Turalio

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

Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.

Oral Administration Oral Solid Formulations

Take pexidartinib with a low-fat meal (approximately 11 to 14 g of total fat).
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 receptor 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]

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

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 (LFTs) 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, administer pexidartinib with a low-fat meal (approximately 11 to 14 g of total fat). Avoid taking pexidartinib with a high-fat meal (approximately 55 to 65 g of total fat) because pexidartinib levels may increase 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]

Turalio

Rx

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

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

250 mg orally twice daily 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. Safety and efficacy have been established for the pexidartinib 250 mg orally twice daily dosage administered with a low-fat meal based on adequate and well-controlled studies in patients who received the 400 mg PO twice daily dosage on an empty stomach and pharmacokinetic data that showed no clinically significant differences in relative exposure between the 2 dosage regimens. The overall response rate (ORR) at 25 weeks was 39% in patients with advanced tenosynovial giant cell tumor (TGCT) who received pexidartinib (n = 61) compared with 0% of patients who received placebo (n = 59; p less than 0.0001) in a multinational, randomized, double-blind, phase 3 (ENLIVEN) trial. The ORR was 61% in patients originally assigned to the pexidartinib arm in the randomized trial and who continued on pexidartinib in an open-label extension study; the median duration of response was not reached (range, 4.6 to more than 63.4 months) in responding patients. 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]

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: 125 mg PO in the morning and 250 mg PO in the evening.Second dose reduction: 125 mg PO twice daily; permanently discontinue therapy in patients unable to tolerate 250 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 125 mg PO in the morning and 250 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]

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; 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.
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.
Adagrasib: (Major) Avoid concomitant use of pexidartinib and adagrasib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If adagrasib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of adagrasib. Pexidartinib is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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.
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 concomitant use of pexidartinib and amiodarone due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease amiodarone plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If amiodarone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of amiodarone. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary and 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 and moderate CYP3A inducer, amiodarone is a CYP3A substrate and moderate CYP3A inhibitor, and both medications have been associated with hepatotoxicity. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 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%. (Major) Avoid concomitant use of pexidartinib and clarithromycin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease clarithromycin plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; clarithromycin is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
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 concomitant use of pexidartinib and aprepitant/fosaprepitant due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If aprepitant/fosaprepitant is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of aprepitant/fosaprepitant. Pexidartinib is a CYP3A substrate; aprepitant/fosaprepitant is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
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 concomitant use of pexidartinib and atazanavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease atazanavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If atazanavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of atazanavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; atazanavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of pexidartinib and atazanavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease atazanavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If atazanavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of atazanavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; atazanavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. (Major) Avoid concomitant use of pexidartinib and cobicistat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cobicistat plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; cobicistat is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Atogepant: (Major) Avoid use of atogepant and pexidartinib when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine 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.
Berotralstat: (Major) Avoid concomitant use of pexidartinib and berotralstat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If berotralstat is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of berotralstat. Pexidartinib is a CYP3A substrate; berotralstat is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
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.
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.
Butalbital; Aspirin; 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 concomitant use of pexidartinib and cannabidiol due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If cannabidiol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cannabidiol. Pexidartinib is a UGT substrate; cannabidiol is a UGT inhibitor. Coadministration of 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%.
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.
Celecoxib; 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.
Ceritinib: (Major) Avoid concomitant use of pexidartinib and ceritinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ceritinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ceritinib. Pexidartinib is a CYP3A substrate; ceritinib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Chloramphenicol: (Major) Avoid concomitant use of pexidartinib and chloramphenicol due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If chloramphenicol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of chloramphenicol. Pexidartinib is a CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor. Coadministration of another strong CYP3A 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; 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; 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 concomitant use of pexidartinib and ciprofloxacin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Clarithromycin: (Major) Avoid concomitant use of pexidartinib and clarithromycin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease clarithromycin plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; clarithromycin is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
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 concomitant use of pexidartinib and cobicistat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cobicistat plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; cobicistat is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A 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 concomitant use of pexidartinib and conivaptan due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If conivaptan is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of conivaptan. Pexidartinib is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Crizotinib: (Major) Avoid concomitant use of pexidartinib and crizotinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Cyclosporine: (Major) Avoid concomitant use of pexidartinib and cyclosporine due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cyclosporine plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; cyclosporine is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 concomitant use of pexidartinib and danazol due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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).
Daridorexant: (Major) Avoid concomitant use of daridorexant and pexidartinib. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
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 CYP3A inducer and darifenacin is a CYP3A substrate; coadministration may result in decreased plasma concentrations of darifenacin.
Darunavir: (Major) Avoid concomitant use of pexidartinib and darunavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease darunavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; darunavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Darunavir; Cobicistat: (Major) Avoid concomitant use of pexidartinib and cobicistat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cobicistat plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; cobicistat is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. (Major) Avoid concomitant use of pexidartinib and darunavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease darunavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; darunavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of pexidartinib and cobicistat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cobicistat plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; cobicistat is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. (Major) Avoid concomitant use of pexidartinib and darunavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease darunavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; darunavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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 concomitant use of pexidartinib and delavirdine due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease delavirdine plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; delavirdine is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Coadministration with another moderate CYP3A inducer decreased delavirdine exposure by 82%.
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.
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.
Diltiazem: (Major) Avoid concomitant use of pexidartinib and diltiazem due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease diltiazem plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. Monitor blood pressure and heart rate and adjust the diltiazem dose based on clinical response. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; diltiazem is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%. Coadministration with another moderate CYP3A inducer decreased diltiazem exposure by 69%.
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 concomitant use of pexidartinib and dronedarone due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 co

