reactions, febrile neutropenia, and toxicity-related deaths occurred.  Among patients with baseline AST or ALT more than 2.5 times ULN or bilirubin more than 1.5 times ULN who received monotherapy with ixabepilone, there was a higher incidence of grade 4 neutropenia, febrile neutropenia, and serious adverse effects. Due to the higher frequency of adverse reactions, dose adjustment is necessary in patients receiving ixabepilone monotherapy with mild or moderate hepatic impairment. Ixabepilone monotherapy should not be given to patients with an AST or ALT more than 10 times the ULN and bilirubin over 3 times the ULN or in patients with jaundice. Limited data are available on the use of ixabepilone monotherapy in patients with an AST or ALT more 5 times the ULN; caution is advised. Liver function tests (LFTs) are recommended before ixabepilone initiation and should be monitored periodically thereafter.

    DEA CLASS

    Rx

    DESCRIPTION

    First FDA-approved epothilone antineoplastic agent; microtubule stabilizing agent approved for use with capecitabine in the treatment of metastatic or locally advanced breast cancer that is resistant to an anthracycline and a taxane or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated; also approved as monotherapy for the treatment of metastatic or locally advanced breast cancer that is resistant or refractory to anthracyclines, taxanes, and capecitabine.

    COMMON BRAND NAMES

    Ixempra

    HOW SUPPLIED

    Ixempra Intravenous Inj Pwd F/Sol: 15mg, 45mg

    DOSAGE & INDICATIONS

    For the treatment of breast cancer.
    For the treatment of metastatic or locally advanced breast cancer that is resistant to an anthracycline and a taxane, or that is taxane resistant and for patients whom further anthracycline therapy is contraindicated, in combination with capecitabine.
    NOTE: Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting. Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting.
    Intravenous dosage
    Adults

    40 mg/m2 (maximum BSA, 2.2 m2) IV over 3 hours on day 1, in combination with capecitabine 1,000 mg/m2 PO twice daily (approximately 12 hours apart) within 30 minutes of a meal on days 1 to 14, followed by 1 week of rest. Repeat every 3 weeks. One hour prior to ixabepilone administration on day 1, premedicate with diphenhydramine 50 mg by mouth (or equivalent) and ranitidine 150 mg to 300 mg by mouth (or equivalent) to reduce the risk of hypersensitivity; add dexamethasone 20 mg in patients who have previously had a reaction to ixabepilone. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label clinical trial of patients with anthracycline- and taxane-resistant locally advanced or metastatic breast cancer (n = 752), treatment with ixabepilone plus capecitabine significantly improved the median progression-free survival (PFS) (5.7 months vs. 4.1 months) and objective response rate (34.7% vs. 14.3%) compared with capecitabine alone; the median duration of response was 6.4 months versus 5.6 months, respectively. There was no significant difference in overall survival (12.9 months vs. 11.1 months).[33563]

    For the treatment of metastatic or locally advanced breast cancer that is resistant or refractory to anthracyclines, taxanes, and capecitabine.
    Intravenous dosage
    Adults

    40 mg/m2 (maximum BSA, 2.2 m2) IV over 3 hours on day 1, every 3 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with ixabepilone resulted in an objective response rate of 12.4% by independent review and 18.3% by investigator assessment, for a median duration of 6 months in a multicenter, single-arm study in women with progressive or recurrent locally advanced or metastatic breast cancer (n = 126); all responses were partial. The median time to response was 6.1 weeks.

    MAXIMUM DOSAGE

    Adults

    40 mg/m2 IV over 3 hours, given every 3 weeks. If taking a strong CYP3A4 inhibitor, 20 mg/m2 IV over 3 hours, given every 3 weeks. For patients with a BSA > 2.2 m2, the ixabepilone dose should be calculated for a BSA of 2.2 m2.

    Elderly

    40 mg/m2 IV over 3 hours, given every 3 weeks. If taking a strong CYP3A4 inhibitor, 20 mg/m2 IV over 3 hours, given every 3 weeks. For patients with a BSA > 2.2 m2, the ixabepilone dose should be calculated for a BSA of 2.2 m2.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Ixabepilone monotherapy:
    NOTE: Limited data are available for patients with baseline AST or ALT > 5 x ULN; cautious use is recommended.
    AST and ALT <= 2.5 x ULN and bilirubin <= 1 x ULN: 40 mg/m2 IV over 3 hours every 3 weeks for first cycle. Dose adjustments for subsequent cycles should be based on patient tolerance.
    AST and ALT > 2.5 x ULN and <= 10 x ULN and bilirubin > 1 x ULN and <= 1.5 x ULN: 32 mg/m2 IV over 3 hours every 3 weeks for first cycle. Dose adjustments for subsequent cycles should be based on patient tolerance.
    AST and ALT > 2.5 x ULN and <= 10 x ULN and bilirubin > 1.5 x ULN to <= 3 x ULN: 20—30 mg/m2 IV over 3 hours every 3 weeks for first cycle. Dose adjustments for subsequent cycles should be based on patient tolerance.
    AST or ALT > 10 x ULN or bilirubin > 3 x ULN: Use of ixabepilone is not recommended.
     
    Ixabepilone plus capecitabine:
    AST or ALT <= 2.5 x ULN or bilirubin <= 1 x ULN: 40 mg/m2 IV over 3 hours every 3 weeks.
    AST or ALT > 2.5 x ULN or bilirubin > 1 x ULN: Contraindicated.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    NOTE: Hepatic function assessment is recommended before ixabepilone initiation and periodically thereafter. Use of ixabepilone monotherapy is not recommended for patients with AST or ALT > 10 x the upper limit of normal (ULN) or bilirubin > 3 x ULN. Use of ixabepilone in combination with capecitabine is contraindicated for use by patients with AST or ALT > 2.5 x ULN or bilirubin > 1 x ULN.
    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 1
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
    Emetic Risk
    Pediatrics: Doses 3 to 10 mg/m2: Moderate
    Adults: Low
    Administer routine antiemetic prophylaxis prior to treatment.
    Extravasation Risk
    Irritant

    Injectable Administration

    Visually inspect parenteral products for particular matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Administer as an intravenous infusion.
    Prior to administration of a new cycle, patients should have documented neutrophil counts 1500/mm3 or higher, platelet counts 100,000/mm3 or higher, improvement in nonhematologic toxicity to grade 1 or resolution of the toxicity.
    To help prevent hypersensitivity reactions, premedicate all patients an hour before ixabepilone receipt with an H-1 blocker such as diphenhydramine 50 mg PO or equivalent and a H-2 blocker. Premedicate patients who have experienced a hypersensitivity reaction to ixabepilone with dexamethasone 20 mg IV 30 minutes before ixabepilone receipt or dexamethasone 20 mg PO 60 minutes before ixabepilone receipt in addition to an H-1 blocker and an H-2 blocker. Also, consider extension of the ixabepilone infusion time.
     
