OXPRENOLOL

Fetal Risk Summary

Oxprenolol, a nonselective b-adrenergic blocking agent, has been used for the treatment of hypertension occurring during pregnancy (1,2,3 and 4). Oxprenolol and other b-blockers are generally considered safe and effective for this purpose by some reviewers (5,6). However, one reviewer recommended that agents with either cardioselectivity or a-blocking activity may be preferred to the nonselective blockers because these agents would be less likely to interfere with uterine perfusion (5). Other suggested guidelines governing the use of b-blockers in pregnancy were (a) if possible, avoid use in the 1st trimester; (b) use the lowest possible dose; and (c) if possible, discontinue the drugs 2–3 days before delivery (5). Oxprenolol crosses the placenta, but mean fetal serum levels at term are only about 25%–37% of maternal concentrations (4,6).

No fetal malformations or other fetal adverse effects attributable to oxprenolol have been reported, but experience during the 1st trimester is lacking. The drug has been compared with methyldopa in two studies of pregnant hypertensive women (1,2). In one of these studies, oxprenolol-exposed infants were significantly larger, 3051 g vs. 2654 g, than offspring of methyldopa-treated mothers (1). The difference was thought to be caused by the greater maternal plasma volume expansion and placental growth observed in the b-blocker group (1). In a follow-up report, the investigators noted that the differences between the two groups disappeared after 10 weeks of treatment (7). A 1983 study found no difference between oxprenolol- and methyldopa-treated groups in birth weight, placental weight, head circumference, and Apgar scores (2). In a third study, the combination of oxprenolol and prazosin (an a-adrenergic blocking agent) was effective for the control of severe essential hypertension in 25 pregnant women but not effective in 19 patients with pregnancy-induced hypertension (3).

Although b-blockade of the newborn has not been reported in the offspring of oxprenolol-treated mothers, this complication has occurred with other members of this class (see Acebutolol, Atenolol, and Nadolol). Thus, close observation of the newborn for bradycardia and other symptoms of b-blockade is recommended during the first 24–48 hours after birth. Long-term effects of in utero exposure to b-blockers have not been studied but warrant evaluation.

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 suggests 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 then 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.

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

Breast Feeding Summary

Oxprenolol is excreted into breast milk (8,9). In nine lactating women given 80 mg twice daily, the mean milk concentration of oxprenolol 105–135 minutes after a dose was 118 ng/mL (9). When a dose of 160 mg twice daily was given to three women, mean milk levels were 160 ng/mL. Finally, one woman was treated with 320 mg twice daily, producing a milk level of 470 ng/mL. The milk:plasma ratios for the three regimens were 0.14, 0.16, and 0.43, respectively. The mean milk:plasma ratio in another study was 0.45 (8). These low ratios, relative to other b-blockers, may be caused by the high maternal serum protein binding (80%) that negates trapping of the weakly basic drug in the relatively acidic milk (8). Based on calculations, a mother ingesting 240 mg/day would provide a 3-kg infant with a dose of 0.07 mg/kg in 500 mL of milk (8). This amount is probably clinically insignificant.

Although no adverse reactions have been noted in nursing infants of mothers treated with oxprenolol, infants should be closely observed for bradycardia and other symptoms of b-blockade. Long-term effects of exposure to b-blockers from milk have not been studied but warrant evaluation. The American Academy of Pediatrics considers oxprenolol to be compatible with breast feeding (10).

References

1. Gallery EDM, Saunders DM, Hunyor SN, Gyory AZ. Randomized comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy. Br Med J 1979;1:1591–4.
2. Fidler J, Smith V, Fayers P, DeSwiet M. Randomized controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy. Br Med J 1983;286:1927–30.
3. Lubbe WF, Hodge JV. Combined a- and b-adrenoceptor antagonism with prazosin and oxprenolol in control of severe hypertension in pregnancy. NZ Med J 1981;94:169–72.
4. Lubbe WF. More on beta-blockers in pregnancy. N Engl J Med 1982;307:753.
5. Frishman WH, Chesner M. Beta-adrenergic blockers in pregnancy. Am Heart J 1988;115:147–52.
6. Gallery EDM. Hypertension in pregnant women. Med J Aust 1985;143:23–7.
7. Gallery EDM, Ross MR, Gyory AZ. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. Br Med J 1985;291:563–6.
8. Sioufi A, Hillion D, Lumbroso P, Wainer R, Olivier-Martin M, Schoeller JP, Colussi D, Leroux F, Mangoni P. Oxprenolol placental transfer, plasma concentrations in newborns and passage into breast milk. Br J Clin Pharmacol 1984;18:453–6.
9. Fidler J, Smith V, DeSwiet M. Excretion of oxprenolol and timolol in breast milk. Br J Obstet Gynaecol 1983;90:961–5.
10. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.