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Drug Interactions between Biaxin XL and pexidartinib

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

clarithromycin pexidartinib

Applies to: Biaxin XL (clarithromycin) and pexidartinib

GENERALLY AVOID: Coadministration of pexidartinib with strong CYP450 3A4 inhibitors and/or uridine diphosphate glucuronosyltransferase (UGT) inhibitors may significantly increase the plasma concentrations and the incidence and severity of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The proposed mechanism is inhibition of CYP450 3A4 and/or UGT, the primary isoenzymes responsible for the metabolic clearance of pexidartinib. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively. Coadministration with probenecid, a UGT inhibitor, increased pexidartinib Cmax and AUC by 5% and 60%, respectively.

MANAGEMENT: The use of pexidartinib with strong CYP450 3A4 inhibitors and/or UGT inhibitors should generally be avoided. If concomitant use is required, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of a strong CYP450 3A4 inhibitor or UGT inhibitor is discontinued, the dose of pexidartinib may be increased, after 3 plasma half-lives of the strong CYP450 3A4 inhibitor or UGT inhibitor, to the dose that was used prior to starting the strong CYP450 3A4 inhibitor or UGT inhibitor.

References

  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.

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Drug and food interactions

Major

pexidartinib food

Applies to: pexidartinib

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of pexidartinib. Administration of pexidartinib with a high-fat meal increased peak plasma concentration (Cmax) and systemic exposure (AUC) by 100% and prolonged the time to reach peak plasma concentration (Tmax) by 2.5 hours.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentration and risk of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The mechanism is inhibition of CYP450 3A4-mediated metabolism of pexidartinib by certain compounds present in grapefruits. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively.

MANAGEMENT: Pexidartinib should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. Consumption of grapefruit or grapefruit juice should generally be avoided during pexidartinib therapy. If concomitant use is unavoidable, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of grapefruit or grapefruit juice is discontinued, the dose of pexidartinib may be increased (after 3 plasma half-lives of a strong CYP450 3A4 inhibitor) to the dose that was used prior to consumption of grapefruit or grapefruit juice.

References

  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.

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Minor

clarithromycin food

Applies to: Biaxin XL (clarithromycin)

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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