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Drug Interactions between Cordarone IV and lesinurad

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

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Interactions between your drugs

Moderate

amiodarone lesinurad

Applies to: Cordarone IV (amiodarone) and lesinurad

MONITOR: Coadministration with inhibitors of CYP450 2C9 may increase the plasma concentrations of lesinurad, which is primarily metabolized by the isoenzyme. According to the manufacturer, administration of lesinurad with the moderate CYP450 2C9 inhibitor fluconazole (200 mg daily) increased lesinurad peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 35% and 55%, respectively, compared to administration of lesinurad alone. In a cross-study pharmacogenomic analysis conducted in patients receiving single or multiple doses of lesinurad, patients who were deficient in CYP450 2C9 activity (i.e., CYP450 2C9 poor metabolizers) had an approximately 1.8-fold higher exposure to lesinurad at the 400 mg dose than extensive metabolizers.

MANAGEMENT: Caution is advised when lesinurad is prescribed with CYP450 2C9 inhibitors. Patients should be closely monitored for adverse renal effects such as serum creatinine elevations, renal function impairment, and nephrolithiasis. It may be advisable to avoid concomitant use with a potent CYP450 2C9 inhibitor such as gemfibrozil.

References

  1. "Product Information. Zurampic (lesinurad)." Astra-Zeneca Pharmaceuticals (2015):

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Drug and food interactions

Major

amiodarone food

Applies to: Cordarone IV (amiodarone)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.

ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.

MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.

References

  1. "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories PROD (2002):
  2. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  3. Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR "Bioavailability of Amiodarone tablets administered with and without food in healthy subjects." Am J Cardiol 87 (2001): 432-5

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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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