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  • CLASSES

    Small Molecule Antineoplastic Colony Stimulating Factor-1 Receptor (CSF-1R) Inhibitors

    BOXED WARNING

    Hepatic disease, hepatotoxicity

    Severe and fatal hepatotoxicity has been reported with pexidartinib therapy; avoid use in patients with pre-existing hepatic disease (e.g., elevated hepatic enzymes; hyperbilirubinemia; or active liver or biliary tract disease). Monitor liver function tests including AST, ALT, total bilirubin, direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase levels prior to starting pexidartinib, weekly for the first 8 weeks, every 2 weeks for the next month, and then every 3 months thereafter. Avoid coadministration with other drugs known to cause hepatotoxicity. Additionally, do not administer pexidartinib with a meal or snack; food increases pexidartinib exposure which may increase the risk of hepatotoxicity. All prescribers, pharmacies, and patients must be certified or enrolled in the TURALIO REMS program to prescribe, dispense, or receive pexidartinib due to the risk of hepatotoxicity. Information about the drug and the program can be found at www.turalioREMS.com or by calling 1-833-887-2546. Therapy interruption, dose reduction, and/or discontinuation may be necessary in patients who develop hepatic toxicity. LFT abnormalities may recur following drug rechallenge with a reduced pexidartinib dosage; monitor LFTs weekly for the first month after rechallenge.[64535]

    DEA CLASS

    Rx

    DESCRIPTION

    Colony-stimulating factor-1 receptor inhibitor
    Used for adults with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to surgery
    Boxed warning for serious and potentially fatal liver injury; routine LFT monitoring is required; prescribers, pharmacies, and patients must be certified/enrolled in the TURALIO REMS program

    COMMON BRAND NAMES

    Turalio

    HOW SUPPLIED

    Turalio Oral Cap: 200mg

    DOSAGE & INDICATIONS

    For the treatment of tenosynovial giant cell tumor.
    NOTE: The FDA has designated pexidartinib as an orphan drug for the treatment of giant cell tumor of the tendon sheath.
    For the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery.
    Oral dosage
    Adults

    400 mg orally twice daily on an empty stomach until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy, a dosage reduction, or discontinuation may be necessary in patients who develop severe toxicity or intolerable side effects.[64535] The overall response rate at 25 weeks was significantly improved in patients with advanced tenosynovial giant cell tumor (TGCT) who received pexidartinib compared with placebo (39% vs. 0%; p less than 0.0001) in a multinational, randomized, double-blind, phase 3 trial (n = 120; the ENLIVEN trial). At a median follow-up of 22 months (range, 0 to 25 months), the median duration of response had not been reached in the pexidartinib arm. Patients in this trial were eligible if they had symptomatic TGCT and surgical resection would be associated with a risk of worsening function or severe morbidity.[64537]

    MAXIMUM DOSAGE

    Adults

    800 mg/day PO.

    Geriatric

    800 mg/day PO.

    Adolescents

    Safety and efficacy not established.

    Children

    Safety and efficacy not established.

    Infants

    Safety and efficacy not established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is recommended in patients with mild hepatic impairment (total bilirubin level at the upper limit of normal (ULN) or less with an AST level greater than the ULN OR total bilirubin greater than 1- to 1.5-times the ULN with any AST level); the recommended dosage in patients with moderate (total bilirubin level greater than 1.5- to 3-times the ULN and any AST level) or severe (total bilirubin level greater than 3- to 10-times the ULN and any AST level) hepatic impairment has not been established. However, pexidartinib use in patients with pre-existing hepatic disease (e.g., increased serum transaminase levels; total bilirubin or direct bilirubin levels greater than the upper limit of normal (ULN); or active liver or biliary tract disease, including increased alkaline phosphatase (ALP) level) is not recommended.
    Management of Treatment-Related Hepatotoxicity
    Recommended Dose Reductions
    First dose reduction: 200 mg PO in the morning and 400 mg PO in the evening.Second dose reduction: 200 mg PO twice daily; permanently discontinue therapy in patients unable to tolerate 200 mg PO twice daily.
    Increased ALT and/or AST levels greater than 3- to 5-times the ULN: Hold pexidartinib therapy and monitor liver function tests (LFTs) weekly. If AST and ALT levels decrease to 3-times the ULN or less within 4 weeks, resume therapy at a reduced dose. Permanently discontinue therapy if AST and ALT levels do not decrease to 3-times the ULN or less in 4 weeks.Increased ALT and/or AST levels greater than 5- to 10-times the ULN: Hold pexidartinib therapy and monitor LFTs twice weekly. If AST and ALT levels decrease to 3-times the ULN or less within 4 weeks, resume therapy at a reduced dose. Permanently discontinue therapy if AST and ALT levels do not decrease to 3-times the ULN or less in 4 weeks.Increased ALT and/or AST levels greater than 10-times the ULN: Permanently discontinue therapy. Monitor LFTs twice weekly until AST and ALT levels decrease to 5-times the ULN or less and then weekly until AST and ALT levels decrease to 3-times the ULN or less.
    Increased ALP AND gamma-glutamyl transferase levels greater than 2-times the ULN: Permanently discontinue therapy. Monitor LFTs twice weekly until the ALP level decreases to 5-times the ULN or less and then weekly until the ALP level decreases to 2-times the ULN or less.
    Increased total bilirubin level greater than the ULN to less than 2-times the ULN OR direct bilirubin level greater than the ULN and less than 1.5-times the ULN: Hold pexidartinib therapy and monitor LFTs twice weekly. If an alternate cause for hyperbilirubinemia is confirmed and bilirubin levels decrease to less than the ULN within 4 weeks, resume therapy at a reduced dose. Permanently discontinue therapy if bilirubin levels do not decrease to less than the ULN in 4 weeks.Increased total bilirubin level of 2-times the ULN or greater OR direct bilirubin level greater than 1.5-times the ULN: Permanently discontinue therapy. Monitor LFTs twice weekly until bilirubin levels decrease to the ULN or less.[64535]

    Renal Impairment

    Reduce the pexidartinib dosage to 200 mg PO in the morning and 400 mg PO in the evening in patients with mild to severe renal impairment (creatinine clearance of 15 to 89 mL/min using the Cockcroft-Gault formula and actual body weight).[64535]

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Take pexidartinib on an empty stomach at least 1 hour before or 2 hours after a meal or snack.
    Swallow whole; do not open, break, or chew capsules.
    Do not take with grapefruit juice.
    Separate the pexidartinib dose from acid-reducing medicines; take pexidartinib either 2 hours before or after antacids or at least 2 hours before or 10 hours after H2 blockers.
    If a dose is missed or if vomiting occurs after a dose, skip that dose and take the next dose at the scheduled time.[64535]

