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Drug Interactions between amiodarone and fluvastatin

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

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Interactions between your drugs

Moderate

amiodarone fluvastatin

Applies to: amiodarone and fluvastatin

MONITOR: Coadministration with inhibitors of CYP450 2C9 may increase the plasma concentrations of fluvastatin. According to the prescribing information, fluvastatin is primarily metabolized by CYP450 2C9 (approximately 75%) and, to a much lesser extent, by CYP450 2C8 and 3A4 (approximately 5% and 20%, respectively). When a single 40 mg oral dose of fluvastatin was administered on day 4 of treatment with the moderate CYP450 2C9 inhibitor fluconazole (400 mg orally on day 1 and 200 mg on days 2 to 4) in 12 healthy study subjects, mean fluvastatin peak plasma concentration (Cmax), systemic exposure (AUC) and elimination half-life (t1/2) increased by 44%, 84% and 80%, respectively, compared to administration with placebo. Fluconazole is also a moderate CYP450 3A4 inhibitor, which may have contributed to the interaction. In a similar study conducted by the same investigators, fluconazole had no significant effect on the pharmacokinetics of a single 40 mg oral dose of pravastatin.

MANAGEMENT: Caution is advised when fluvastatin is prescribed with CYP450 2C9 inhibitors. The lowest starting dosage of fluvastatin is recommended, then titrated as needed based on clinical response and tolerance. Alternatively, pravastatin is not metabolized by CYP450 2C9 and may be a reasonable substitute for fluvastatin. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References (4)
  1. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  2. Kantola T, Backman JT, Niemi M, Kivisto KT, Neuvonen PJ (2000) "Effect of fluconazole on plasma fluvastatin and pravastatin concentrations." Eur J Clin Pharmacol, 56, p. 225-9
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Major

amiodarone food

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

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.

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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

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