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Drug Interactions between crizotinib and mitoxantrone

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

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Interactions between your drugs

Moderate

mitoXANTRONE crizotinib

Applies to: mitoxantrone and crizotinib

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of mitoxantrone, which is a substrate of the efflux transporter also known as ABCB1 or MDR1. The interaction has been studied with cyclosporine, a potent P-gp inhibitor. In a pharmacokinetic study of 38 children with de novo acute myeloid leukemia, mitoxantrone 6 mg/m2 administered daily in combination with cyclosporine resulted in a 42% decrease in mean mitoxantrone clearance and 12% increase in systemic exposure (AUC) compared to mitoxantrone 10 mg/m2 administered daily without cyclosporine. There were no differences in the rates of stomatitis or infection between the two groups, but an increased incidence of hyperbilirubinemia was observed in the cyclosporine group, which rapidly reversed upon conclusion of treatment. Therefore, it appears a 40% dose reduction of mitoxantrone given with cyclosporine produced statistically similar systemic exposure and toxicity as mitoxantrone given alone.

MANAGEMENT: Caution is advised if mitoxantrone is prescribed in combination with a P-gp inhibitor. Patients should be closely monitored for increased adverse effects including cardiotoxicity and myelosuppression.

References (2)
  1. "Multum Information Services, Inc. Expert Review Panel"
  2. (2001) "Product Information. Novantrone (mitoxantrone)." Immunex Corporation

Drug and food interactions

Major

crizotinib food

Applies to: crizotinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.

References (1)
  1. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group

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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