    STORAGE

    Turalio:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hepatic disease, hepatotoxicity

    Severe and fatal hepatotoxicity has been reported with pexidartinib therapy; avoid use in patients with pre-existing hepatic disease (e.g., elevated hepatic enzymes; hyperbilirubinemia; or active liver or biliary tract disease). Monitor liver function tests including AST, ALT, total bilirubin, direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase levels prior to starting pexidartinib, weekly for the first 8 weeks, every 2 weeks for the next month, and then every 3 months thereafter. Avoid coadministration with other drugs known to cause hepatotoxicity. Additionally, do not administer pexidartinib with a meal or snack; food increases pexidartinib exposure which may increase the risk of hepatotoxicity. All prescribers, pharmacies, and patients must be certified or enrolled in the TURALIO REMS program to prescribe, dispense, or receive pexidartinib due to the risk of hepatotoxicity. Information about the drug and the program can be found at www.turalioREMS.com or by calling 1-833-887-2546. Therapy interruption, dose reduction, and/or discontinuation may be necessary in patients who develop hepatic toxicity. LFT abnormalities may recur following drug rechallenge with a reduced pexidartinib dosage; monitor LFTs weekly for the first month after rechallenge.[64535]

    Renal impairment

    An initial pexidartinib dosage reduction is recommended in patients with mild to severe renal impairment (creatinine clearance of 15 to 89 mL/min using the Cockcroft-Gault formula and actual body weight).

    Pregnancy

    Pexidartinib may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid becoming pregnant while receiving pexidartinib. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. In animal studies, embryo-fetal toxicities including localized fetal edema, absence of kidney and ureter, abnormalities of the reproductive tract, and developmental variations such as misshapen kidney, decreased skeletal ossification, and slightly or moderately malaligned sternebrae were observed in rats and absence of kidney or ureter, misshapen or malpositioned kidney, rib abnormalities, and skeletal variations of accessory skull bones were observed in rabbits at pexidartinib doses that resulted in maternal exposures that were about equal to the human exposure at the recommended dose of 800 mg.[64535]

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during pexidartinib treatment. Pregnancy testing should be performed prior to starting pexidartinib in female patients of reproductive potential. These patients should use effective non-hormonal contraception and avoid pregnancy during and for 1 month after pexidartinib therapy. Concomitant use of pexidartinib and hormonal contraceptives may decrease the effectiveness of hormonal contraceptives. Women who become pregnant while receiving pexidartinib should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during and for 1 week after therapy due to the risk of male-mediated teratogenicity. Based on animal studies, pexidartinib may cause infertility in males and females.

    Breast-feeding

    No information is available regarding the presence of pexidartinib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Due to the potential for serious adverse reactions in the nursing child, breast-feeding is not recommended during therapy or for at least 1 week after the last pexidartinib dose.[64535]

    ADVERSE REACTIONS

    Severe

    elevated hepatic enzymes / Delayed / 0-20.0
    hepatotoxicity / Delayed / 0-10.0
    visual impairment / Early / 0-10.0
    hypertension / Early / 4.9-4.9
    hypercholesterolemia / Delayed / 4.9-4.9
    hyperbilirubinemia / Delayed / 0-3.3
    hypophosphatemia / Delayed / 3.3-3.3
    neutropenia / Delayed / 3.3-3.3
    rash / Early / 1.6-1.6
    vomiting / Early / 1.6-1.6
    lymphopenia / Delayed / 1.6-1.6
    papilledema / Delayed / Incidence not known

    Moderate

    anemia / Delayed / 30.0-30.0
    peripheral edema / Delayed / 20.0-20.0
    thrombocytopenia / Delayed / 15.0-15.0
    constipation / Delayed / 12.0-12.0
    cholangitis / Delayed / 0-10.0
    photophobia / Early / 0-10.0
    blurred vision / Early / 0-10.0
    peripheral neuropathy / Delayed / 10.0-10.0
    memory impairment / Delayed / 0-10.0
    confusion / Early / 0-10.0
    amnesia / Delayed / 0-10.0
    oral ulceration / Delayed / 0-10.0
    stomatitis / Delayed / 0-10.0
    erythema / Early / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    edema / Delayed / Incidence not known