ntraceptives 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 pexidartinib and duvelisib due to the risk of increased pexidartinib exposure and decreased duvelisib exposure. If concomitant use is necessary, the dose of both drugs will need to be adjusted. Dose adjustments for pexidartinib are as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. For duvelisib, 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. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; duvelisib is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
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 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.
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.
Elacestrant: (Major) Avoid concurrent use of elacestrant and pexidartinib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
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; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of pexidartinib and cobicistat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cobicistat plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; cobicistat is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A 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 concomitant use of pexidartinib and cobicistat due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease cobicistat plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A substrate and moderate CYP3A inducer; cobicistat is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A 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 concomitant use of pexidartinib and erlotinib due to the risk of increased pexidartinib exposure and decreased erlotinib exposure. If concomitant use is necessary, the dose of both drugs will need to be adjusted. Dose adjustments for pexidartinib are as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. For erlotinib, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Pexidartinib is a UGT substrate and moderate CYP3A inducer; erlotinib is a CYP3A substrate and UGT inhibitor. Coadministration of another UGT inhibitor increased pexidartinib exposure by 60%.
Erythromycin: (Major) Avoid concomitant use of pexidartinib and erythromycin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If erythromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of erythromycin. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary and 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 and erythromycin is a moderate CYP3A inhibitor, and both medications have been associated with hepatotoxicity. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
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; 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%.
Fedratinib: (Major) Avoid concomitant use of pexidartinib and fedratinib due to the risk of increased pexidartinib exposure and decreased fedratinib exposure. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If fedratinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of fedratinib. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; fedratinib is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%. Coadministration of fedratinib with another moderate CYP3A inducer decreased the overall exposure of fedratinib by 47%.
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 concomitant use of pexidartinib and fluconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of fluconazole is predicted to increase the pexidartinib overall 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 concomitant use of pexidartinib and fluvoxamine due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Fosamprenavir: (Major) Avoid concomitant use of pexidartinib and fosamprenavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease fosamprenavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If fosamprenavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of fosamprenavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
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%.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and pexidartinib due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
Gemfibrozil: (Major) Avoid concomitant use of pexidartinib and gemfibrozil due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If gemfibrozil is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of gemfibrozil. Pexidartinib is a UGT substrate; gemfibrozil is a UGT inhibitor. Coadministration of another UGT inhibitor increased pexidartinib exposure by 60%.
Glecaprevir; Pibrentasvir: (Major) Avoid concomitant use of pexidartinib and glecaprevir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease glecaprevir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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 CYP3A inducer; glecaprevir is a CYP3A substrate and UGT inhibitor. Coadministration of another UGT inhibitor increased pexidartinib exposure by 60%. (Major) Avoid concomitant use of pexidartinib and pibrentasvir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If pibrentasvir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of pibrentasvir. Pexidartinib is a UGT substrate; pibrentasvir is a UGT inhibitor. Coadministration of another UGT inhibitor increased pexidartinib exposure by 60%.
Grapefruit juice: (Major) Advise patients to avoid grapefruit or grapefruit juice during pexidartinib treatment due to the risk of increased pexidartinib exposure and adverse reactions. Pexidartinib is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
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.
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; 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; 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; 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%. (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 concomitant use of pexidartinib and idelalisib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If idelalisib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of idelalisib. Pexidartinib is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A 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 concomitant use of pexidartinib and imatinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Indinavir: (Major) Avoid concomitant use of pexidartinib and indinavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease indinavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If indinavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of indinavir. 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 CYP3A inducers. Pexidartinib is a CYP3A and UGT substrate and moderate CYP3A inducer; indinavir is a CYP3A substrate, strong CYP3A inhibitor, and UGT inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Coadministration with another moderate CYP3A inducer decreased indinavir exposure by up to 46%.
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-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-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 concomitant use of pexidartinib and isavuconazonium due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 concomitant use of pexidartinib and itraconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If itraconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of itraconazole. Pexidartinib is a CYP3A substrate; itraconazole is a strong CYP3A inhibitor. Coadministration with itraconazole increased pexidartinib exposure by 70%.
Ketoconazole: (Major) Avoid concomitant use of pexidartinib and ketoconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. 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 and 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 and ketoconazole is a strong CYP3A inhibitor, and both medications have been associated with hepatotoxicity. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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 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%. (Major) Avoid concomitant use of pexidartinib and clarithromycin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease clarithromycin plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; clarithromycin is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and pexidartinib due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If pexidartinib is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of pexidartinib. Larotrectinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid concomitant use of pexidartinib and lefamulin due to the risk of increased pexidartinib exposure and decreased lefamulin exposure. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If lefamulin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of lefamulin. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; lefamulin is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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.
Lenacapavir: (Major) Avoid concomitant use of pexidartinib and lenacapavir due to the risk of increased pexidartinib exposure and decreased lenacapavir exposure. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If lenacapavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of lenacapavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; lenacapavir is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and pexidartinib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
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 concomitant use of pexidartinib and letermovir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 concomitant use of pexidartinib and ketoconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. 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 and 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 and ketoconazole is a strong CYP3A inhibitor, and both medications have been associated with hepatotoxicity. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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.
Levonorgestrel; 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.
Lonafarnib: (Contraindicated) Concurrent use of lonafarnib and pexidartinib is contraindicated due to the risk of decreased lonafarnib exposure which may reduce its efficacy. Concomitant use may also increase pexidartinib exposure and the risk for pexidartinib-related adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If lonafarnib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of lonafarnib. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; lonafarnib is a sensitive CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of pexidartinib and ritonavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease ritonavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Pexidartinib is a CYP3A and substrate and moderate CYP3A inducer; ritonavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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.
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.
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.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with pexidartinib due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and pexidartinib is a moderate CYP3A 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.
