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Drug Interactions between Multaq and nintedanib

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

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Interactions between your drugs

Moderate

dronedarone nintedanib

Applies to: Multaq (dronedarone) and nintedanib

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and CYP450 3A4 may increase the plasma concentrations of nintedanib, which is a substrate of the efflux transporter and a minor substrate of the isoenzyme. In a dedicated drug interaction study, administration of nintedanib with the potent P-gp and CYP450 3A4 inhibitor, ketoconazole, increased nintedanib peak plasma concentration (Cmax) by 83% and systemic exposure (AUC) by 61%. No data are available for use with other, less potent inhibitors.

MANAGEMENT: Caution is advised if nintedanib is prescribed in combination with P-gp and CYP450 3A4 inhibitors. Pharmacologic response to nintedanib should be monitored more closely whenever a CYP450 3A4/P-gp inhibitor is added to or withdrawn from therapy, and the nintedanib dosing adjusted or interrupted as necessary in accordance with the product labeling. Patients should be closely monitored for increased adverse effects such as liver enzyme and bilirubin elevations, diarrhea, nausea, vomiting, gastrointestinal perforation, bleeding, and arterial thromboembolic events (e.g., myocardial infarction).

References

  1. "Product Information. Ofev (nintedanib)." Boehringer Ingelheim (2014):

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Drug and food interactions

Major

dronedarone food

Applies to: Multaq (dronedarone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of dronedarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration with grapefruit juice resulted in a 2.5-fold increase in dronedarone peak plasma concentration and a 3-fold increase in systemic exposure. Because dronedarone 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.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of dronedarone. The mechanism of interaction is unknown. According to the product labeling, the absolute bioavailability of dronedarone increases from about 4% when administered in the fasted state to approximately 15% when administered with a high-fat meal.

MANAGEMENT: Patients treated with dronedarone should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Dronedarone should be taken twice daily with the morning and evening meals.

References

  1. "Product Information. Multaq (dronedarone)." sanofi-aventis (2009):

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Moderate

nintedanib food

Applies to: nintedanib

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of nintedanib. After food intake, nintedanib exposure increased by approximately 20% compared to administration under fasted conditions. Absorption was also delayed, as indicated by an increase in the median time to reach maximum plasma concentration (Tmax) from 2 hours in the fasted state to approximately 4 hours under fed conditions, irrespective of the type of food ingested.

MANAGEMENT: Nintedanib should be administered with food.

References

  1. "Product Information. Ofev (nintedanib)." Boehringer Ingelheim (2014):

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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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