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Drug Interactions between Gilotrif and Xalkori

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

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Interactions between your drugs

Moderate

crizotinib afatinib

Applies to: Xalkori (crizotinib) and Gilotrif (afatinib)

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of afatinib, which is a substrate of the efflux transporter. In study subjects, oral administration of the P-gp inhibitor ritonavir (200 mg twice daily) one hour before afatinib dosing resulted in a 48% increase in afatinib systemic exposure. There was no change in afatinib exposure when ritonavir was administered simultaneously with, or 6 hours after, the afatinib dose.

MANAGEMENT: Caution is advised if afatinib is used in combination with P-gp inhibitors. Patients should be monitored for potentially increased adverse effects such as diarrhea, which may lead to dehydration with or without renal impairment; cutaneous reactions including rash, erythema, and bullous, blistering, or exfoliating lesions; interstitial lung disease such as lung infiltration, pneumonitis, acute respiratory distress syndrome, and allergic alveolitis; hepatotoxicity, which may be life-threatening or fatal; keratitis characterized by acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye, and/or ulceration; and left ventricular dysfunction. The manufacturer recommends reducing the daily dose of afatinib by 10 mg if not tolerated. The previous dose may be resumed after discontinuation of the P-gp inhibitor as tolerated.

References

  1. "Product Information. Gilotrif (afatinib)." Boehringer Ingelheim (2013):

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Drug and food interactions

Major

crizotinib food

Applies to: Xalkori (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. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

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Moderate

afatinib food

Applies to: Gilotrif (afatinib)

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of afatinib. According to the product labeling, administration of afatinib with a high-fat meal decreased peak plasma concentration (Cmax) by 50% and systemic exposure (AUC) by 39% compared to administration in the fasted state.

MANAGEMENT: Afatinib should be taken at least 1 hour before or 2 hours after a meal.

References

  1. "Product Information. Gilotrif (afatinib)." Boehringer Ingelheim (2013):

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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

Multikinase inhibitors

Therapeutic duplication

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

  • Gilotrif (afatinib)
  • Xalkori (crizotinib)

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.

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