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 concomitant use of pexidartinib and mifepristone due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If mifepristone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of mifepristone. Pexidartinib is a CYP3A substrate; mifepristone is a strong CYP3A inhibitor. Coadministration of another strong CYP3A 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.
Mitapivat: (Major) Avoid coadministration of mitapivat with pexidartinib, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
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: (Mode rate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with pexidartinib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and pexidartinib is a moderate CYP3A 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 concomitant use of pexidartinib and nefazodone due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If nefazodone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of nefazodone. Pexidartinib is a CYP3A substrate; nefazodone is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Nelfinavir: (Major) Avoid concomitant use of pexidartinib and nelfinavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease nelfinavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If nelfinavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of nelfinavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; nelfinavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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 concomitant use of pexidartinib and netupitant due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 concomitant use of pexidartinib and nilotinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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 concomitant use of pexidartinib and ritonavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease ritonavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Pexidartinib is a CYP3A and substrate and moderate CYP3A inducer; ritonavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. (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.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and pexidartinib due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and pexidartinib. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
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.
Pacritinib: (Major) Avoid concurrent use of pacritinib with pexidartinib due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and pexidartinib. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and pexidartinib is a moderate CYP3A 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%.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and pexidartinib due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. If concomitant use is necessary, an empiric pirtobrutinib dosage increase is required. If the current dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Pirtobrutinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%.
Posaconazole: (Major) Avoid concomitant use of pexidartinib and posaconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If posaconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of posaconazole. Pexidartinib is a CYP3A substrate; posaconazole is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Pralsetinib: (Major) Avoid concurrent use of pexidartinib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Pretomanid: (Major) Avoid coadministration of pretomanid with pexidartinib as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Concurrent use may also increase the risk of hepatotoxicity. Pretomanid is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
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 concomitant use of pexidartinib and probenecid due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If probenecid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of probenecid. Pexidartinib is a UGT substrate; probenecid is a UGT inhibitor. Coadministration of probenecid increased pexidartinib exposure by 60%.
Probenecid; Colchicine: (Major) Avoid concomitant use of pexidartinib and probenecid due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If probenecid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of probenecid. Pexidartinib is a UGT substrate; probenecid is a UGT inhibitor. Coadministration of 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.
Quizartinib: (Major) Avoid concomitant use of pexidartinib with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
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 concomitant use of pexidartinib and ribociclib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ribociclib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ribociclib. Pexidartinib is a CYP3A substrate; ribociclib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Ribociclib; Letrozole: (Major) Avoid concomitant use of pexidartinib and ribociclib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ribociclib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ribociclib. Pexidartinib is a CYP3A substrate; ribociclib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A 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%.
Ritlecitinib: (Major) Avoid concomitant use of pexidartinib and ritlecitinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ritlecitinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritlecitinib. Pexidartinib is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Ritonavir: (Major) Avoid concomitant use of pexidartinib and ritonavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease ritonavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ritonavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ritonavir. Pexidartinib is a CYP3A and substrate and moderate CYP3A inducer; ritonavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Saquinavir: (Major) Avoid concomitant use of pexidartinib and saquinavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease saquinavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If saquinavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of saquinavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; saquinavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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.
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 sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of pexidartinib. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and pexidartinib is a moderate CYP3A 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 concomitant use of pexidartinib and sorafenib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If sorafenib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of sorafenib. Pexidartinib is a UGT substrate; sorafenib is a UGT inhibitor. Coadministration of 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.
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 concomitant use of pexidartinib and tipranavir due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease tipranavir plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If tipranavir is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of tipranavir. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; tipranavir is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
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 concomitant use of pexidartinib and verapamil due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Tucatinib: (Major) Avoid concomitant use of pexidartinib and tucatinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If tucatinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of tucatinib. Pexidartinib is a CYP3A substrate; tucatinib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A 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 concomitant use of pexidartinib and valproic acid due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. 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 and 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 UGT substrate and valproic acid is a UGT inhibitor, and both medications have been associated with hepatotoxicity. Coadministration of 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 concomitant use of pexidartinib and verapamil due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 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. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall 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%.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and pexidartinib due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Additionally, vonoprazan reduces intragastric acidity, which may decrease the absorption of pexidartinib reducing its efficacy. Vonoprazan is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of pexidartinib and clarithromycin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease clarithromycin plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If clarithromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of clarithromycin. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; clarithromycin is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. (Major) Avoid concomitant use of vonoprazan and pexidartinib due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Additionally, vonoprazan reduces intragastric acidity, which may decrease the absorption of pexidartinib reducing its efficacy. Vonoprazan is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Voriconazole: (Major) Avoid concomitant use of pexidartinib and voriconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects; concomitant use may also decrease voriconazole plasma concentrations and reduce its efficacy. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If voriconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of voriconazole. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; voriconazole is a CYP3A substrate and strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%. Coadministration with another moderate CYP3A inducer decreased voriconazole exposure by 77%.
Voxelotor: (Major) Avoid concomitant use of pexidartinib and voxelotor due to the risk of increased pexidartinib exposure and decreased voxelotor exposure. If concomitant use is necessary, the dose of both drugs will need to be adjusted. Dose adjustments for pexidartinib are as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. For voxelotor, increase dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments for voxelotor are recommended; consult product labeling for specific recommendations. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; voxelotor is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
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 concurrent use of zanubrutinib and pexidartinib due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if pexidartinib is discontinued. Zanubrutinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.

