Basic Information
ID DDInter157 and DDInter76
Interaction Amiodarone can cause dose-related prolongation of the QT interval. Coadministration with other agents that can prolong the QT interval such as macrolide antibiotics may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Some macrolides such as clarithromycin, erythromycin, and troleandomycin are also potent inhibitors of CYP450 3A4 and may significantly inhibit the metabolism of amiodarone, which is primarily metabolized by the isoenzyme.
Management The concurrent use of amiodarone with other medications that can prolong the QT interval should generally be avoided unless benefits are anticipated to outweigh the risks. Caution and clinical monitoring are recommended if these agents are prescribed together, especially to patients with underlying risk factors. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope.
References [1] "Product Information. Azithromycin Product Information (azithromycin)." Pfizer US Pharmaceuticals, New York, NY. [2] Trivier JM, Libersa C, Belloc C, Lhermitte M "Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P450 3A enzymes (first report)." Life Sci 52 (1993): pl91-6 [3] Samarendra P, Kumari S, Evans SJ, Sacchi TJ, Navarro V "QT prolongation associated with azithromycin/amiodarone combination." Pacing Clin Electrophysiol 24 (2001): 1572-4 [4] Yamreudeewong W, DeBisschop M, Martin L, Lower D "Potentially Significant Drug Interactions of Class III Antiarrhythmic Drugs." Drug Saf 26 (2003): 421-38 [5] "Product Information. Erythrocin Lactobionate (erythromycin)." Abbott Pharmaceutical, Abbott Park, IL. [6] "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories, Philadelphia, PA. [7] Nattel S, Ranger S, Talajic M, et al "Erythromycin-induced long QT syndrome: concordance with quinidine and underlying cellular electrophysiologic mechanism." Am J Med 89 (1990): 235-8 [8] 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 [9] 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 [10] "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
Alternative for Azithromycin J01R
Tetracycline Cefixime

S01A
Tetracycline Ganciclovir Rifamycin Kanamycin Oxytetracycline Netilmicin
Polymyxin B Famciclovir Sulfamethizole
More
Alternative for Amiodarone C01B
Moricizine Tocainide Bretylium Mexiletine
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.