    Reconstitution and further dilution:
    Remove the kit from the refrigerator and let stand at room temperature for 30 minutes. Upon removal from the refrigerator, there may be a white precipitate seen in the diluent vial. Once the vial reaches room temperature, the precipitate will dissolve to form a clear solution.
    The 15 mg Ixempra Kit contains two vials: one with ixabepilone and one with 8 mL of diluent. The 45 mg Ixempra Kit also contains two vials: one with ixabepilone and one with 23.5 mL of diluent. To allow for withdrawal losses, the vial labeled as 15 mg ixabepilone for injection contains 16 mg of ixabepilone, and the vial labeled as 45 mg ixabepilone for injection contains 47 mg of ixabepilone.
    Only the diluent supplied in the Ixempra Kit is to be utilized to reconstitute ixabepilone. To reconstitute, withdraw the diluent (8 mL for 15 mg vials and 23.5 mL for 45 mg vials), and slowly inject the solution into the ixabepilone vial. The ixabepilone vial should then be gently swirled and inverted until the powder is completely dissolved. The final concentration of the reconstituted solution is 2 mg/mL. Reconstituted solution should be further diluted as soon as possible but is stable in the vial for up to 1 hour at room temperature and light. Do not keep the reconstituted solution in a syringe.
    The reconstituted solution must be further diluted in a DEHP-free bag. A solution pH range of 6-9 is required to maintain ixabepilone stability. Lactated Ringer's, 0.9% Sodium Chloride (pH adjusted to 6-9 by addition of 2 mEq sodium bicarbonate prior to the addition of ixabepilone), and PLASMA-LYTE A Injection pH 7.4, are the only recommended solutions for dilution. The final concentration of the ixabepilone infusion must be between 0.2 mg/mL and 0.6 mg/mL. After ixabepilone has been added, mix the solution by manual rotation.
    Diluted solutions are stable at room temperature and light for up to 6 hours. Infusion of the diluted solution must be completed with the 6-hour period.
     
    Infusion:
    Use of an in-line filter of 0.2-1.2 micron pore size is required during administration.
    Infusion containers and administration sets must be DEHP-free.
    Administer the dose over 3 hours. Carefully observe patients for a hypersensitivity reaction such as flushing, rash, dyspnea, and bronchospasm.

    STORAGE

    Ixempra:
    - Discard reconstituted product if not used within 6 hours
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 36 to 46 degrees F
    - Store in original package until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Polyoxyethylated castor oil hypersensitivity

    Ixabepilone is contraindicated in patients who have a history of severe polyoxyethylated castor oil hypersensitivity. The supplied diluent that must be used for reconstitution of ixabepilone has 52.8% weight per volume of purified polyoxyethylated castor oil. As hypersensitivity reactions may occur, premedication with both an H1 and H2 blocker should be administered to all patients approximately 1 hour before the ixabepilone infusion. Closely observe patients for symptoms of hypersensitivity reactions such as bronchospasm, dyspnea, flushing, and rash. In the event of a severe hypersensitivity reaction, stop the infusion and give supportive treatment. Any patient who experiences a hypersensitivity reaction with ixabepilone should be premedicated with a corticosteroid in addition to an H1 and H2 blocker before subsequent infusions. In addition, the length of the infusion may be extended.

    Bone marrow suppression, neutropenia, thrombocytopenia

    Ixabepilone is associated with dose-related bone marrow suppression. Ixabepilone is contraindicated in patients with neutropenia defined as a neutrophil count < 1500 cells/mm3 or thrombocytopenia defined as a platelet count < 100,000/mm3. Blood counts should be monitored frequently during treatment. The next cycle of ixabepilone should not be given until neutrophils are >= 1500/mm3 and platelets are >= 100,000/mm3. The ixabepilone dose should be reduced in any patient who experiences severe neutropenia or thrombocytopenia (see Dosage). Ixabepilone should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.

    Hepatic disease, jaundice

    Liver function tests (LFTs) are recommended before ixabepilone initiation and should be monitored periodically thereafter. Combination therapy with ixabepilone and capecitabine is contraindicated in patients with hepatic disease defined as an AST or ALT more than 2.5 times the upper level of normal (ULN) or a total bilirubin more than 1 times the ULN. Increased ixabepilone systemic exposure occurs in patients with elevated AST or bilirubin, which increases the risk for toxicity and neutropenia. Among patients with an AST or ALT more than 2.5 times ULN or bilirubin more than 1.5 times the  ULN who received both ixabepilone and capecitabine, a greater incidence of grade 3/4 serious adverse reactions, febrile neutropenia, and toxicity-related deaths occurred.  Among patients with baseline AST or ALT more than 2.5 times ULN or bilirubin more than 1.5 times ULN who received monotherapy with ixabepilone, there was a higher incidence of grade 4 neutropenia, febrile neutropenia, and serious adverse effects. Due to the higher frequency of adverse reactions, dose adjustment is necessary in patients receiving ixabepilone monotherapy with mild or moderate hepatic impairment. Ixabepilone monotherapy should not be given to patients with an AST or ALT more than 10 times the ULN and bilirubin over 3 times the ULN or in patients with jaundice. Limited data are available on the use of ixabepilone monotherapy in patients with an AST or ALT more 5 times the ULN; caution is advised. Liver function tests (LFTs) are recommended before ixabepilone initiation and should be monitored periodically thereafter.

    Diabetes mellitus, peripheral neuropathy

    In clinical trials, peripheral neuropathy was one of the most commonly reported adverse reactions and most frequent cause of therapy discontinuation. Patients with diabetes mellitus may be at increased risk of severe neuropathy. Neither grade 1 neuropathy at baseline nor a previous history of treatment with a neurotoxic chemotherapeutic agent were found to be a risk factor. Patients with moderate to severe neuropathy, defined as >= grade 2, at baseline were excluded from clinical studies. Caution should be utilized when ixabepilone is administered to patients with diabetes mellitus or moderate to severe (>= grade 2) neuropathy.

    Cardiac arrhythmias, cardiac disease, ventricular dysfunction

    Caution should be utilized when ixabepilone is administered to patients with cardiac disease. Patients receiving combination therapy with ixabepilone and capecitabine had a higher incidence of myocardial ischemia and ventricular dysfunction (1.9%) as compared with patients who received capecitabine monotherapy (0.3%). Cardiac arrhythmias, specifically supraventricular arrhythmias, were not reported in any patient receiving capecitabine monotherapy whereas 0.5% of patients receiving combination therapy had supraventricular arrhythmias. Ixabepilone therapy may need to be discontinued in any patient who develops cardiac ischemia or impaired cardiac function.