    Mild

    hair discoloration / Delayed / 67.0-67.0
    fatigue / Early / 64.0-64.0
    dysgeusia / Early / 26.0-26.0
    pruritus / Rapid / 18.0-18.0
    anorexia / Delayed / 16.0-16.0
    skin hypopigmentation / Delayed / 0-10.0
    alopecia / Delayed / 0-10.0
    skin hyperpigmentation / Delayed / 0-10.0
    diplopia / Early / 0-10.0
    hyperactivity / Early / 0-10.0
    xerostomia / Early / 0-10.0
    fever / Early / 0-10.0
    acneiform rash / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    maculopapular rash / Early / Incidence not known
    malaise / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    blepharedema / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with pexidartinib. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Abemaciclib: (Major) Avoid coadministration of pexidartinib with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of dihydrocodeine as needed. If pexidartinib is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Pexidartinib is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with pexidartinib can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Acetaminophen; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of oxycodone as needed. If pexidartinib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with pexidartinib is necessary. If pexidartinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like pexidartinib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Aliskiren; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Allopurinol: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with allopurinol. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Aluminum Hydroxide: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Amiodarone: (Major) Avoid coadministration of pexidartinib with amiodarone as concurrent use may increase pexidartinib exposure and the risk of adverse events; concomitant use may also decrease amiodarone plasma concentrations. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Additionally, monitor for decreased efficacy of amiodarone. If amiodarone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of amiodarone. Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with amiodarone. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; amiodarone is a CYP3A4 substrate and moderate CYP3A4 inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A4 inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Amlodipine; Atorvastatin: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine. (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with atorvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Amlodipine; Benazepril: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Amlodipine; Celecoxib: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Amlodipine; Olmesartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Amlodipine; Valsartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of pexidartinib with clarithromycin as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Antacids: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Apalutamide: (Major) Avoid coadministration of pexidartinib with apalutamide as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Aprepitant, Fosaprepitant: (Major) Avoid coadministration of pexidartinib with aprepitant, fosaprepitant as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If aprepitant is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of aprepitant. Pexidartinib is a CYP3A substrate. Aprepitant is a moderate CYP3A inhibitor when administered as a 3-day regimen (125 mg/80 mg/80 mg). When administered as a single oral or single intravenous dose, the inhibitor effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of dihydrocodeine as needed. If pexidartinib is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Pexidartinib is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with pexidartinib can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Aspirin, ASA; Omeprazole: (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of oxycodone as needed. If pexidartinib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Atazanavir: (Major) Avoid coadministration of pexidartinib with atazanavir as concurrent use may increase exposure to pexidartinib and decrease exposure to atazanavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of atazanavir efficacy. If atazanavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of atazanavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 and UGT substrate; atazanavir is a strong CYP3A4 inhibitor and a UGT inhibitor. Additionally, pexidartinib is a moderate CYP3A4 inducer and atazanavir is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%; coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. Decreased antiretroviral concentrations may lead to a reduction of antiviral efficacy and the potential for development of viral resistance.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of pexidartinib with atazanavir as concurrent use may increase exposure to pexidartinib and decrease exposure to atazanavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of atazanavir efficacy. If atazanavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of atazanavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 and UGT substrate; atazanavir is a strong CYP3A4 inhibitor and a UGT inhibitor. Additionally, pexidartinib is a moderate CYP3A4 inducer and atazanavir is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%; coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. Decreased antiretroviral concentrations may lead to a reduction of antiviral efficacy and the potential for development of viral resistance. (Major) Avoid coadministration of pexidartinib with cobicistat as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If cobicistat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cobicistat. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cobicistat is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Atogepant: (Major) Use an atogepant dose of 30 or 60 mg PO once daily if coadministered with pexidartinib. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
    Atorvastatin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with atorvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Atorvastatin; Ezetimibe: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with atorvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Auranofin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with auranofin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Avacopan: (Major) Avoid concomitant use of avacopan and pexidartinib due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
    Avanafil: (Major) Coadministration of avanafil with pexidartinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
    Avapritinib: (Major) Avoid coadministration of avapritinib with pexidartinib due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
    Axitinib: (Major) Avoid coadministration of axitinib with pexidartinib if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Azathioprine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with azathioprine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Bedaquiline: (Major) Avoid coadministration of pexidartinib with bedaquiline due to decreased plasma exposure to bedaquiline. Bedaquiline is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased bedaquiline exposure by approximately 20%. The AUC and Cmax of the primary metabolite of bedaquiline (M2) were increased by 70% and 80%, respectively.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid coadministration of pexidartinib with phenobarbital as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Brigatinib: (Major) Avoid coadministration of brigatinib with pexidartinib due to decreased plasma exposure to brigatinib, which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with pexidartinib, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of pexidartinib, resume the brigatinib dose that was tolerated prior to initiation of pexidartinib. Brigatinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
    Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and pexidartinib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; pexidartinib is a moderate inducer of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with pexidartinib is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If pexidartinib is discontinued, consider a buprenorphine dose reduction, and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer.
    Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with pexidartinib is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If pexidartinib is discontinued, consider a buprenorphine dose reduction, and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer.
    Buspirone: (Moderate) Monitor for decreased efficacy of buspirone if pexidartinib is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Busulfan: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with busulfan. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Cabotegravir; Rilpivirine: (Moderate) Coadministration of rilpivirine with pexidartinib may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Cannabidiol: (Major) Avoid coadministration of pexidartinib with cannabidiol as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If cannabidiol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cannabidiol. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; cannabidiol is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Capmatinib: (Major) Avoid coadministration of capmatinib and pexidartinib due to the risk of decreased capmatinib exposure which may reduce its efficacy. Capmatinib is a CYP3A substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
    Carbamazepine: (Major) Avoid coadministration of pexidartinib with carbamazepine as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and carbamazepine may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Cariprazine: (Major) Coadministration of cariprazine with pexidartinib is not recommended as the net effect of CYP3A4 induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration of cariprazine with CYP3A4 inducers has not been evaluated.
    Ceritinib: (Major) Avoid coadministration of pexidartinib with ceritinib as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ceritinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ceritinib. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Chloramphenicol: (Major) Avoid coadministration of pexidartinib with chloramphenicol as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If chloramphenicol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of chloramphenicol. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Chlorpheniramine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of dihydrocodeine as needed. If pexidartinib is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Pexidartinib is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with pexidartinib can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of dihydrocodeine as needed. If pexidartinib is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Pexidartinib is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with pexidartinib can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Chlorpromazine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with chlorpromazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    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.
    Cimetidine: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Ciprofloxacin: (Major) Avoid coadministration of pexidartinib with ciprofloxacin as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If ciprofloxacin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ciprofloxacin. Pexidartinib is a CYP3A substrate; ciprofloxacin is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Clarithromycin: (Major) Avoid coadministration of pexidartinib with clarithromycin as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Clozapine: (Moderate) Monitor for loss of clozapine effectiveness if coadministered with pexidartinib. Consideration should be given to increasing the clozapine dose if necessary. When pexidartinib is discontinued, reduce the clozapine dose based on clinical response. Pexidartinib is a moderate inducer of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine.
    Cobicistat: (Major) Avoid coadministration of pexidartinib with cobicistat as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If cobicistat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cobicistat. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cobicistat is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Cobimetinib: (Major) Avoid coadministration of cobimetinib with pexidartinib as concurrent use may decrease cobimetinib exposure, which may reduce its efficacy. Cobimetinib is a CYP3A4 substrate and pexidartinib is a moderate inducer of CYP3A4. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A4 inducer.
    Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Codeine; Guaifenesin: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Codeine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If pexidartinib is discontinued, consider a dose reduction of codeine, and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Pexidartinib is a moderate CYP3A4 inducer. Concomitant use with pexidartinib can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Conivaptan: (Major) Avoid coadministration of pexidartinib with conivaptan as concomitant use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If conivaptan is discontinued, increase the pexidartinib dose to the original dose after three plasma half-lives of conivaptan. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase pexidartinib exposure by 67% at steady state.
    Crizotinib: (Major) Avoid coadministration of pexidartinib with crizotinib as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If crizotinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of crizotinib. Pexidartinib is a CYP3A substrate; crizotinib is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Cyclosporine: (Major) Avoid coadministration of pexidartinib with cyclosporine as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Additionally, closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate as concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. If cyclosporine is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cyclosporine. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cyclosporine is a CYP3A4 substrate and moderate CYP3A4 inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A4 inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Daclatasvir: (Major) Increase the dose of daclatasvir to 90 mg PO once daily if coadministered with pexidartinib due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer reduced the daclatasvir AUC by 63%.
    Danazol: (Major) Avoid coadministration of pexidartinib with danazol as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If danazol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of danazol. Pexidartinib is a CYP3A substrate; danazol is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Dantrolene: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with dantrolene. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with pexidartinib is necessary. Dapsone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
    Darifenacin: (Moderate) Monitor for decreased efficacy of darifenacin if coadministration with pexidartinib is necessary; coadministration may result in decreased plasma concentrations of darifenacin. pexidartinib is a moderate CYP3A4 inducer and darifenacin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of darifenacin.
    Darunavir: (Major) Avoid coadministration of pexidartinib with darunavir as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of darunavir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If darunavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of darunavir. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; darunavir is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Darunavir; Cobicistat: (Major) Avoid coadministration of pexidartinib with cobicistat as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If cobicistat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cobicistat. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cobicistat is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. (Major) Avoid coadministration of pexidartinib with darunavir as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of darunavir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If darunavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of darunavir. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; darunavir is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of pexidartinib with cobicistat as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If cobicistat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cobicistat. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cobicistat is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. (Major) Avoid coadministration of pexidartinib with darunavir as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of darunavir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If darunavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of darunavir. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; darunavir is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of paritaprevir with pexidartinib is contraindicated due to the potential for decreased paritaprevir concentrations and the potential development of viral resistance. Paritaprevir is metabolized by CYP3A4 and pexidartinib is a moderate CYP3A4 inducer. (Major) Avoid coadministration of pexidartinib with dasabuvir as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If dasabuvir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of dasabuvir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; dasabuvir is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. (Major) Avoid coadministration of pexidartinib with ombitasvir as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ombitasvir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ombitasvir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; ombitasvir is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. (Major) Avoid coadministration of pexidartinib with ritonavir as concurrent use may increase exposure to pexidartinib and decrease exposure to ritonavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of ritonavir efficacy. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Deflazacort: (Major) Avoid concomitant use of deflazacort and pexidartinib. Concurrent use may significantly decrease concentrations of 21-desDFZ , the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; pexidartinib is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of another strong CYP3A4 inducer resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
    Delavirdine: (Major) Avoid coadministration of pexidartinib with delavirdine as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of delavirdine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If delavirdine is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of delavirdine. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; delavirdine is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Desogestrel; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Dexamethasone: (Minor) A dose adjustment of systemic dexamethasone may be necessary if pexidartinib is initiated or withdrawn during therapy. Pexidartinib may increase the metabolism of dexamethasone resulting in decreased exposure. Pexidartinib is a moderate inducer of CYP3A4; dexamethasone is a CYP3A4 substrate.
    Dextromethorphan; Quinidine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with quinidine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Diazepam: (Moderate) Monitor patients for decreased efficacy of diazepam if coadministration with pexidartinib is necessary. Concurrent use may decrease diazepam exposure. Diazepam is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer.
    Diclofenac: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with diclofenac. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Diclofenac; Misoprostol: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with diclofenac. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Didanosine, ddI: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with didanosine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Dienogest; Estradiol valerate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of dihydrocodeine as needed. If pexidartinib is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Pexidartinib is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with pexidartinib can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Diltiazem: (Major) Avoid coadministration of pexidartinib with diltiazem as concurrent use may increase pexidartinib exposure and the risk of adverse events; additionally, decreased plasma concentrations of diltiazem may occur. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Monitor blood pressure and heart rate and adjust the diltiazem dose based on clinical response. If diltiazem is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of diltiazem. Pexidartinib is a moderate CYP3A4 inducer and CYP3A4 substrate; diltiazem is a moderate CYP3A inhibitor and CYP3A4 substrate. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Diphenhydramine; Ibuprofen: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Disulfiram: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with disulfiram. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Dolutegravir: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with pexidartinib. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Dolutegravir; Lamivudine: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with pexidartinib. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Dolutegravir; Rilpivirine: (Moderate) Coadministration of rilpivirine with pexidartinib may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with pexidartinib. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Doravirine: (Moderate) Concurrent administration of doravirine and pexidartinib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and pexidartinib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
    Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with pexidartinib due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
    Doxorubicin: (Major) Avoid coadministration of doxorubicin with pexidartinib due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
    Dronabinol: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with pexidartinib is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
    Dronedarone: (Major) Avoid coadministration of pexidartinib with dronedarone as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If dronedarone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of dronedarone. Pexidartinib is a CYP3A substrate; dronedarone is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Drospirenone: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Drospirenone; Estetrol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Drospirenone; Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Drospirenone; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Duvelisib: (Major) Avoid concomitant use of duvelisib with pexidartinib. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Concurrent use may also increase pexidartinib exposure and the risk of adverse events. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. Also, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. When pexidartinib has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with pexidartinib. If duvelisib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of duvelisib. Duvelisib is a CYP3A substrate and a moderate CYP3A inhibitor. Pexidartinib is a CYP3A substrate and a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Efavirenz: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with efavirenz. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with efavirenz. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with efavirenz. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Elbasvir; Grazoprevir: (Major) Coadministration of elbasvir with pexidartinib is not recommended due to decreased exposure of elbasvir, resulting in decreased virologic response. Elbasvir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. (Major) Coadministration of grazoprevir with pexidartinib is not recommended due to decreased exposure of grazoprevir, resulting in decreased virologic response. Grazoprevir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Elvitegravir: (Moderate) Coadministration of elvitegravir with pexidartinib may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of pexidartinib with cobicistat as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If cobicistat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cobicistat. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cobicistat is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. (Moderate) Coadministration of elvitegravir with pexidartinib may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of pexidartinib with cobicistat as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If cobicistat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cobicistat. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; cobicistat is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. (Moderate) Coadministration of elvitegravir with pexidartinib may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of rilpivirine with pexidartinib may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of rilpivirine with pexidartinib may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Encorafenib: (Major) Avoid coadministration of encorafenib and pexidartinib due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
    Entrectinib: (Major) Avoid coadministration of entrectinib with pexidartinib due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
