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Drug Interactions between dronedarone and Triumeq PD

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

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Interactions between your drugs

Minor

dronedarone dolutegravir

Applies to: dronedarone and Triumeq PD (abacavir / dolutegravir / lamivudine)

Theoretically, coadministration with inhibitors of UGT1A or CYP450 3A4 isoenzymes may increase the plasma concentrations of dolutegravir, which is primarily metabolized by UGT1A1 with some contribution from CYP450 3A4. Dolutegravir is also a substrate of UGT1A3, UGT1A9, and P-glycoprotein in vitro. Potent CYP450 3A4 inhibitors such as boceprevir (800 mg every 8 hours) and telaprevir (750 mg every 8 hours) had no significant effects on the pharmacokinetics of dolutegravir given at 50 mg once daily. The interaction has not been studied or reported with UGT1A1 inhibitors such as nilotinib, regorafenib, and sorafenib. However, it is possible that simultaneous inhibition of UGT1A1 and CYP450 3A4 may lead to a clinically significant interaction with dolutegravir. In 12 study subjects, administration of dolutegravir (30 mg once daily) with the dual UGT1A1 and CYP450 3A4 inhibitor, atazanavir (400 mg once daily), increased dolutegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin; 24 hours postdose) by 50%, 91% and 180%, respectively, compared to administration without atazanavir. When the same dosage of dolutegravir was given with atazanavir/ritonavir 300 mg/100 mg once daily, the Cmax, AUC and Cmin of dolutegravir increased by 34%, 62% an 121%, respectively. Because safety data regarding increased dolutegravir exposures are limited, caution may be advisable if dolutegravir is used in combination with both a UGT1A1 inhibitor and a CYP450 3A4 inhibitor.

References

  1. (2013) "Product Information. Tivicay (dolutegravir)." ViiV Healthcare

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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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Minor

dolutegravir food

Applies to: Triumeq PD (abacavir / dolutegravir / lamivudine)

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.

References

  1. (2013) "Product Information. Tivicay (dolutegravir)." ViiV Healthcare

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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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