    Children

    The safety and efficacy of ixabepilone in pediatric patients (children and adolescents) have not been established.

    Alcoholism, driving or operating machinery, substance abuse

    The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% (w/v)). Consideration should be given to the CNS effects and other effects of alcohol. Special consideration may be prudent in individuals with alcoholism or a history of substance abuse. Patients should be cautioned regarding driving or operating machinery immediately after Ixempra receipt, as the high alcohol content infused over a short period of time may cause impairment.

    Geriatric

    Per the manufacturer, clinical studies did not include a sufficient number of geriatric patients >= 65 years of age to adequately evaluate whether there is any difference in response to therapy between those >= 65 years of age and < 65 years of age. As compared with data from younger patients, patients at least 65 years who got both ixabepilone and capecitabine had a higher incidence of grade 3/4 adverse reactions. Two of 43 patients at least 65 years with no more than mild hepatic impairment at baseline had a toxicity-related death. Among monotherapy recipients, no differences in the ixabepilone safety profile were noted between younger and older patients. However, data are limited.

    Pregnancy

    Ixabepilone is classified as FDA pregnancy risk category D and has been shown to produce toxic effects, including death, in fetal animal studies. There are no data concerning the effects in pregnant women. Therefore, ixabepilone should be avoided during pregnancy, and females of childbearing potential should be instructed to avoid becoming pregnant during ixabepilone therapy. If a woman becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possible of loss of pregnancy.

    Breast-feeding

    Excretion of ixabepilone into human breast milk is not known. In animal studies, ixabepilone was found to be excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants, breast-feeding is not advised, and patients should be instructed to either discontinue breast-feeding or discontinue ixabepilone. Consider the importance of ixabepilone receipt by the mother.

    Radiation therapy

    Patients who have had previous radiation therapy may experience radiation recall reactions during ixabepilone therapy. Radiation recall reactions have been reported among patients receiving ixabepilone in postmarketing experience.

    Vaccination

    Vaccination with live vaccines should be avoided due to the risk of neutropenia during ixabepilone therapy.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 54.0-68.0
    leukopenia / Delayed / 49.0-57.0
    peripheral neuropathy / Delayed / 14.0-23.0
    neuritis / Delayed / 0-21.0
    dysesthesia / Delayed / 0-21.0
    hyporeflexia / Delayed / 0-21.0
    hypoesthesia / Delayed / 0-21.0
    hyperesthesia / Delayed / 0-21.0
    paresthesias / Delayed / 0-21.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 2.0-18.0
    asthenia / Delayed / 13.0-16.0
    fatigue / Early / 13.0-16.0
    anemia / Delayed / 8.0-10.0
    thrombocytopenia / Delayed / 7.0-8.0
    arthralgia / Delayed / 8.0-8.0
    myalgia / Early / 8.0-8.0
    stomatitis / Delayed / 4.0-6.0
    diarrhea / Early / 1.0-6.0
    vomiting / Early / 1.0-4.0
    nausea / Early / 2.0-3.0
    anorexia / Delayed / 2.0-3.0
    musculoskeletal pain / Early / 2.0-3.0
    abdominal pain / Early / 2.0-2.0
    constipation / Delayed / 0-2.0
    rash / Early / 1.0-2.0
    alopecia / Delayed / 0-2.0
    dehydration / Delayed / 1.0-2.0
    dizziness / Early / 0-1.0
    headache / Early / 0-1.0
    gastroesophageal reflux / Delayed / 0-1.0
    pruritus / Rapid / 0-1.0
    dyspnea / Early / 1.0-1.0
    edema / Delayed / 0-1.0
    chest pain (unspecified) / Early / 1.0-1.0
    insomnia / Early / 0-1.0
    fever / Early / 1.0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    intracranial bleeding / Delayed / Incidence not known
    coagulopathy / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    atrial flutter / Early / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    thromboembolism / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known

    Moderate

    hot flashes / Early / 5.0-6.0
    lymphopenia / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    gastritis / Delayed / Incidence not known
    dysphonia / Delayed / Incidence not known
    hypoxia / Early / Incidence not known
    pneumonitis / Delayed / Incidence not known
    trismus / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    angina / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    radiation recall reaction / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known
    hypovolemia / Early / Incidence not known
    hypokalemia / Delayed / Incidence not known
    bleeding / Early / Incidence not known