Pexidartinib/Turalio Oral Cap: 125mg, 200mg

Adults

500 mg/day PO.

Geriatric

500 mg/day PO.

Adolescents

Safety and efficacy not established.

Children

Safety and efficacy not established.

Infants

Safety and efficacy not established.

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]

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 (on an empty stomach) 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. In vitro, pexidartinib inhibited CYP2B6 and UGT1A1 and induced CYP2B6 at clinically relevant concentrations; pexidartinib also inhibited 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), a CYP2C9 substrate (tolbutamide), a P-glycoprotein substrate (digoxin), or a CYP2C8 substrate.[64535]

Oral Route

Following multiple oral doses of pexidartinib 400 mg twice daily (on an empty stomach), the mean steady-state 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 (on an empty stomach) range of 200 to 2,400 mg; the median AUC accumulation ratio was 3.6.
Effects of food: When a pexidartinib dose of 400 mg was administered with a high-fat meal (800 to 1,000 calories with about 50% from fat [55 to 65 g]), AUC(0-inf) and Cmax values were increased by 100% and the Tmax was delayed by 2.5 hours compared with the fasted state. However, there was no clinically significant difference in the predicted relative AUC(0-24h) value when a pexidartinib dose of 250 mg was given with a low-fat meal (about 400 calories with about 25% from fat [11 to 14 g]) compared with a pexidartinib dose of 400 mg given on an empty stomach.[64535]

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.