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Drug Interactions between pexidartinib and Prograf

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

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Interactions between your drugs

Moderate

tacrolimus pexidartinib

Applies to: Prograf (tacrolimus) and pexidartinib

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of sirolimus and tacrolimus, both of which are primarily metabolized by the isoenzyme.

MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant drug levels, caution is advised during concomitant therapy with CYP450 3A4 inducers. Sirolimus and tacrolimus blood levels should be checked frequently and the dosage adjusted accordingly whenever a CYP450 3A4 inducer is added to or withdrawn from therapy.

References

  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. (2001) "Product Information. Rapamune (sirolimus)." Wyeth-Ayerst Laboratories
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 references

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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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Moderate

tacrolimus food

Applies to: Prograf (tacrolimus)

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References

  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11

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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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