    Enzalutamide: (Major) Avoid coadministration of pexidartinib with enzalutamide as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Erdafitinib: (Major) If coadministration of erdafitinib and pexidartinib is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If pexidartinib must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If pexidartinib is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Erlotinib: (Major) Avoid coadministration of pexidartinib with erlotinib as concurrent use may increase pexidartinib exposure or decrease erlotinib exposure, reducing its efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). The dose of pexidartinib also needs to be reduced. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If erlotinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of erlotinib. Pexidartinib is a UGT substrate and moderate CYP3A4 inducer; erlotinib is a CYP3A4 substrate and UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Erythromycin: (Major) Avoid coadministration of pexidartinib with erythromycin as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If erythromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of erythromycin. Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with erythromycin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A substrate; erythromycin is a moderate CYP3A inhibitor.
    Erythromycin; Sulfisoxazole: (Major) Avoid coadministration of pexidartinib with erythromycin as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If erythromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of erythromycin. Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with erythromycin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A substrate; erythromycin is a moderate CYP3A inhibitor.
    Esomeprazole: (Major) Avoid coadministration of pexidartinib with esomeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of esomeprazole decreased pexidartinib exposure by 50%.
    Estradiol; Levonorgestrel: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Estradiol; Norethindrone: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Estradiol; Norgestimate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ethinyl Estradiol; Norelgestromin: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many non-oral combination contraceptives (injectable, transdermal, and implantable contraceptives) are metabolized by CYP3A. (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ethinyl Estradiol; Norgestrel: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Etonogestrel: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many non-oral combination contraceptives (injectable, transdermal, and implantable contraceptives) are metabolized by CYP3A.
    Etonogestrel; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many non-oral combination contraceptives (injectable, transdermal, and implantable contraceptives) are metabolized by CYP3A. (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if coadministration with pexidartinib is necessary. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations.
    Ezetimibe; Simvastatin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with simvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Famotidine: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Famotidine; Ibuprofen: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%. (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Fedratinib: (Major) Avoid coadministration of fedratinib with pexidartinib as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Concurrent use may also increase pexidartinib exposure and the risk of adverse events. Fedratinib is a CYP3A4 substrate and moderate CYP3A4 inhibitor; pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer. The coadministration of fedratinib with a moderate CYP3A4 inducer has not been evaluated. Based on modeling and simulation data, coadministration with another moderate CYP3A4 inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of pexidartinib is necessary. If pexidartinib is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like pexidartinib with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Finerenone: (Major) Avoid concurrent use of finerenone and pexidartinib due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
    Flibanserin: (Major) Coadministration of flibanserin with pexidartinib is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%.
    Floxuridine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with floxuridine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Fluconazole: (Major) Avoid coadministration of pexidartinib with fluconazole as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If fluconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of fluconazole. Pexidartinib is a CYP3A substrate; fluconazole is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with fluconazole was predicted to increase the pexidartinib exposure by 67%.
    Flurazepam: (Moderate) Monitor patients for decreased efficacy of flurazepam if coadministration with pexidartinib is necessary. Concurrent use may decrease flurazepam exposure. Flurazepam is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer.
    Flutamide: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with flutamide. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Fluvoxamine: (Major) Avoid coadministration of pexidartinib with fluvoxamine as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If fluvoxamine is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of fluvoxamine. Pexidartinib is a CYP3A substrate; fluvoxamine is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Fosamprenavir: (Major) Avoid coadministration of pexidartinib with fosamprenavir as concurrent use may increase exposure to pexidartinib and decrease exposure to fosamprenavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of fosamprenavir efficacy. If fosamprenavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of fosamprenavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and fosamprenavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Fosphenytoin: (Major) Avoid coadministration of pexidartinib with fosphenytoin as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and fosphenytoin may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Gemfibrozil: (Major) Avoid coadministration of pexidartinib with gemfibrozil as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If gemfibrozil is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of gemfibrozil. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; gemfibrozil is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Glecaprevir; Pibrentasvir: (Major) Avoid coadministration of pexidartinib with glecaprevir as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of glecaprevir resulting in the potential loss of efficacy of glecaprevir. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If glecaprevir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of glecaprevir. Pexidartinib is a UGT substrate and moderate CYP3A4 inducer; glecaprevir is a CYP3A4 substrate and UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. (Major) Avoid coadministration of pexidartinib with pibrentasvir as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If pibrentasvir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of pibrentasvir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; pibrentasvir is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Grapefruit juice: (Major) Advise patients to avoid coadministration of pexidartinib with grapefruit juice as concurrent use may increase pexidartinib exposure. Pexidartinib is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    H2-blockers: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Hydralazine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with hydralazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with hydralazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with hydralazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with methyldopa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Hydrocodone; Ibuprofen: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with pexidartinib is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If pexidartinib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease hydrocodone levels.
    Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with pexidartinib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
    Ibuprofen: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Ibuprofen; Oxycodone: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of oxycodone as needed. If pexidartinib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Ibuprofen; Pseudoephedrine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ibuprofen. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Idelalisib: (Major) Avoid coadministration of pexidartinib with idelalisib as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If idelalisib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of idelalisib. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with pexidartinib is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; pexidartinib is a moderate CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
    Imatinib: (Major) Avoid coadministration of pexidartinib with imatinib as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If imatinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of imatinib. Pexidartinib is a CYP3A substrate; imatinib is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Indinavir: (Major) Avoid coadministration of pexidartinib with indinavir as concurrent use may increase pexidartinib exposure. Concurrent use may also result in decreased plasma concentrations of indinavir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Although specific recommendations are unavailable for use with pexidartinib, an increased indinavir dose is recommended (i.e., 1,000 mg PO every 8 hours) when coadministered with other moderate CYP3A4 inducers. If indinavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of indinavir. Pexidartinib is a CYP3A4 and UGT substrate and moderate CYP3A4 inducer; indinavir is a CYP3A4 substrate, strong CYP3A4 inhibitor, and UGT inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%; coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Infigratinib: (Major) Avoid concurrent use of infigratinib and pexidartinib. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Infliximab: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with infliximab. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Alfa-2a: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon alfa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Alfa-2b: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon alfa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Alfa-2b; Ribavirin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon alfa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Alfacon-1: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon alfa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Alfa-n3: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon alfa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Beta-1a: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon beta. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Interferon Beta-1b: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon beta. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Isavuconazonium: (Major) Avoid coadministration of pexidartinib with isavuconazonium as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If isavuconazonium is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of isavuconazonium. Pexidartinib is a CYP3A substrate; isavuconazonium is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Isoniazid, INH: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with isoniazid. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of pexidartinib with rifampin as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and rifampin may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased pexidartinib exposure by 65%. (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with isoniazid. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with pyrazinamide. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Isoniazid, INH; Rifampin: (Major) Avoid coadministration of pexidartinib with rifampin as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and rifampin may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased pexidartinib exposure by 65%. (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with isoniazid. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Isradipine: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with pexidartinib is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Itraconazole: (Major) Avoid coadministration of pexidartinib with itraconazole as concurrent use may increase exposure to pexidartinib and decrease exposure to itraconazole. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of itraconazole efficacy. If itraconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of itraconazole. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and itraconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Ketoconazole: (Major) Avoid coadministration of pexidartinib with ketoconazole as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ketoconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ketoconazole. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 and UGT substrate; ketoconazole is a strong CYP3A4 inhibitor and a UGT inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%; coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Lansoprazole: (Major) Avoid coadministration of pexidartinib with lansoprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of pexidartinib with clarithromycin as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. (Major) Avoid coadministration of pexidartinib with lansoprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Lansoprazole; Naproxen: (Major) Avoid coadministration of pexidartinib with lansoprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Lefamulin: (Major) Avoid coadministration of pexidartinib with oral lefamulin as concurrent use may increase pexidartinib exposure and the risk of adverse events. Concurrent use may also decrease both oral and IV exposure to lefamulin, reducing efficacy. If concurrent use of pexidartinib with oral lefamulin cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily; do not reduce the dose of pexidartinib if given with IV lefamulin. If oral lefamulin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of lefamulin. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer. Lefamulin is a CYP3A4 substrate and the oral formulation is a moderate CYP3A4 inhibitor; IV lefamulin is not expected to inhibit CYP3A4. Based on modeling and simulation data, coadministration with another moderate CYP3A4 inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Lemborexant: (Major) Avoid coadministration of lemborexant and pexidartinib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
