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Drug Interactions between amiodarone and dofetilide

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

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Interactions between your drugs

Major

amiodarone dofetilide

Applies to: amiodarone and dofetilide

GENERALLY AVOID: Dofetilide should not be used with Class I or other Class III antiarrhythmic agents due to the potential for additive effects on myocardial refractoriness. Many of these agents, including dofetilide, can also cause prolongation of the QT interval, thus concomitant use may increase the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes.

MANAGEMENT: Class I (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, ibutilide, sotalol) antiarrhythmic agents should be withheld for at least 3 half-lives before administering dofetilide. In the case of amiodarone with its unpredictable pharmacokinetics, dofetilide should not be initiated until serum amiodarone levels are below 0.3 mcg/mL or amiodarone has been withdrawn for at least three months.

References (1)
  1. (2001) "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals

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
Minor

dofetilide food

Applies to: dofetilide

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.

References (1)
  1. (2001) "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiarrhythmics' category:

  • amiodarone
  • dofetilide

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Group iii antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'group III antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'group III antiarrhythmics' category:

  • amiodarone
  • dofetilide

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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.

Medical Disclaimer