Sympatholytic (Antihypertensive)
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 2nd and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Some β-blockers may cause intrauterine growth restriction (IUGR) and reduced placental weight, especially those lacking intrinsic sympathomimetic activity (ISA) (i.e., partial agonist). Treatment beginning early in the 2nd trimester results in the greatest weight reductions, whereas treatment restricted to the 3rd trimester primarily affects only placental weight. However, IUGR and reduced placental weight may potentially occur with all agents within this class. Although growth restriction is a serious concern, the benefits of maternal therapy with β-blockers, in some cases, might outweigh the risks to the fetus and must be judged on a case-by-case basis.
Newborn infants of mothers consuming the drug near delivery should be closely observed for 24–48 hours for signs and symptoms of β-blockade. Long-term effects of in utero exposure to β-blockers have not been studied but warrant evaluation.
FETAL RISK SUMMARY
Bisoprolol is a cardioselective β1-adrenergic blocking agent used in the management of hypertension. In animal reproduction studies, bisoprolol was not teratogenic in rats at doses up to 375 and 77 times the maximum recommended human dose (MRHD) based on weight and BSA, respectively, but fetotoxicity (increased late resorptions) was observed (1). No teratogenic effects were observed in rabbits at doses up to 31 and 12 times the MRHD based on body weight and BSA, respectively (1). Embryo lethality (increased early resorptions) was observed in rabbits.
A 2004 case report described a 24-year-old woman who took bisoprolol (5 mg/day), naproxen (550 mg about twice a week), and sumatriptan (100 mg about once a week) for migraine headaches during the first 5 weeks of pregnancy (2). An elective cesarean section was performed at 37 weeks for breech presentation to deliver a 3125-g male infant. The infant had a wide bilateral cleft lip/palate, marked hypertelorism, a broad nose, and bilateral but asymmetric toe abnormalities (missing and hypoplastic phalanges) (2).
BREASTFEEDING SUMMARY
No reports describing the use of bisoprolol in lactating women have been located. Nursing infants of mothers consuming bisoprolol should be closely observed for hypotension, bradycardia, and other signs or symptoms of β-blockade. Long-term effects of exposure to β-blockers from milk have not been studied but warrant evaluation.
References
1.Product information. Zebeta. Lederle Laboratories, 1997.
2.Kajantie E, Somer M. Bilateral cleft lip and palate, hypertelorism and hypoplastic toes. Clin Dysmorphol 2004;13:195–6.