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Drug Interactions between daclatasvir and pexidartinib

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

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Interactions between your drugs

Major

daclatasvir pexidartinib

Applies to: daclatasvir and pexidartinib

ADJUST DOSE: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of daclatasvir, which is primarily metabolized by the isoenzyme. In 17 healthy volunteers, administration of daclatasvir 120 mg daily for 4 days during concomitant treatment with the moderate CYP450 3A4 inducer efavirenz (600 mg once daily for 14 days) decreased daclatasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 33%, 63% and 17%, respectively, compared to administration of daclatasvir alone at 60 mg daily for 4 days. Linear dose scaling predicted that an increase in the daclatasvir dosage to 90 mg daily when used with efavirenz or other moderate CYP450 3A4 inducers would result in an AUC comparable to that produced by daclatasvir alone at 60 mg daily.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, an increase in the dosage of daclatasvir to 90 mg once daily is recommended when used with moderate CYP450 3A4 inducers.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2015) "Product Information. Daklinza (daclatasvir)." Bristol-Myers Squibb

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

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.

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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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