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Drug Interactions between Cardura and pexidartinib

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

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Interactions between your drugs

Moderate

doxazosin pexidartinib

Applies to: Cardura (doxazosin) and pexidartinib

GENERALLY AVOID: Coadministration with pexidartinib may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is increased clearance due to pexidartinib-mediated induction of CYP450 3A4 isoenzyme. Coadministration with pexidartinib (400 mg twice daily) decreased the total systemic exposure (AUC 0-INF) and peak plasma concentration (Cmax) of midazolam (a sensitive CYP450 3A4 substrate) by 59% and 28%, respectively.

MANAGEMENT: Concomitant administration of pexidartinib with drugs that are substrates of CYP450 3A4 should generally be avoided, particularly those with a narrow therapeutic range. The potential for diminished therapeutic effects should be considered when pexidartinib is prescribed in combination with drugs that are substrates of CYP450 3A4. Dosage adjustments as well as clinical and laboratory monitoring of the CYP450 3A4 substrate drug should be considered whenever pexidartinib is added to or withdrawn from therapy with these drugs.

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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Moderate

doxazosin food

Applies to: Cardura (doxazosin)

GENERALLY AVOID: The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects. Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction. The mechanism has not been determined. Data exist for prazosin and other alpha adrenergic blockers are expected to interact also. In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

MANAGEMENT: Patients who develop a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake. All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

References

  1. Kawano Y, Abe H, Kojima S, Takishita S, Omae T (2000) "Interaction of alcohol and an a1-blocker on ambulatory blood pressure in patients with essential hypertension." Am J Hypertens, 13, p. 307-12
  2. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc

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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.


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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.