Drug Interactions between amiodarone and Procanbid

GENERALLY AVOID: Coadministration of amiodarone and procainamide may increase the risk of new arrhythmias including torsade de pointes due to additive depressant effects on cardiac conduction, which could lead to excessive QT prolongation. Serious exacerbation of preexisting arrhythmia may also be more likely during coadministration relative to either agent alone. Pharmacokinetically, amiodarone may increase the plasma concentrations of procainamide and its active metabolite, N-acetylprocainamide (NAPA). The mechanism of interaction has not been established, but may involve inhibition of the hepatic metabolism and renal clearance of procainamide. In 12 patients stabilzed on procainamide (2 to 6 gm/day), the addition of amiodarone (600 mg every 12 hours for 5 to 7 days, followed by 600 mg daily) increased serum procainamide and NAPA concentrations by approximately 56% and 32%, respectively. The increases usually occurred within 24 hours, but took as long as 4 to 5 days. Toxicity was reported in two patients. Due to the long and variable half-life of amiodarone, potential for interaction may exist even after its discontinuation. In another study, eight patients with recurrent ventricular arrhythmias received a single IV dose of procainamide (6 to 15 mg/kg) during the initial control phase and after 1 to 2 weeks of amiodarone (1.6 gm/day). Relative to control, procainamide plasma clearance decreased by 23% and elimination half-life increased by 38% in the presence of amiodarone. Each agent individually produced equivalent increases in QRS duration, QTc interval, and cycle length of induced ventricular tachycardia. However, the increases were significantly greater with the combination than either drug alone, suggesting an additive electrophysiologic effect.

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

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