BISOPROLOL

Fetal Risk Summary

Bisoprolol is a cardioselective b1-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) on a mg/kg and mg/m2 basis, 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 surface area, respectively (1). Embryo lethality (increased early resorptions) was observed in rabbits.

No reports describing the use of this antihypertensive agent in human pregnancy have been located. Some b-blockers may cause intrauterine growth retardation and reduced placental weight (e.g., see Atenolol and Propranolol). Treatment beginning early in the 2nd trimester results in the greatest weight reductions. This toxicity has not been consistently demonstrated in other agents within this class, but the relatively few pharmacologic differences among the drugs suggest that the reduction in fetal and placental weights probably occurs with all at some point. The lack of toxicity documentation may reflect the number and type of patients studied, the duration of therapy, or the dosage used, rather than a true difference among b-blockers. Although growth retardation is a serious concern, the benefits of maternal therapy with b-blockers may, in some cases, 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 b-blockade. Long-term effects of in utero exposure to b-blockers have not been studied but warrant evaluation.

[*Risk Factor D if used in 2nd or 3rd trimesters.]

Breast Feeding Summary

Bisoprolol is excreted into the milk of lactating rats (<2% of the dose) (1), but reports describing the use in lactating women or measuring the amount in human milk have not been located. Nursing infants of mothers consuming bisoprolol should be closely observed for hypotension, bradycardia, and other signs or symptoms of b-blockade. Long-term effects of exposure to b-blockers from milk have not been studied but warrant evaluation.

Reference