    Mild

    dysgeusia / Early / 6.0-12.0
    weight loss / Delayed / 6.0-11.0
    skin hyperpigmentation / Delayed / 2.0-11.0
    infection / Delayed / 4.0-6.0
    cough / Delayed / 2.0-6.0
    lacrimation / Early / 4.0-5.0
    lethargy / Early / Incidence not known
    syncope / Early / Incidence not known
    laryngitis / Delayed / Incidence not known
    weakness / Early / Incidence not known
    chills / Rapid / Incidence not known
    flushing / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Propoxyphene: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as propoxyphene should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose
    Alfentanil: (Minor) Alfentanil is an inhibitor of P-glycoprotein (Pgp). Ixabepilone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp inhibitor may cause an increase in ixabepilone concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Amiodarone: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as amiodarone has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with amiodarone; closely monitor patients for ixabepilone-related toxicities.
    Amitriptyline: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Amitriptyline is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in amitriptyline concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Amlodipine; Atorvastatin: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Atorvastatin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in atorvastatin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Amobarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as clarithromycin should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Amprenavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as amprenavir should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Apalutamide: (Major) Avoid coadministration of ixabepilone with apalutamide due to decreased plasma concentrations of ixabepilone; consider an alternative to apalutamide with no or minimal CYP3A4 induction potential. If concomitant use is unavoidable, the dose of ixabepilone may be gradually increased as tolerated from 40 mg/m2 to 60 mg/m2 IV over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ixabepilone exposure by 43%.
    Aprepitant, Fosaprepitant: (Major) Use caution if ixabepilone and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ixabepilone-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ixabepilone is 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 increase plasma concentrations of ixabepilone. 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.
    Asciminib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with asciminib is necessary; consider the use of an alternative agent to asciminib that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and asciminib is a weak CYP3A inhibitor. The effect of weak CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Atazanavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as atazanavir should be avoided. Alternative therapies that do not inhibit the CYP3A4 should be considered. If concurrent treatment with atazanavir is necessary, strongly consider reducing the adult ixabepilone dose to 20 mg/m2 every 3 weeks; this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors (no clinical data are available). Closely monitor patients for ixabepilone-related toxicities. If atazanavir is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of cobicistat with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If cobicistat is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Cobicistat is a strong CYP3A4 inhibitor and a P-glycoprotein (P-gp) inhibitor, while ixabepilone is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%. (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as atazanavir should be avoided. Alternative therapies that do not inhibit the CYP3A4 should be considered. If concurrent treatment with atazanavir is necessary, strongly consider reducing the adult ixabepilone dose to 20 mg/m2 every 3 weeks; this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors (no clinical data are available). Closely monitor patients for ixabepilone-related toxicities. If atazanavir is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Atorvastatin: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Atorvastatin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in atorvastatin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Atorvastatin; Ezetimibe: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Atorvastatin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in atorvastatin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Avacopan: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with avacopan is necessary; consider the use of an alternative agent to avacopan that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and avacopan is a weak CYP3A inhibitor. The effect of weak CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Barbiturates: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Belumosudil: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with belumosudil is necessary; consider the use of an alternative agent to belumosudil that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and belumosudil is a weak CYP3A inhibitor. The effect of weak CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Bepridil: (Minor) Bepridil is an inhibitor of P-glycoprotein (Pgp). Ixabepilone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp inhibitor may cause an increase in ixabepilone concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Berotralstat: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with berotralstat is necessary; consider the use of an alternative agent to berotralstat that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Bexarotene: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as bexarotene may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Bicalutamide: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with bicalutamide is necessary; consider the use of an alternative agent to bicalutamide that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Contraindicated) Medications with significant alcohol content should not be administered during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% w/v). Administration of ixabepilone to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Contraindicated) Medications with significant alcohol content should not be administered during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% w/v). Administration of ixabepilone to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering ixabepilone with boceprevir due to an increased potential for ixabepilone-related adverse events. If ixabepilone 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 pathway of ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ixabepilone plasma concentrations.
    Bosentan: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as bosentan may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Budesonide: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Budesonide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in budesonide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Budesonide; Formoterol: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Budesonide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in budesonide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Budesonide; Glycopyrrolate; Formoterol: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Budesonide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in budesonide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Bupivacaine; Meloxicam: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, meloxicam may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential. Monitor closely for bleeding.
    Butabarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Butalbital; Acetaminophen: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Butalbital; Acetaminophen; Caffeine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Carbamazepine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as carbamazepine may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Carvedilol: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Carvedilol is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in carvedilol concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Ceritinib: (Major) Avoid coadministration of ceritinib with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If ceritinib is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Ixabepilone is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Chloramphenicol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as chloramphenicol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Chlordiazepoxide; Amitriptyline: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Amitriptyline is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in amitriptyline concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Ciprofloxacin: (Moderate) Caution is recommended if ixabepilone is coadministered with ciprofloxacin; closely monitor patients for ixabepilone-related toxicities, such as peripheral neuropathy, GI effects, or myelosuppression. Ixabepilone is a CYP3A4 substrate, and concomitant use with moderate CYP3A4 inhibitors such as ciprofloxacin has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered.
    Clarithromycin: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as clarithromycin should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Cobicistat: (Major) Avoid coadministration of cobicistat with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If cobicistat is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Cobicistat is a strong CYP3A4 inhibitor and a P-glycoprotein (P-gp) inhibitor, while ixabepilone is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Colchicine: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Colchicine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in colchicine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Conivaptan: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone and for other acute ixabepilone-related adverse reactions if coadministration with conivaptan is necessary; consider the use of an alternative agent to conivaptan that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. The effect of moderate CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Crizotinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with crizotinib is necessary; consider the use of an alternative agent to crizotinib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor. The effect of moderate CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Cyclosporine: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as cyclosporine should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose
    Danazol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as danazol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Darunavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors, such as darunavir, 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 dose of ixabepilone to 20 mg/m2 every 3 weeks; there are no clinical data with this dose adjustment. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Darunavir; Cobicistat: (Major) Avoid coadministration of cobicistat with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If cobicistat is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Cobicistat is a strong CYP3A4 inhibitor and a P-glycoprotein (P-gp) inhibitor, while ixabepilone is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%. (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors, such as darunavir, 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 dose of ixabepilone to 20 mg/m2 every 3 weeks; there are no clinical data with this dose adjustment. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of cobicistat with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If cobicistat is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Cobicistat is a strong CYP3A4 inhibitor and a P-glycoprotein (P-gp) inhibitor, while ixabepilone is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%. (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors, such as darunavir, 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 dose of ixabepilone to 20 mg/m2 every 3 weeks; there are no clinical data with this dose adjustment. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) If possible, avoid coadministration of ixabepilone with ritonavir; concurrent use is expected to result in increased ixabepilone plasma concentrations and risk of adverse events. Consider alternative therapies before using ixabepilone with ritonavir. If coadministration of ixabepilone with ritonavir cannot be avoided, consider an ixabepilone dosage reduction to 20 mg/m2 IV over 3 hours given every 3 weeks, as this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors. Carefully monitor for adverse events. If a patient is already receiving ritonavir, a washout period of approximately 1 week is recommended before starting ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this enzyme.
