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Drug Interactions between atazanavir / cobicistat and dronedarone

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

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Interactions between your drugs

Major

atazanavir dronedarone

Applies to: atazanavir / cobicistat and dronedarone

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of dronedarone, which is primarily metabolized by the isoenzyme. According to the product labeling for dronedarone, administration of repeated doses of the potent inhibitor ketoconazole led to a 9-fold increase in dronedarone peak plasma concentration (Cmax) and a 17-fold increase in systemic exposure (AUC). 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.

MANAGEMENT: The use of dronedarone in combination with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, cyclosporine, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics is considered contraindicated. Patients currently receiving these agents should stop taking them before starting treatment with dronedarone. Some authorities consider concomitant administration of dronedarone and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2009) "Product Information. Multaq (dronedarone)." sanofi-aventis

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Major

dronedarone cobicistat

Applies to: dronedarone and atazanavir / cobicistat

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of dronedarone, which is primarily metabolized by the isoenzyme. According to the product labeling for dronedarone, administration of repeated doses of the potent inhibitor ketoconazole led to a 9-fold increase in dronedarone peak plasma concentration (Cmax) and a 17-fold increase in systemic exposure (AUC). 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.

MANAGEMENT: The use of dronedarone in combination with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, cyclosporine, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics is considered contraindicated. Patients currently receiving these agents should stop taking them before starting treatment with dronedarone. Some authorities consider concomitant administration of dronedarone and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2009) "Product Information. Multaq (dronedarone)." sanofi-aventis

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Drug and food interactions

Major

dronedarone food

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

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Moderate

atazanavir food

Applies to: atazanavir / cobicistat

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb

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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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