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Drug Interactions between amiodarone and Mexitil

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

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Interactions between your drugs

Moderate

amiodarone mexiletine

Applies to: amiodarone and Mexitil (mexiletine)

ADJUST DOSE: Coadministration of amiodarone and mexiletine has been associated with an isolated case of torsade de pointes. The mechanism of interaction is unknown, as mexiletine has not been shown to prolong the QT interval of the electrocardiogram. In fact, mexiletine has been used in the treatment of torsade de pointes. A study of patients with supraventricular tachyarrhythmias treated with a combination of amiodarone and mexiletine or mexiletine alone found no evidence of a pharmacokinetic interaction. Some investigators have also reported on the safe and effective use of the combination.

MANAGEMENT: In general, the concurrent use of amiodarone with other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent or to amiodarone alone. If adding or transferring to amiodarone, the dosages of previously administered agents should be reduced by 30% to 50% several days after the addition of amiodarone, when onset of arrhythmia suppression should occur. The continued need for other antiarrhythmic agents should be evaluated after the effects of amiodarone have been established, and discontinuation should generally be attempted. If the combination is continued, patients should be monitored for adverse effects including conduction disturbances and exacerbation of tachyarrhythmias. In amiodarone-treated patients who require additional antiarrhythmic agents, the initial dosage of such agents should be approximately one-half the usual recommended dosage.

References

  1. Marcus FI (1983) "Drug interactions with amiodarone." Am Heart J, 106, p. 924-30
  2. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  3. Yonezawa E, Matsumoto K, Ueno K, et al. (2002) "Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients." J Clin Pharmacol, 42, p. 342-6
  4. Waleffe A, Mary-Rabine L, Legrand V, Demoulin JC, Kulbertus HE (1980) "Combined mexiletine and amiodarone treatment of refractory recurrent ventricular tachycardia." Am Heart J, 100, p. 788-93
  5. Hoffman A, Follathe F, Burckhardt D (1983) "Safe treatment of resistant ventricular arrhythmias with a combination of amiodarone and quinidine or mexiletine." Lancet, i, p. 704
View all 5 references

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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

  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

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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
  • Mexitil (mexiletine)

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.

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