    Delavirdine: (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.
    Desogestrel; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Dexamethasone: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as dexamethasone may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Dextromethorphan; Quinidine: (Minor) Quinidine is an inhibitor of and substrate for P-glycoprotein (Pgp). Ixabepilone is a mild inhibitor of and substrate for Pgp. Concomitant use of these agents may cause an increase in ixabepilone concentrations and/or an increase in quinidine concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and ixabepilone together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Digoxin: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Digoxin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in digoxin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Diltiazem: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as diltiazem should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Disulfiram: (Contraindicated) The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% w/v). Administration of ixabepilone to patients receiving or who have recently received disulfiram may result in disulfiram-like reactions.
    Docetaxel: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Docetaxel is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in docetaxel concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Doxorubicin Liposomal: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Doxorubicin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in doxorubicin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Doxorubicin: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Doxorubicin is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in doxorubicin concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Dronedarone: (Major) Dronedarone is metabolized by and is an inhibitor of CYP3A. Ixabepilone is a substrate for CYP3A4. In addition, ixabepilone is a P-glycoprotein (Pgp) substrate and dronedarone is a Pgp inhibitor. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Droperidol: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Droperidol is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in droperidol concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Drospirenone; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Duvelisib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with duvelisib is necessary; consider the use of an alternative agent to duvelisib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Efavirenz: (Moderate) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as efavirenz may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers or inhibitors are coadministered with ixabepilone; alternative therapies should be considered.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as efavirenz may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers or inhibitors are coadministered with ixabepilone; alternative therapies should be considered.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as efavirenz may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers or inhibitors are coadministered with ixabepilone; alternative therapies should be considered.
    Elbasvir; Grazoprevir: (Moderate) Administering ixabepilone with elbasvir; grazoprevir may result in elevated ixabepilone plasma concentrations. Ixabepilone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eletriptan: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Eletriptan is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in eletriptan concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with ivacaftor is necessary; consider the use of an alternative agent to ivacaftor that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and ivacaftor is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of cobicistat with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If cobicistat is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Cobicistat is a strong CYP3A4 inhibitor and a P-glycoprotein (P-gp) inhibitor, while ixabepilone is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of cobicistat with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If cobicistat is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Cobicistat is a strong CYP3A4 inhibitor and a P-glycoprotein (P-gp) inhibitor, while ixabepilone is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Enzalutamide: (Major) Avoid coadministration of ixabepilone with enzalutamide due to decreased plasma concentrations of ixabepilone; consider an alternative to enzalutamide with no or minimal CYP3A4 induction potential. If concomitant use is unavoidable, the dose of ixabepilone may be gradually increased as tolerated from 40 mg/m2 to 60 mg/m2 IV over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ixabepilone exposure by 43%.
    Erythromycin: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as erythromycin has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with erythromycin; closely monitor patients for ixabepilone-related toxicities.
    Erythromycin; Sulfisoxazole: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as erythromycin has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with erythromycin; closely monitor patients for ixabepilone-related toxicities.
    Ethanol: (Major) The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% w/v). Additive drowsiness may occur if a patient drinks alcohol immediately before or after getting ixabepilone.
    Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Ethinyl Estradiol; Norelgestromin: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Ethinyl Estradiol; Norgestrel: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Etonogestrel; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Everolimus: (Moderate) Monitor for an increase in acute ixabepilone-related adverse reactions if coadministration with everolimus is necessary (e.g., frequently monitor peripheral blood counts between cycles). Ixabepilone is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on ixabepilone exposure has not been studied; however, concomitant use may increase plasma concentrations of ixabepilone.
    Fedratinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with fedratinib is necessary; consider the use of an alternative agent to fedratinib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Fenofibrate: (Minor) Fenofibrate is an inhibitor of P-glycoprotein (Pgp). Ixabepilone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp inhibitor may cause an increase in ixabepilone concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Fexofenadine: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Fexofenadine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in fexofenadine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Fexofenadine; Pseudoephedrine: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Fexofenadine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in fexofenadine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Fluconazole: (Moderate) Caution is recommended if ixabepilone is coadministered with fluconazole; closely monitor patients for ixabepilone-related toxicities, such as peripheral neuropathy, GI effects, or myelosuppression. Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as fluconazole has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered.
    Fluoxetine: (Moderate) Fluoxetine is a mild CYP3A4 inhibitor. Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with mild or moderate CYP3A4 inhibitors has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with fluoxetine; closely monitor patients for ixabepilone-related toxicities.
    Fluvoxamine: (Moderate) The effect on the exposure to ixabepilone, a CYP3A4 substrate, during coadministration of weak or moderate CYP3A4 inhibitors has not been studied. Caution is recommended during coadministration of a moderate CYP3A4 inhibitor such as fluvoxamine. Alternative agents that do not inhibit CYP3A4 should be considered. Patients receiving CYP3A4 inhibitors should be monitored closely for acute toxicities (e.g., frequent monitoring of peripheral blood counts between cycles of ixabepilone).
    Fosamprenavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as fosamprenavir should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider reducing the adult ixabepilone dose to 20 mg/m2 every 3 weeks; clinical data with 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
    Fosphenytoin: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers may lead to reduced and subtherapeutic concentrations of ixabepilone. Fosphenytoin is a prodrug of phenytoin, and phenytoin is a strong CYP3A4 inducer. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Fostamatinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with fostamatinib is necessary; consider the use of an alternative agent to fostamatinib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and fostamatinib is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Glyburide: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Glyburide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in glyburide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Glyburide; Metformin: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Glyburide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in glyburide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Grapefruit juice: (Contraindicated) Ixabepilone is a CYP3A4 substrate, and grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level. In addition, ixabepilone is a P-glycoprotein (Pgp) substrate and grapefruit juice is a Pgp inhibitor. Grapefruit juice may increase ixabepilone concentrations and should be avoided.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ixabepilone, a CYP3A substrate, as ixabepilone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Imatinib: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as imatinib, STI-571 should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Indinavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as indinavir should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider reducing the adult ixabepilone dose to 20 mg/m2 every 3 weeks; clinical data for this dose adjustment is lacking. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose. Closely monitor patients for ixabepilone-related toxicities.
    Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with ixabepilone may result in increased serum concentrations of ixabepilone. Ixabepilone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution and close monitoring are advised if these drugs are used together.
    Isoniazid, INH: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with isoniazid is necessary; consider the use of an alternative agent to isoniazid that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as rifampin may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered. (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with isoniazid is necessary; consider the use of an alternative agent to isoniazid that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Isoniazid, INH; Rifampin: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as rifampin may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered. (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with isoniazid is necessary; consider the use of an alternative agent to isoniazid that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Istradefylline: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with istradefylline 40 mg daily is necessary; consider the use of an alternative agent to istradefylline that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Itraconazole: (Major) Avoid coadministration of ixabepilone and itraconazole due to the potential for increased ixabepilone exposure. If coadministration cannot be avoided, consider a dose reduction of ixabepilone to 20 mg/m2. If itraconazole is discontinued, a washout period of approximately 1 week should be allowed before the ixabepilone dose is adjusted upward to the indicated dose. Itraconazole is a strong CYP3A4 inhibitor; ixabepilone is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased ixabepilone AUC by 79% compared to ixabepilone treatment alone.
