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Drug Interactions between axitinib and pazopanib

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

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Interactions between your drugs

Moderate

PAZOPanib axitinib

Applies to: pazopanib and axitinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of axitinib, which is primarily metabolized by the isoenzyme. In 32 healthy volunteers, administration of a single 5 mg dose of axitinib on day 4 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 7 days) resulted in a 1.5-fold increase in mean axitinib peak plasma concentration (Cmax) and 2-fold increase in mean systemic exposure (AUC) compared to administration of axitinib alone. The mean plasma half-life of axitinib also increased from 9.4 hours when given alone to 13.1 hours in the presence of ketoconazole. The combination was well tolerated by study subjects. Most treatment-related adverse events were mild in severity, with headache and nausea reported most frequently. No clinically significant effects on blood pressure were observed for single-dose axitinib plus ketoconazole relative to axitinib alone.

MANAGEMENT: Caution is advised if axitinib is prescribed with CYP450 3A4 inhibitors. Alternative agents with no or minimal CYP450 3A4 inhibition potential are recommended whenever possible. Otherwise, patients should be monitored closely for development of toxicity such as hypertension/hypertensive crisis, arterial and venous thromboembolic complications, hemorrhage, gastrointestinal perforation or fistula, thyroid dysfunction, reversible posterior leukoencephalopathy syndrome, proteinuria, and liver enzyme elevations or hepatic impairment.

References

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

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Drug and food interactions

Major

PAZOPanib food

Applies to: pazopanib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.

References

  1. (2009) "Product Information. Votrient (pazopanib)." GlaxoSmithKline

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Moderate

axitinib food

Applies to: axitinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.

References

  1. (2012) "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Vegf/vegfr inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'VEGF/VEGFR inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'VEGF/VEGFR inhibitors' category:

  • axitinib
  • pazopanib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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.

Medical Disclaimer