Sympatholytic (Antihypertensive)
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 2nd and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: Limited Human Data—Potential Toxicity
PREGNANCY SUMMARY
In one study, betaxolol was started in the 3rd trimester and no fetal harm was observed. 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. Betaxolol does not possess ISA. 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. If used near delivery, the newborn infant should be closely monitored 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
Betaxolol is a cardioselective β1-adrenergic blocking agent used in the treatment of hypertension and topically in the therapy of glaucoma. Betaxolol is teratogenic in rats producing skeletal and visceral anomalies at maternally toxic doses (600 times the maximum recommended human dose [MRHD]) (1). At this dose, postimplantation loss and reduced litter size and weight were also noted. At doses 6 and 60 times the MRHD, a possible increased incidence of incomplete descent of testes and sternebral reductions were observed (1). No teratogenic effects were observed in rabbits, but an increase in postimplantation loss occurred at the highest dose tested (54 times the MRHD) (1).
Betaxolol rapidly crosses the human placenta (2–4). The mean fetal:maternal ratio at birth was 0.93. The half-life in newborns was 14.8–38.5 hours compared with that in the mothers of 15.6–22.1 hours (mean 19 hours) (2,3).
A 1990 report from France described the pregnancy outcomes of 22 women treated with betaxolol (10–40 mg/day) for mild to moderate hypertension (4). Treatment was begun at a mean of 30.7 weeks. The mean gestational age at birth was 37.2 weeks and the mean birth weight of the 23 neonates (1 set of twins) was 2.6 kg. One of the newborns was growth restricted (onset before betaxolol therapy) and five were premature. All were doing well at 9 months (4).
BREASTFEEDING SUMMARY
Betaxolol is excreted into human milk in quantities sufficient to produce β-blockade in a nursing infant (1). Although no reports have been located that describe the use of this agent during nursing, one study measured betaxolol concentrations in the milk of three mothers who had been treated with drug during pregnancy in the first 3 postpartum days (3). The last maternal dose had been taken 3–26 hours before delivery. The milk concentrations ranged from 3 to 48 ng/mL and the milk:plasma ratios ranged from 2.0 to 11.6, with the highest ratios occurring in one mother 48 and 72 hours after delivery. No mention was made if the mothers breastfed their infants
If betaxolol is used during nursing, the infant 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. Kerlone. G.D. Searle & Co., 1997.
2.Morselli PL, Boutroy MJ, Bianchetti G, Thenot JP. Pharmacokinetics of antihypertensive drugs in the neonatal period. Dev Pharmacol Ther 1989;13:190–8.
3.Morselli PL, Boutroy MJ, Bianchetti G, Zipfel A, Boutroy JL, Vert P. Placental transfer and perinatal pharmacokinetics of betaxolol. Eur J Clin Pharmacol 1990;38:477–83.
4.Boutroy MJ, Morselli PL, Bianchetti G, Boutroy JL, Pepin L, Zipfel A. Betaxolol: a pilot study of its pharmacological and therapeutic properties in pregnancy. Eur J Clin Pharmacol 1990;38:535–9.