    Ivacaftor: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with ivacaftor is necessary; consider the use of an alternative agent to ivacaftor that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and ivacaftor is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Ketoconazole: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ketoconazole should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as clarithromycin should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Lapatinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with lapatinib is necessary; consider the use of an alternative agent to lapatinib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and lapatinib is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Larotrectinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with larotrectinib is necessary; consider the use of an alternative agent to larotrectinib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and larotrectinib is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Lefamulin: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with oral lefamulin is necessary; consider the use of an alternative agent to oral lefamulin that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. The effect of moderate CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ixabepilone; monitor for potential reduction in efficacy. Ixabepilone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ixabepilone; monitor for potential reduction in efficacy. Ixabepilone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with letermovir is necessary. Avoid coadministration in patients also receiving cyclosporine, because the magnitude of this interaction may be amplified. If concurrent use of ixabepilone and both letermovir and cyclosporine is unavoidable, consider reducing the adult ixabepilone dose to 20 mg/m2. If letermovir or cyclosporine is discontinued, a washout period of approximately 1 week should be allowed before the ixabepilone dose is adjusted upwards to the indicated dose. Ixabepilone is a substrate of 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. Concurrent administration with a strong CYP3A4 inhibitor increased ixabepilone exposure (AUC) by 79%. The effect of mild and moderate CYP3A4 inhibitors on ixabepilone exposure has not been evaluated.
    Levoketoconazole: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ketoconazole should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose
    Levonorgestrel; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Lonafarnib: (Major) Avoid coadministration of lonafarnib with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If lonafarnib is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Ixabepilone is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Loperamide: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Loperamide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in loperamide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Loperamide; Simethicone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Loperamide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in loperamide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Lopinavir; Ritonavir: (Major) If possible, avoid coadministration of ixabepilone with ritonavir; concurrent use is expected to result in increased ixabepilone plasma concentrations and risk of adverse events. Consider alternative therapies before using ixabepilone with ritonavir. If coadministration of ixabepilone with ritonavir cannot be avoided, consider an ixabepilone dosage reduction to 20 mg/m2 IV over 3 hours given every 3 weeks, as this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors. Carefully monitor for adverse events. If a patient is already receiving ritonavir, a washout period of approximately 1 week is recommended before starting ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this enzyme.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of ixabepilone; avoid concurrent use if possible. Ixabepilone is primarily metabolized by CYP3A4, and lumacaftor is a strong CYP3A inducer. If coadministration is necessary and appropriate alternative agents are not available, FDA-approved labeling for ixabepilone suggests to gradually increase the ixabepilone dose from 40 mg/m2 to 60 mg/m2 depending on tolerance once the patient is maintained on lumacaftor; ivacaftor. If the ixabepilone dose is increased, it should be given as a 4-hour infusion and the patient monitored closely for toxicity. If lumacaftor; ivacaftor is subsequently discontinued, the ixabepilone dose should be reduced to the dose used prior to its initiation. It should be noted that this recommendation is based on extrapolation from a drug interaction study with rifampin; there is not clinical data with this dosage adjustment in patients receiving other strong CYP3A inducers. Coadministration of ixabepilone with rifampin, another strong CYP3A inducer, decreased ixabepilone AUC by 43%. Ixabepilone is also a substrate of the P-glycoprotein (P-gp) drug transporter; in vitro data suggests lumacaftor; ivacaftor may induce and/or inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear.
    Lumacaftor; Ivacaftor: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with ivacaftor is necessary; consider the use of an alternative agent to ivacaftor that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and ivacaftor is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Maraviroc: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Maraviroc is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in maraviroc concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Maribavir: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with maribavir is necessary; consider the use of an alternative agent to maribavir that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and maribavir is a weak CYP3A inhibitor. The effect of weak CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Mefloquine: (Minor) Mefloquine is an inhibitor of and substrate for P-glycoprotein (Pgp). Ixabepilone is a mild inhibitor of and substrate for Pgp. Concomitant use of these agents may cause an increase in ixabepilone concentrations and/or an increase in mefloquine concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Meloxicam: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, meloxicam may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential. Monitor closely for bleeding.
    Mephobarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Methadone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Methadone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in methadone concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Methohexital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Metronidazole: (Contraindicated) Medications with significant alcohol content should not be administered during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% w/v). Administration of ixabepilone to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions.
    Mifepristone: (Moderate) Caution should be used when administering mild or moderate CYP3A4 inhibitors during treatment with ixabepilone, and alternative therapeutic agents that do not inhibit CYP3A4 should be considered. Patients receiving CYP3A4 inhibitors during treatment with ixabepilone should be monitored closely for acute toxicities (e.g., frequent monitoring of peripheral blood counts between cycles of ixabepilone). In some patients, a dose reduction of ixabepilone should be considered. Ixabepilone is a CYP3A4 substrate, and mifepristone is a CYP3A4 inhibitor. If mifepristone is discontinued, allow 7 days to elapse before increasing the ixabepilone dose; the prolonged action of mifepristone may result in prolonged duration of any interactions.
    Mitotane: (Major) Concomitant use of mitotane with ixabepilone should be undertaken with caution as it could result in decreased plasma concentrations of ixabepilone, leading to reduced efficacy; a gradual dose adjustment may be necessary. If possible, consider the use of a drug with lower enzyme induction potential. Mitotane is a strong CYP3A4 inducer and ixabepilone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of ixabepilone.
    Modafinil: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as modafinil may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Morphine: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (P-gp). Morphine is a P-gp substrate, and concomitant use may cause an increase in morphine concentrations. Use caution if ixabepilone is coadministered with morphine and monitor for an increase in side effects.
    Morphine; Naltrexone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (P-gp). Morphine is a P-gp substrate, and concomitant use may cause an increase in morphine concentrations. Use caution if ixabepilone is coadministered with morphine and monitor for an increase in side effects.
    Nabumetone: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, nabumetone may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential. Monitor closely for bleeding.
    Nafcillin: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as nafcillin may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Nanoparticle Albumin-Bound Sirolimus: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Sirolimus is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in sirolimus concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Nefazodone: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as nefazodone should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Nelfinavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as nelfinavir 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 IV every 3 weeks; clinical data to support this dose adjustment are 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.
    Nevirapine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers, such as nevirapine, may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Nicardipine: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors like nicardipine has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with nicardipine; closely monitor patients for ixabepilone-related toxicities.
    Nirmatrelvir; Ritonavir: (Major) If possible, avoid coadministration of ixabepilone with ritonavir; concurrent use is expected to result in increased ixabepilone plasma concentrations and risk of adverse events. Consider alternative therapies before using ixabepilone with ritonavir. If coadministration of ixabepilone with ritonavir cannot be avoided, consider an ixabepilone dosage reduction to 20 mg/m2 IV over 3 hours given every 3 weeks, as this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors. Carefully monitor for adverse events. If a patient is already receiving ritonavir, a washout period of approximately 1 week is recommended before starting ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this enzyme.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Norethindrone; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Norgestimate; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Nortriptyline: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Nortriptyline is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in nortriptyline concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Olanzapine; Fluoxetine: (Moderate) Fluoxetine is a mild CYP3A4 inhibitor. Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with mild or moderate CYP3A4 inhibitors has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with fluoxetine; closely monitor patients for ixabepilone-related toxicities.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) If possible, avoid coadministration of ixabepilone with ritonavir; concurrent use is expected to result in increased ixabepilone plasma concentrations and risk of adverse events. Consider alternative therapies before using ixabepilone with ritonavir. If coadministration of ixabepilone with ritonavir cannot be avoided, consider an ixabepilone dosage reduction to 20 mg/m2 IV over 3 hours given every 3 weeks, as this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors. Carefully monitor for adverse events. If a patient is already receiving ritonavir, a washout period of approximately 1 week is recommended before starting ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this enzyme.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of ixabepilone with rifabutin due to decreased plasma concentrations of ixabepilone; consider an alternative to rifabutin with no or minimal CYP3A induction potential. If concomitant use is unavoidable, the dose of ixabepilone may be gradually increased as tolerated from 40 mg/m2 to 60 mg/m2 IV over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A substrate and rifabutin is a CYP3A inducer.