    Lesinurad; Allopurinol: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with allopurinol. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Letermovir: (Major) Avoid coadministration of pexidartinib with letermovir as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If letermovir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of letermovir. Pexidartinib is a CYP3A substrate. Letermovir is a moderate CYP3A inhibitor; however, when given with cyclosporine, the combined effect of CYP3A substrates is similar to a strong CYP3A strong inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Leuprolide; Norethindrone: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Levamlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Levoketoconazole: (Major) Avoid coadministration of pexidartinib with ketoconazole as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ketoconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ketoconazole. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 and UGT substrate; ketoconazole is a strong CYP3A4 inhibitor and a UGT inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%; coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Levonorgestrel: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Levonorgestrel; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Lonafarnib: (Contraindicated) Concurrent use of lonafarnib and pexidartinib is contraindicated as use may decrease lonafarnib exposure and efficacy. Pexidartinib exposure and the risk for pexidartinib-related adverse effects may also be increased. If concurrent use is necessary, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate and moderate CYP3A4 inducer; lonafarnib is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of pexidartinib with ritonavir as concurrent use may increase exposure to pexidartinib and decrease exposure to ritonavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of ritonavir efficacy. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Lorlatinib: (Major) Avoid concomitant use of lorlatinib and pexidartinib due to decreased plasma concentrations of lorlatinib, which may reduce its efficacy. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Lorlatinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of pexidartinib with lumacaftor; ivacaftor as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of pexidartinib with lumacaftor; ivacaftor as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Lumateperone: (Major) Avoid coadministration of lumateperone and pexidartinib as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Although data are unavailable for moderate CYP3A4 inducers, coadministration with a strong CYP3A4 inducer significantly decreased lumateperone exposure.
    Lurasidone: (Moderate) If lurasidone is used with pexidartinib, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more) with pexidartinib. Concurrent use may lead to a decrease in efficacy of lurasidone. Pexidartinib is a moderate CYP3A4 inducer; lurasidone is a CYP3A4 substrate.
    Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and pexidartinib due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
    Magnesium Hydroxide: (Moderate) Administer pexidartinib 2 hours before or after locally-acting antacids as concurrent administration may reduce pexidartinib exposure. Although the effects of locally-acting antacids on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Maraviroc: (Moderate) Be aware of the potential for decreased plasma concentrations of maraviroc if coadministration with pexidartinib is necessary, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Maraviroc is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Mefloquine: (Moderate) Use mefloquine with caution if coadministration with pexidartinib is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Mercaptopurine, 6-MP: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with mercaptopurine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Mestranol; Norethindrone: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with pexidartinib is necessary. Consider increasing the dose of methadone as needed. If pexidartinib is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A4; pexidartinib is a moderate CYP3A4 inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Methotrexate: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with methotrexate. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Methyldopa: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with methyldopa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Mifepristone: (Major) Avoid coadministration of pexidartinib with mifepristone as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If mifepristone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of mifepristone. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Minocycline: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with minocycline. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Mitotane: (Major) Avoid coadministration of pexidartinib with mitotane as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Mobocertinib: (Major) Avoid concomitant use of mobocertinib and pexidartinib. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
    Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with pexidartinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for loss of efficacy of sirolimus during coadministration of pexidartinib; a sirolimus dose adjustment may be necessary. Sirolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; pexidartinib is a moderate CYP3A4 inducer.
    Naproxen; Esomeprazole: (Major) Avoid coadministration of pexidartinib with esomeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of esomeprazole decreased pexidartinib exposure by 50%.
    Nefazodone: (Major) Avoid coadministration of pexidartinib with nefazodone as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If nefazodone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of nefazodone. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Nelfinavir: (Major) Avoid coadministration of pexidartinib with nelfinavir as concurrent use may increase exposure to pexidartinib and decrease exposure to nelfinavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of nelfinavir efficacy. If nelfinavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of nelfinavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and nelfinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Neratinib: (Major) Avoid concomitant use of pexidartinib with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of pexidartinib with netupitant as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If netupitant is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of netupitant. Pexidartinib is a CYP3A substrate; netupitant is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Nevirapine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with nevirapine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Niacin; Simvastatin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with simvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Nilotinib: (Major) Avoid coadministration of pexidartinib with nilotinib as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If nilotinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of nilotinib. Pexidartinib is a CYP3A substrate; nilotinib is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Nimodipine: (Moderate) Monitor for decreased efficacy of nimodipine if coadministration with pexidartinib is necessary as concomitant use may decrease plasma concentrations of nimodipine. Nimodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of pexidartinib with ritonavir as concurrent use may increase exposure to pexidartinib and decrease exposure to ritonavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of ritonavir efficacy. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of pexidartinib is necessary. Concomitant use of nirmatrelvir and pexidartinib may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with pexidartinib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
    Nitrofurantoin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with nitrofurantoin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Nizatidine: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Non-oral combination contraceptives: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many non-oral combination contraceptives (injectable, transdermal, and implantable contraceptives) are metabolized by CYP3A.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Norethindrone: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Norethindrone; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Norgestimate; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Norgestrel: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Olaparib: (Major) Avoid coadministration of olaparib with pexidartinib due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A4 inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of paritaprevir with pexidartinib is contraindicated due to the potential for decreased paritaprevir concentrations and the potential development of viral resistance. Paritaprevir is metabolized by CYP3A4 and pexidartinib is a moderate CYP3A4 inducer. (Major) Avoid coadministration of pexidartinib with ombitasvir as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ombitasvir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ombitasvir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; ombitasvir is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%. (Major) Avoid coadministration of pexidartinib with ritonavir as concurrent use may increase exposure to pexidartinib and decrease exposure to ritonavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of ritonavir efficacy. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Omeprazole: (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Omeprazole; Sodium Bicarbonate: (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Oral Contraceptives: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of oxycodone as needed. If pexidartinib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Paclitaxel: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with pexidartinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Pantoprazole: (Major) Avoid coadministration of pexidartinib with pantoprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Peginterferon Alfa-2a: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with peginterferon alfa-2a. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Peginterferon Alfa-2b: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with peginterferon alfa-2b. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Peginterferon beta-1a: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with peginterferon beta-1a. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Pemigatinib: (Major) Avoid coadministration of pemigatinib and pexidartinib due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
    Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime if perampanel is added to pexidartinib therapy; increase the dose as tolerated in 2 mg increments no more than weekly, based on clinical response. If pexidartinib is added or withdrawn from perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Perampanel is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Perindopril; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Phenobarbital: (Major) Avoid coadministration of pexidartinib with phenobarbital as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of pexidartinib with phenobarbital as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Phenytoin: (Major) Avoid coadministration of pexidartinib with phenytoin as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and phenytoin may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Pimavanserin: (Major) Avoid coadministration of pimavanserin with pexidartinib as concurrent use may decrease pimavanserin exposure which may lead to decreased efficacy. Pimavanserin is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the exposure of pimavanserin by approximately 70%.
