When procainamide and amiodarone are used together QTinterval prolonging effects are increased, therefore combination should generally be avoided. Serum procainamide levels areincreased by about 60 % and N-acetylprocainamide levels byabout 30 % by amiodarone. If combination is used, dosageof procainamide will need to be reduced to avoid toxicity.
Twelve patients were stabilised on procainamide (2 to 6 g daily,or about 900mg every 6 hours). When amiodarone (600 mg loading dose every 12 hrs for 5 to 7 days,then 600mg daily) was also given their mean serum procainamide levels rose by 57 % (from 6.8 to 10.6 micrograms/mL) and their serum levels of metabolite N-acetylprocainamide (NAPA) rose by 32 % (from 6.9 to 9.1 micrograms/mL). Procainamide levels increased by more than 3 micrograms/mL in 6 patients. The increases usually occurred within 24 hours,but in other patients they occurred as late as 4 or 5 days. Toxicity was seen in 2 patients. Despite lowering procainamide dosages by 20%, serum procainamide levels were still higher (at
7 micrograms/mL) than before amiodarone was started (See reference number 1)
In another study,intravenous procainamide was given once before (at a mean dose of 13 mg/kg), and once during (at a 30 % reduced dose: mean
9.2 mg/kg) use of amiodarone 1.6 g daily for 7 to 14 days. Amiodarone decreased clearance of procainamide by 23 % and increased its elimination half-life by 38%. Both drugs prolonged QRS and QTc intervals, and extent of prolongation was significantly greater with combination than either drug alone (See reference number 2).
The mechanism behind pharmacokinetic interaction is not understood. The QT prolonging effects of two drugs would be expected to be additive
Information appears to be limited to these studies, but interaction would seem to be established and clinically important. The use of amiodarone with procainamide further prolongs QTc interval, which can increase risk of torsade de pointes. Therefore, combination should generally be avoided. The UK manufacturers of amiodarone contraindicate its use with class Ia antiarrhythmics such as procainamide,(See reference number 3) whereas US manufacturers of amiodarone recommend that such combined therapy should be reserved for life-threatening ventricular arrhythmias incompletely responsive to either drug alone and recommend that procainamide dosage should be reduced by one-third (See reference number 4). See also Drugs that prolong QT interval + Other drugs that prolong QT interval interaction. This is similar to recommendation made by authors of pharmacokinetic studies, who suggest that dosage of procainamide may need to be reduced by 20 to 50%. They also suggest that serum levels should be monitored and patients observed for adverse effects (See reference number 1,2). Remember that interaction can develop within 24 hours.
Saal AK,Werner JA, Greene HL, Sears GK, Graham EL. Effect of amiodarone on serum quinidine and procainamide levels. Am J Cardiol (1984) 53, 1264–7.
Windle J,Prystowsky EN, Miles WM, Heger JJ. Pharmacokinetic and electrophysiologic interactions of amiodarone and procainamide. Clin Pharmacol Ther (1987) 41, 603–10.
Cordarone X (Amiodarone hydrochloride). Sanofi-Aventis. UK Summary of product characteristics,April 2006.
Cordarone (Amiodarone hydrochloride). Wyeth Pharmaceuticals. US Prescribing information,May 2007.