    Ondansetron: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Ondansetron is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in ondansetron concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Oritavancin: (Major) Ixabepilone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of ixabepilone may be reduced if these drugs are administered concurrently. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Osilodrostat: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with osilodrostat is necessary; consider the use of an alternative agent to osilodrostat that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and osilodrostat is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Paclitaxel: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Paclitaxel is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in paclitaxel concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Pacritinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with pacritinib is necessary; consider the use of an alternative agent to pacritinib that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor. The effect of weak CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Palbociclib: (Moderate) Frequently monitor peripheral blood counts between ixabepilone cycles and watch for an increase in ixabepilone-related adverse reactions if coadministration with palbociclib is necessary; consider substituting an agent that does not inhibit CYP3A4 for palbociclib if appropriate. Palbociclib is a weak time-dependent inhibitor of CYP3A and ixabepilone is a CYP3A4 substrate. The effect of mild CYP3A4 inhibitors on exposure to ixabepilone has not been studied; however, the ixabepilone manufacturer recommends caution with concurrent use.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ixabepilone, a CYP3A4 substrate, may cause an increase in systemic concentrations of ixabepilone. Use caution when administering these drugs concomitantly.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentobarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Perphenazine; Amitriptyline: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Amitriptyline is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in amitriptyline concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Phenobarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Phenytoin: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as phenytoin may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Posaconazole: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as posaconazole should be avoided. In addition, ixabepilone is a P-glycoprotein (P-gp) substrate and posaconazole is a P-gp inhibitor. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Prednisone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Prednisone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in prednisone concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Primidone: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Probenecid; Colchicine: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Colchicine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in colchicine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Propafenone: (Minor) Propafenone is an inhibitor of P-glycoprotein (Pgp). Ixabepilone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp inhibitor may cause an increase in ixabepilone concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Propoxyphene: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as propoxyphene should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose
    Quinidine: (Minor) Quinidine is an inhibitor of and substrate for P-glycoprotein (Pgp). Ixabepilone is a mild inhibitor of and substrate for Pgp. Concomitant use of these agents may cause an increase in ixabepilone concentrations and/or an increase in quinidine concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Ranolazine: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as ranolazine has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with ranolazine; closely monitor patients for ixabepilone-related toxicities.
    Ribociclib: (Major) Avoid coadministration of ribociclib with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If ribociclib is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Ixabepilone is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If ribociclib is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Ixabepilone is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Rifabutin: (Major) Avoid coadministration of ixabepilone with rifabutin due to decreased plasma concentrations of ixabepilone; consider an alternative to rifabutin with no or minimal CYP3A induction potential. If concomitant use is unavoidable, the dose of ixabepilone may be gradually increased as tolerated from 40 mg/m2 to 60 mg/m2 IV over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A substrate and rifabutin is a CYP3A inducer.
    Rifampin: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as rifampin may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Rifapentine: (Major) Avoid coadministration of ixabepilone with rifapentine due to decreased plasma concentrations of ixabepilone; consider an alternative to rifapentine with no or minimal CYP3A4 induction potential. If concomitant use is unavoidable, the dose of ixabepilone may be gradually increased as tolerated from 40 mg/m2 to 60 mg/m2 IV over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ixabepilone exposure by 43%.
    Ritonavir: (Major) If possible, avoid coadministration of ixabepilone with ritonavir; concurrent use is expected to result in increased ixabepilone plasma concentrations and risk of adverse events. Consider alternative therapies before using ixabepilone with ritonavir. If coadministration of ixabepilone with ritonavir cannot be avoided, consider an ixabepilone dosage reduction to 20 mg/m2 IV over 3 hours given every 3 weeks, as this dose is predicted to adjust the ixabepilone AUC to the range observed without inhibitors. Carefully monitor for adverse events. If a patient is already receiving ritonavir, a washout period of approximately 1 week is recommended before starting ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is a potent inhibitor of this enzyme.
    Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Rubella Virus Vaccine Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Rucaparib: (Major) Consider the use of an agent that does not inhibit CYP3A4 if treatment with ixabepilone is necessary. If concomitant use of rucaparib with ixabepilone is unavoidable, monitor for an increase in ixabepilone-related adverse reactions (e.g., frequent monitoring of peripheral blood counts between cycles of ixabepilone). Ixabepilone is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor. The effect of mild or moderate CYP3A4 inhibitors on ixabepilone exposure has not been studied.
    Saquinavir: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as saquinavir should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider reducing the ixabepilone dose to 20 mg/m2 given every 3 weeks; clinical data for this dose adjustment are 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.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Secobarbital: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Segesterone Acetate; Ethinyl Estradiol: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as ethinyl estradiol should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Selpercatinib: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with selpercatinib is necessary; consider the use of an alternative agent to selpercatinib that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and selpercatinib is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Simeprevir: (Moderate) Simeprevir is a mild intestinal CYP3A4 inhibitor. Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with mild or moderate CYP3A4 inhibitors has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with a mild or moderate CYP3A4 inhibitor; closely monitor patients for ixabepilone-related toxicities, such as periopheral neuropathy, GI effects, and musculoskeletal effects.
    Sirolimus: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Sirolimus is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in sirolimus concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Spironolactone: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with spironolactone is necessary; consider the use of an alternative agent to spironolactone that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with spironolactone is necessary; consider the use of an alternative agent to spironolactone that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    St. John's Wort, Hypericum perforatum: (Contraindicated) Avoid concurrent use of ixabepilone and St. John's Wort. St. John's Wort may decrease ixabepilone concentrations unpredictably.
    Streptogramins: (Moderate) Monitor for an increase in acute ixabepilone-related adverse reactions if coadministration with dalfopristin; quinupristin is necessary (e.g., frequently monitor peripheral blood counts between cycles). Ixabepilone is a CYP3A4 substrate and dalfopristin; quinupristin is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on ixabepilone exposure has not been studied; however, concomitant use may increase plasma concentrations of ixabepilone.
    Tacrolimus: (Minor) Tacrolimus is an inhibitor of P-glycoprotein (Pgp). Ixabepilone is a Pgp substrate, and concomitant use of ixabepilone with a Pgp inhibitor may cause an increase in ixabepilone concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering ixabepilone with telaprevir due to an increased potential for ixabepilone-related adverse events. If ixabepilone 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 pathway of ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ixabepilone plasma concentrations.
    Telithromycin: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as telithromycin should be avoided. In addition, ixabepilone is a P-glycoprotein (Pgp) substrate and telithromycin is a Pgp inhibitor. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.
    Teniposide: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Teniposide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in teniposide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Tezacaftor; Ivacaftor: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with ivacaftor is necessary; consider the use of an alternative agent to ivacaftor that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and ivacaftor is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Thiopental: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Trandolapril; Verapamil: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as verapamil has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with verapamil; closely monitor patients for ixabepilone-related toxicities.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Tucatinib: (Major) Avoid coadministration of tucatinib with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If tucatinib is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Ixabepilone is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Verapamil: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as verapamil has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with verapamil; closely monitor patients for ixabepilone-related toxicities.
    Viloxazine: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with viloxazine is necessary; consider the use of an alternative agent to viloxazine that does not inhibit CYP3A4. Ixabepilone is a CYP3A4 substrate and viloxazine is a weak CYP3A4 inhibitor. The effect of weak CYP3A4 inhibitors on exposure to ixabepilone has not been studied.
    Vincristine Liposomal: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Vincristine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in vincristine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Vincristine: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Vincristine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in vincristine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Voriconazole: (Major) Avoid coadministration of voriconazole with ixabepilone if possible due to increased ixabepilone exposure. If concomitant use is unavoidable, consider reducing the dose of ixabepilone to 20 mg/m2. If voiconazole is discontinued, resume the original dose of ixabepilone after a washout period of approximately 1 week. Ixabepilone is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ixabepilone exposure by 79%.
    Voxelotor: (Moderate) Frequently monitor peripheral blood counts between cycles of ixabepilone, and for other acute ixabepilone-related adverse reactions if coadministration with voxelotor is necessary; consider the use of an alternative agent to voxelotor that does not inhibit CYP3A. Ixabepilone is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. The effect of moderate CYP3A inhibitors on exposure to ixabepilone has not been studied.
    Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Zafirlukast: (Major) Ixabepilone is a CYP3A4 substrate, and concomitant use of ixabepilone with strong CYP3A4 inhibitors such as zafirlukast should be avoided. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction. Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose.

