Risk Factor: CM
Class: Cardiovascular drugs/ Cardiac drugs
Fetal Risk Summary
Procainamide is a cardiac drug used for the termination and prophylaxis of atrial and ventricular tachyarrhythmias (1). Animal reproduction studies with procainamide have not been conducted. The use of procainamide during human pregnancy has not been associated with congenital anomalies or other adverse fetal effects (1,2,3,4,5,6, 7,8 and 9).
Successful cardioversion with procainamide of a fetal supraventricular tachycardia presenting at 30 weeks’ gestation has been reported (4). Therapy with digoxin alone and digoxin combined with propranolol failed to halt the arrhythmia. Procainamide was then combined with digoxin, resulting in cardioversion to a sinus rhythm and resolution of fetal ascites and pericardial effusion. During the following 3 weeks, the mother was maintained on oral procainamide, 1 g every 6 hours, and digoxin. Maternal serum levels of procainamide varied from 2.4 to 4.1 g/mL. The abnormal rhythm returned at 33 weeks’ gestation, and control became increasingly difficult. Additional therapy with procainamide increased the maternal serum concentration to 6.8 g/mL. During the last 24 hours, four IV bolus doses of procainamide (700 mg 3 times, 650 mg once) were administered plus a maintenance dose of 3 mg/minute. Three hours after the last bolus dose, a 2650-g female infant was delivered by cesarean section. Serum procainamide concentrations in the newborn and mother were 4.3 and 15.6 g/mL, respectively, a ratio of 0.28. During the subsequent neonatal course, the infant was successfully treated for congestive heart failure and persistent supraventricular tachycardia. The electrocardiogram was normal at 6 months of age.
In a case similar to the one described above, therapy with digoxin, verapamil, and procainamide failed to control fetal supraventricular tachycardia presenting at 24 weeks’ gestation (5). At cordocentesis, procainamide concentrations in the fetus and mother were 11.7 and 12.8 g/mL (ratio 0.91), respectively. Levels of the active metabolite, N-acetylprocainamide, were 3.0 and 3.5 g/mL (ratio 0.86), respectively. Cardioversion was eventually accomplished with direct fetal digitalization by periodic IM injection.
Procainamide was prescribed for a woman in her 24th week of gestation for ventricular tachycardia (7). She was treated with doses up to 2000 mg every 6 hours, combined with metoprolol 100 mg every 12 hours, until delivery of a healthy, 3155-g girl at 38 weeks’ gestation. Maternal and mixed cord blood concentrations of procainamide were 6.0 and 6.4 g/mL (fetal:maternal ratio 1.1), respectively. Similar analysis for N-acetylprocainamide yielded levels of 9.4 and 8.7 g/mL (ratio 0.9), respectively. No fetal or newborn adverse effects were observed.
Breast Feeding Summary
Procainamide and its active metabolite, N-acetylprocainamide, are accumulated in breast milk (10). A woman was treated with procainamide, 375 mg 4 times daily, for premature ventricular contractions during the 3rd trimester (10). The dose was increased to 500 mg 4 times daily 1 week before delivery at 39 weeks’ gestation. Simultaneous serum and milk samples were obtained in the postpartum period (exact time not specified) every 3 hours for a total of 15 hours. Procainamide (500 mg) was administered orally at hours 0, 6, and 12 immediately after samples were obtained. Mean serum concentrations of procainamide and N-acetylprocainamide were 1.1 and 1.6 g/mL, respectively, while the concentrations in the milk were 5.4 and 3.5 g/mL, respectively. The mean milk:serum ratios for the parent drug and the metabolite were 4.3 (range 1.07.3) and 3.8 (range 1.06.2), respectively. The amount of drug available to the nursing infant, based on a hypothetical serum level of 8 g/mL, was estimated to be 64.8 g/mL (procainamide plus metabolite). Assuming the infant could ingest 1000 mL of milk/day (thought to be unlikely), this would only provide about 65 mg of total active drug. This amount was not expected to yield clinically significant serum concentrations (10). The American Academy of Pediatrics considers procainamide to be compatible with breast feeding (11). However, the long-term effects of exposure in the nursing infant to procainamide and its metabolites are unknown, particularly in regard to potential drug toxicity (e.g., development of antinuclear antibodies and lupus-like syndrome).
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