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Drug Interactions between bosutinib and ranolazine

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

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Interactions between your drugs

Moderate

ranolazine bosutinib

Applies to: ranolazine and bosutinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of bosutinib, which is a substrate of the isoenzyme and efflux transporter. In 24 healthy volunteers, administration of a single 100 mg dose of bosutinib with the potent CYP450 3A4 and P-gp inhibitor ketoconazole (400 mg/day for 5 days) under fasting conditions resulted in a 5.2-fold increase in bosutinib peak plasma concentration (Cmax) and 8.6-fold increase in systemic exposure (AUC) compared to administration of bosutinib alone. Ketoconazole also decreased the mean apparent clearance of bosutinib by approximately 9-fold and increased the mean terminal half-life from 46.2 hours to 69.0 hours. No data are available for use with less potent CYP450 3A4 inhibitors or P-gp inhibitors.

MANAGEMENT: Caution is advised when bosutinib is used with CYP450 3A4 or P-gp inhibitors. Patients should be monitored more closely for development of adverse effects such as diarrhea, nausea, vomiting, abdominal pain, myelosuppression, hepatotoxicity, and fluid retention (e.g., pericardial effusion, pleural effusion, pulmonary edema, peripheral edema).

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2012) "Product Information. Bosulif (bosutinib)." Pfizer U.S. Pharmaceuticals Group

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Drug and food interactions

Major

ranolazine food

Applies to: ranolazine

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.

MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.

References

  1. (2006) "Product Information. Ranexa (ranolazine)." Calmoseptine Inc

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Moderate

bosutinib food

Applies to: bosutinib

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bosutinib. When given with a high-fat meal, bosutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.8- and 1.7-fold, respectively.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of bosutinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Bosutinib should be administered with a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.

References

  1. (2012) "Product Information. Bosulif (bosutinib)." Pfizer U.S. Pharmaceuticals Group

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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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