    Posaconazole: (Major) Avoid coadministration of pexidartinib with posaconazole as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If posaconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of posaconazole. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Praziquantel: (Moderate) Monitor for reduced response to praziquantel if coadministered with pexidartinib. Concomitant use may produce therapeutically ineffective concentrations of praziquantel. In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Pexidartinib is a moderate CYP3A4 inducer.
    Primidone: (Major) Avoid coadministration of pexidartinib with primidone as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Probenecid: (Major) Avoid coadministration of pexidartinib with probenecid as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If probenecid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of probenecid. Dose adjustments are as follows: 800 mg or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; probenecid is a UGT inhibitor. Coadministration with probenecid increased pexidartinib exposure by 60%.
    Probenecid; Colchicine: (Major) Avoid coadministration of pexidartinib with probenecid as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If probenecid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of probenecid. Dose adjustments are as follows: 800 mg or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; probenecid is a UGT inhibitor. Coadministration with probenecid increased pexidartinib exposure by 60%.
    Propylthiouracil, PTU: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with propylthiouracil. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Pyrazinamide, PZA: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with pyrazinamide. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Quinidine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with quinidine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Rabeprazole: (Major) Avoid coadministration of pexidartinib with rabeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
    Ranitidine: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
    Ranolazine: (Contraindicated) Coadministration of ranolazine with pexidartinib is contraindicated due to decreased ranolazine exposure and efficacy. Ranolazine is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the plasma concentrations of ranolazine by approximately 95%.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Ribociclib: (Major) Avoid coadministration of pexidartinib with ribociclib as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ribociclib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ribociclib. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Ribociclib; Letrozole: (Major) Avoid coadministration of pexidartinib with ribociclib as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If ribociclib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ribociclib. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Rifampin: (Major) Avoid coadministration of pexidartinib with rifampin as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and rifampin may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased pexidartinib exposure by 65%.
    Rifapentine: (Major) Avoid coadministration of pexidartinib with rifapentine as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Rilpivirine: (Moderate) Coadministration of rilpivirine with pexidartinib may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and pexidartinib. Discontinue riluzole if clinical signs of liver dysfunction are present. Concomitant use may increase the risk for hepatotoxicity.
    Rimegepant: (Major) Avoid coadministration of rimegepant with pexidartinib; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Ripretinib: (Major) Avoid coadministration of ripretinib with pexidartinib. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of pexidartinib. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and pexidartinib is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
    Ritonavir: (Major) Avoid coadministration of pexidartinib with ritonavir as concurrent use may increase exposure to pexidartinib and decrease exposure to ritonavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of ritonavir efficacy. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Saquinavir: (Major) Avoid coadministration of pexidartinib with saquinavir as concurrent use may increase exposure to pexidartinib and decrease exposure to saquinavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of saquinavir efficacy. If saquinavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of saquinavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and saquinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    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.
    Segesterone Acetate; Ethinyl Estradiol: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many non-oral combination contraceptives (injectable, transdermal, and implantable contraceptives) are metabolized by CYP3A. (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A.
    Selumetinib: (Major) Avoid coadministration of selumetinib and pexidartinib due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
    Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with pexidartinib is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
    Simvastatin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with simvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Simvastatin; Sitagliptin: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with simvastatin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Siponimod: (Moderate) Concomitant use of siponimod and pexidartinib is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
    Sirolimus: (Moderate) Monitor for loss of efficacy of sirolimus during coadministration of pexidartinib; a sirolimus dose adjustment may be necessary. Sirolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; pexidartinib is a moderate CYP3A4 inducer.
    Sofosbuvir; Velpatasvir: (Major) Concomitant use of velpatasvir with pexidartinib is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Concomitant use of velpatasvir with pexidartinib is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Solifenacin: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with pexidartinib is necessary. Solifenacin is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Sonidegib: (Major) Avoid the concomitant use of sonidegib and pexidartinib; sonidegib exposure may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A4 inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
    Sorafenib: (Major) Avoid coadministration of pexidartinib with sorafenib as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If sorafenib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of sorafenib. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; sorafenib is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of pexidartinib with St. John's Wort as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pexidartinib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of sufentanil injection as needed. If pexidartinib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Sulfadiazine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with sulfadiazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with sulfamethoxazole. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Sulfasalazine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with sulfasalazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Sulindac: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with sulindac. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate if coadministration with pexidartinib is necessary; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus concentrations. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; pexidartinib is a moderate CYP3A4 inducer.
    Tazemetostat: (Major) Avoid coadministration of tazemetostat with pexidartinib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Telithromycin: (Major) Avoid coadministration of pexidartinib with telithromycin as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If telithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of telithromycin. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Telmisartan; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with pexidartinib is necessary. Amlodipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
    Testosterone: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with testosterone. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Thioguanine, 6-TG: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with thioguanine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Ticlopidine: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ticlopidine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Tipranavir: (Major) Avoid coadministration of pexidartinib with tipranavir as concurrent use may increase exposure to pexidartinib and decrease exposure to tipranavir. If concurrent use cannot be avoided, reduce the dose of pexidartinib and monitor patients for a loss of tipranavir efficacy. If tipranavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of tipranavir. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Both drugs are CYP3A4 substrates. Additionally, pexidartinib is a moderate CYP3A4 inducer and tipranavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance.
    Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of tramadol as needed. If pexidartinib is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with pexidartinib is necessary; consider increasing the dose of tramadol as needed. If pexidartinib is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Trandolapril; Verapamil: (Major) Avoid coadministration of pexidartinib with verapamil as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If verapamil is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of verapamil. Pexidartinib is a CYP3A substrate; verapamil is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Tucatinib: (Major) Avoid coadministration of pexidartinib with tucatinib as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If tucatinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of tucatinib. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with pexidartinib as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
    Valproic Acid, Divalproex Sodium: (Major) Avoid coadministration of pexidartinib with valproic acid as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If valproic acid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of valproic acid. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a UGT substrate; valproic acid is a UGT inhibitor. Coadministration with another UGT inhibitor increased pexidartinib exposure by 60%.
    Venetoclax: (Major) Avoid coadministration of venetoclax with pexidartinib as concurrent use may decrease venetoclax exposure and lead to reduced efficacy. Venetoclax is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer decreased venetoclax exposure by 71%.
    Verapamil: (Major) Avoid coadministration of pexidartinib with verapamil as concurrent use may increase pexidartinib exposure and the risk of adverse events. If concurrent use cannot be avoided, reduce the dose of pexidartinib as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. If verapamil is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of verapamil. Pexidartinib is a CYP3A substrate; verapamil is a moderate CYP3A inhibitor. Based on modeling and simulation data, coadministration with another moderate CYP3A inhibitor was predicted to increase the pexidartinib exposure by 67%.
    Voclosporin: (Major) Avoid coadministration of voclosporin with pexidartinib. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
    Voriconazole: (Major) Avoid coadministration of pexidartinib with voriconazole as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If voriconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of voriconazole. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; voriconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Voxelotor: (Major) Avoid coadministration of voxelotor and pexidartinib as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,500 mg PO once daily. Voxelotor is a substrate of CYP3A4; pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease voxelotor exposure by up to 60%.
    Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with pexidartinib is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Pexidartinib is a CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
    Zanubrutinib: (Major) Avoid the concomitant use of zanubrutinib and pexidartinib. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. The AUC of zanubrutinib is predicted to decrease by 60% when coadministered with another moderate CYP3A4 inducer.

