Sotalol as a Hypotensive Agent in Pregnancy

Abstract

Sotalol, a beta-adrenoceptor blocking drug, was administered to 12 hypertensive pregnant women. The concentration of the drug was assayed in samples of maternal plasma, amniotic fluid and mixed umbilical cord plasma at delivery and, in five mothers who elected to breast feed, in paired samples of maternal plasma and breast milk. Sotalol reduced blood pressure effectively at a mean daily dose of 433.1 & 54 * 1 mg but crossed the placental barrier. The mean maternal: fetal plasma concentration ratio was 1 : 1.05 and the mean amniotic fluid concentration was 7 * 0 & 2 * 7 pg/ml. Delivery occurred at mean gestational age of 37 * 7 I 0 * 7 weeks ; 12 infants were liveborn with a mean weight of 2 . 8 k O . l kg and eight of them had no significant neonatal problems. Of the other four, two died from severe congenital anomalies, one had perinatal asphyxia and one mild transient hypoglycaemia. High sotalol concentrations were found in breast milk (mean plasma : milk ratio was 1 : 5 -4) raising the possibility of pharmacological effect in the newborn infant. The results suggest that sotalol adequately controls blood pressure in hypertension complicating pregnancy but because, unlike results from the pregnant ewe, it crosses the human placental barrier it offers no apparent advantages over other beta-adrenoceptor antagonists.

Developmental Toxicity in the Pregnant Rabbit by theClass III Antiarrhythmic Drug Sotalol

“…She delivered a normal baby. Two out of the remaining 11 babies were shown to have lethal congenital anomalies, but since treatment commenced after the first trimester, sotalol could not, according to the authors, be implicated for the large diaphragmatic hernia and duodenal atresia, respectively, in these babies (O'Hare et al 1980). However, hypoxia-related abnormalities could also be induced after organogenesis.…”

“…Sotalol has been shown to readily cross the placenta (O'Hare et al 1980;Erkkola et al 1982). It is reasonable to assume that the sotalol-exposed rabbit embryos die as a consequence of embryonic bradyarrhythmia/cardiac arrest, in the same way as has been proposed to happen after embryonic exposure to Ikr blockers in the rat.…”

“…In another study, twelve hypertensive women were treated with sotalol (O'Hare et al 1980). The mean amniotic concentration of sotalol (23 mM) in the study was half of the C max (46 mM) which caused developmental toxicity in this rabbit study, but conversely it was higher than the average 24 hr concentration (∂15 mM).…”

Excretion of sotalol in breast milk.

“…Infrequently, patients with these arrhythmias may also be women of child bearing age and hence the question of placental transfer and excretion in breast milk anses. Placental transfer of sotalol is well documented in a series of 12 patients and world experience of the transfer of sotalol into breast milk consists of a study in five patients (O'Hare et al, 1980).…”

Oxprenolol placental transfer, plasma concentrations in newborns and passage into breast milk.

“…A study with acebutolol (Bianchetti et al, 1981) showed that acebutolol crosses the placental barrier, resulting in a mean umbilical to maternal concentration ratio of 0.8. Sotalol also crosses the placental barrier, with a mean umbilical to maternal concentration ratio of 1 (O'Hare et al, 1980). In the newborns, blood was withdrawn (not from the cord) in the first 24 h after birth (for instance 1,4,6,9,11,14,16,19 or 22 h after birth).…”