Antiarrhythmic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Four reports and a review have described the use of propafenone in late pregnancy (1–5). There is no reported experience in the 1st trimester. No adverse effects were observed in the fetus or the newborn.
FETAL RISK SUMMARY
Propafenone is an orally active antiarrhythmic used in the treatment of ventricular tachycardia. The agent has an active metabolite, 5-OH-propafenone. No teratogenic effects have been observed in studies with rabbits and rats, but propafenone was embryotoxic in both species when given in doses of 10 and 40 times the maximum recommended human dose, respectively (6).
Propafenone crosses the human placenta at term (1). A woman, delivering at 36 weeks’ gestation, was taking 300 mg 3 times daily in the 3rd trimester. Trough concentrations of propafenone and its active metabolite in the mother were 145 and 69 ng/mL, respectively, and in the newborn were 30 and 29 ng/mL, respectively.
BREASTFEEDING SUMMARY
Propafenone is excreted into breast milk. A woman took propafenone 300 mg 3 times a day during the latter part of pregnancy and during breastfeeding (1). Three days postpartum, trough concentrations of propafenone and its active metabolite were 32 and 47 ng/mL, respectively, whereas the maternal plasma levels were 219 and 86 ng/mL, respectively.
In a 2005 study, a single oral dose of propafenone 150 mg was given to a nursing mother (7). The infant was not allowed to breastfeed during the study. Six paired samples of milk and maternal plasma were drawn over 12 hours. The milk:plasma ratio, based on AUC, was 0.25, and the relative infant dose was 0.1% of the mother’s weight-adjusted dose (7).
References
1.Libardoni M, Piovan D, Busato E, Padrini R. Transfer of propafenone and 5-OH-propafenone to foetal plasma and maternal milk. Br J Clin Pharmacol 1991;32:527–8.
2.Brunozzi LT, Meniconi L, Chiocchi P, Liberati R, Zuanetti G, Latini R. Propafenone in the treatment of chronic ventricular arrhythmias in a pregnant patient. Br J Clin Pharmacol 1988;26:489–90.
3.Santinelli V, De Paola M, Turco P, Smimmo D, Chiariello M, Condorelli M. Wolff-Parkinson-White at risk and propafenone. J Am Coll Cardiol 1988;11:1138.
4.Gembruch U, Manz M, Bald R, Rüddel H, Redel DA, Schlebusch H, Nitsch J, Hansmann M. Repeated intravascular treatment with amiodarone in a fetus with refractory supraventricular tachycardia and hydrops fetalis. Am Heart J 1989;118:1335–8.
5.Capucci A. Boriani G. Propafenone in the treatment of cardiac arrhythmias. A risk-benefit appraisal. Drug Saf 1995;12:55–72.
6.Product information. Rythmol. Knoll Pharmaceuticals, 2000.
7.Wakaumi M, Tsuruoka S, Sakamoto K, Shigal T, Fujimura A. Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone. Br J Clin Pharmacol 2005;59:120–2.