    PREGNANCY AND LACTATION

    Pregnancy

    Ixabepilone is classified as FDA pregnancy risk category D and has been shown to produce toxic effects, including death, in fetal animal studies. There are no data concerning the effects in pregnant women. Therefore, ixabepilone should be avoided during pregnancy, and females of childbearing potential should be instructed to avoid becoming pregnant during ixabepilone therapy. If a woman becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possible of loss of pregnancy.

    Excretion of ixabepilone into human breast milk is not known. In animal studies, ixabepilone was found to be excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants, breast-feeding is not advised, and patients should be instructed to either discontinue breast-feeding or discontinue ixabepilone. Consider the importance of ixabepilone receipt by the mother.

    MECHANISM OF ACTION

    Ixabepilone is a microtubule stabilizing agent. Microtubules are important cellular structures that are involved in cell division; intact microtubule function is required for the mitotic spindle formation and function. Formation of microtubules involves polymerization of heterodimeric alpha/beta- tubulin subunits. Polymerization of the heterodimeric subunits involves hydrolysis of guanosine 5'-triphosphate and is regulated by several microtubule-associated proteins. Normally, a dynamic equilibrium of microtubule polymerization and depolymerization exists. Ixabepilone directly binds to beta-tubulin subunits on microtubules and promotes tubulin polymerization and microtubule stabilization via inhibition of depolymerization. Microtubule stabilization leads to microtubule bundles, and the formation of microtubule bundles is plasma ixabepilone concentration-dependent. Alterations in spindle formation cause G2/M phase cell cycle arrest, which causes apoptosis. In addition to direct antitumor activity from cell cycle arrest, ixabepilone has antiangiogenic activity. Normally, microtubules modulate interactions with growth factors.
     
    Ixabepilone appears to have a low susceptibility to various mechanisms involved in the development of tumor resistance. Ixabepilone possesses low in vitro susceptibility to multiple tumor resistance mechanisms including efflux transporters such as MRP-l and P-glycoprotein (P-gp). In vivo, ixabepilone has antitumor activity against multiple human tumor xenografts including drug-resistant types that harbor tubulin mutations or overexpress P-gp, MRP-1, and beta-III tubulin isoforms. Ixabepilone is active in xenografts that are resistant to multiple agents including taxanes, anthracyclines, and vinca alkaloids. In vivo, ixabepilone demonstrated synergistic antitumor activity in combination with capecitabine.

    PHARMACOKINETICS

    Ixabepilone is administered intravenously as an infusion. 
     
    The primary route of metabolism is oxidation via the hepatic cytochrome P450 (CYP) isoenzyme CYP3A4. Most ixabepilone is eliminated as metabolites; over 30 inactive metabolites have been identified. Renal excretion accounts for a small proportion of the elimination. Of the administered dose, 1.6% of unchanged drug was excreted in the feces and 5.6% in the urine. The elimination half-life is approximately 52 hours. Within 7 days of administration, 65% of the dose is excreted in the feces and 21% in the urine. Ixabepilone accumulation in the plasma is not expected when the drug is administered every 3 weeks.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
     
    Ixabepilone is a substrate of CYP3A4. In vitro, it is also a substrate and weak inhibitor of P-gp. Ixabepilone has not been found to inhibit CYP enzymes and is not expected to alter the plasma concentrations of other drugs. Concurrent administration of ixabepilone and capecitabine resulted in a 19% decrease in ixabepilone Cmax, a 27% decrease in capecitabine Cmax, and a 14% increase in 5-fluorouracil. This interaction was not found to be clinically significant.

    Intravenous Route

    At the end of a 3 hour infusion of 40 mg/m2, the mean peak plasma concentration was 252 ng/mL, and the mean AUC was 2143 ng/mL. Ixabepilone exhibited linear pharmacokinetics after one hour infusions of doses between 7.4 mg/m2 and 59.2 mg/m2. Ixabepilone is 67—77% protein bound and, after a 40 mg/m2 dose, has a mean volume of distribution of > 1000 L. Based on the large volume of distribution, ixabepilone may extensively distribute into the extravascular spaces.