    PREGNANCY AND LACTATION

    Pregnancy

    Pexidartinib may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid becoming pregnant while receiving pexidartinib. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. In animal studies, embryo-fetal toxicities including localized fetal edema, absence of kidney and ureter, abnormalities of the reproductive tract, and developmental variations such as misshapen kidney, decreased skeletal ossification, and slightly or moderately malaligned sternebrae were observed in rats and absence of kidney or ureter, misshapen or malpositioned kidney, rib abnormalities, and skeletal variations of accessory skull bones were observed in rabbits at pexidartinib doses that resulted in maternal exposures that were about equal to the human exposure at the recommended dose of 800 mg.[64535]

    Counsel patients about the reproductive risk and contraception requirements during pexidartinib treatment. Pregnancy testing should be performed prior to starting pexidartinib in female patients of reproductive potential. These patients should use effective non-hormonal contraception and avoid pregnancy during and for 1 month after pexidartinib therapy. Concomitant use of pexidartinib and hormonal contraceptives may decrease the effectiveness of hormonal contraceptives. Women who become pregnant while receiving pexidartinib should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during and for 1 week after therapy due to the risk of male-mediated teratogenicity. Based on animal studies, pexidartinib may cause infertility in males and females.

    MECHANISM OF ACTION

    Pexidartinib is a selective tyrosine kinase inhibitor that blocks colony-stimulating factor-1 (CSF1) receptor, KIT, and FLT3. Tenosynovial giant cell tumor is a locally aggressive neoplasm of the joint or tendon sheath. The neoplastic cells typically express CSF1. Blocking CSF1 receptor inhibits cell proliferation and accumulation of tumor cells in the synovium. Pexidartinib inhibits the proliferation of cell lines dependent on CSF1 in vitro and in vivo.[64535] [64550]

    PHARMACOKINETICS

    Pexidartinib is administered orally. It is greater than 99% bound to plasma proteins (serum albumin, 99.9%; alfa-1 glycoprotein, 89.9%) and has an elimination half-life of 26.6 +/- 6.5 hours. Following a single 400-mg dose of pexidartinib in healthy volunteers, the apparent volume of distribution was 187 L (mean coefficient of variation (CV), 27%) and the apparent clearance was 5.1 L/hour (CV, 36%). Pexidartinib is metabolized in the liver by oxidation (via CYP3A4) and glucuronidation (via UGT1A4). The major inactive N-glucuronide metabolite is formed by UGT1A4 and has about a 10% higher exposure than pexidartinib following a single dose. Following a single dose of radiolabeled pexidartinib 400 mg, 65% of the dose was excreted in the feces (unchanged, 44%) and 27% of the dose was excreted as metabolites (N-glucuronide, 10% or greater).
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, UGT
    Pexidartinib is a substrate of CYP3A4 and UGT1A4; it is also a moderate CYP3A4 inducer. Avoid the concomitant use of pexidartinib with strong CYP3A4 inducers, moderate or strong CYP3A4 inhibitors, and UGT inhibitors; reduce the pexidartinib dosage if use with a moderate or strong CYP3A4 inhibitor or UGT inhibitor cannot be avoided. In vitro, pexidartinib is likely to inhibit CYP2B6 and UGT1A1 and induce CYP2B6 at clinically relevant concentrations; it may also inhibit MATE1, MATE2-K, OATP1B1, OATP1B3 and OATP2B1 transporters. No clinically relevant change in exposure was observed in drug interaction studies that evaluated the concomitant use of pexidartinib with a CYP2C19 substrate (omeprazole AUC decreased by 17%), a CYP2C9 substrate (tolbutamide), or a P-glycoprotein substrate (digoxin AUC increased by 9%). No interaction is predicted with concomitant use of a CYP2C8 substrate based on modeling and simulation data.[64535]

    Oral Route

    Following multiple oral doses of pexidartinib 400 mg twice daily, the mean AUC(0-12h) and Cmax values were 77,465 (+/- 24,975) ng/mL x hour and 8,625 (+/- 2,746) ng/mL, respectively. The median time to maximum plasma concentration (Tmax) was 2.5 hours post-dose; the estimated time to steady-state concentrations was 7 days. The pexidartinib AUC(0-inf) and Cmax values increased linearly over the single oral dose range of 200 to 2,400 mg; the median AUC accumulation ratio was 3.6.
    Effects of food: Due to the risk of hepatotoxicity with increased exposure, pexidartinib should be taken on an empty stomach. When pexidartinib was administered with a high-fat meal (800 to 1,000 calories with about 50% of the total caloric content consisting of fat), AUC(0-inf) and Cmax values were increased by 100% and the Tmax was delayed by 2.5 hours compared with the fasted state. When pexidartinib was administered with a low-fat meal (387 calories with about 25% of the total caloric content consisting of fat), the AUC(0-inf) value was increased by 59%, the Cmax was increased by 56%, and the Tmax was delayed by 1.5 hours compared with the fasted state.[64535]