Sympatholytic (Antihypertensive)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Potential Toxicity
PREGNANCY SUMMARY
Prazosin is an α1-adrenergic blocking agent used for hypertension. The limited human pregnancy experience and the animal reproduction data suggest low embryo–fetal risk.
FETAL RISK SUMMARY
No evidence of teratogenicity was observed in reproduction studies with rats, rabbits, and monkeys at doses more than 225, 225, and 12 times, respectively, the usual maximum recommended human dose (1). A decreased litter size at birth in rats, however, was observed at the maximum dose.
The molecular weight of prazosin (about 384 for the free base) is low enough that transfer across the placenta to the embryo–fetus is likely. Consistent with this, a 1995 study using a 5-mg delayed-release formulation in three women measured umbilical cord blood concentrations at delivery that were 9%–23% of the maternal plasma levels 8–15 hours after the last dose (2).
In two studies, prazosin was combined with oxprenolol or atenolol, β-adrenergic blockers, in the treatment of pregnant women with severe essential hypertension or gestational hypertension (3,4). The combinations were effective in the first group but less so in the patients with gestational hypertension. No adverse effects attributable to the drugs were noted. Prazosin, 20 mg/day, was combined with minoxidil and metoprolol throughout gestation to treat severe maternal hypertension secondary to chronic nephritis (5). The child, normal except for hypertrichosis as a result of minoxidil, was doing well at 2 years of age.
Prazosin has been used during the 3rd trimester in patients with pheochromocytoma (6,7). In one case, blood pressure was well controlled, but maternal tachycardia required the addition of a β-blocker. A healthy male infant was delivered by cesarean section (6).
A case report published in 1986 described the pregnancy of a 24-year-old woman at 30 weeks’ gestation who was managed for recurrent pheochromocytoma with a combination of prazosin, metyrosine (a tyrosine hydroxylase inhibitor), and timolol (a β-adrenergic blocker) (7). Hypertension had been noted at her first prenatal visit at 12 weeks’ gestation. Because of declines in fetal breathing, body movements, and amniotic fluid volume that began 2 weeks after the start of therapy, a cesarean section was conducted at 33 weeks’. The 1450-g female infant had Apgar scores of 3 and 5 at 1 and 5 minutes, respectively. Mild metabolic acidosis was found on analysis of umbilical cord blood gases. Multiple infarcts were noted in the placenta but there was no evidence of metastatic tumor. The growth-restricted infant did well and was discharged home on day 53 of life (7).
BREASTFEEDING SUMMARY
No reports describing the use of prazosin during lactation have been located. The manufacturer reports that small amounts are excreted into human milk (1). This is consistent with the molecular weight (about 384 for the free base) of prazosin. The effects on a nursing infant from exposure to the drug from breast milk are unknown.
References
1.Product information. Minipress. Pfizer, 2000.
2.Bourget P, Fernandez H, Edouard D, Lesne-Hulin A, Ribou F, Baton-Saint-Mleux C, Lelaidier C. Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin. Eur J Drug Metab Pharmacokinet 1995;20:233–41.
3.Lubbe WF, Hodge JV. Combined alpha- and beta-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.Rosa FW, Idanpaan-Heikkila J, Asanti R. Fetal minoxidil exposure. Pediatrics 1987;80:120.
6.Venuto R, Burstein P, Schneider R. Pheochromocytoma: antepartum diagnosis and management with tumor resection in the puerperium. Am J Obstet Gynecol 1984;150:431–2.
7.Devoe LD, O’Dell BE, Castillo RA, Hadi HA, Searle N. Metastatic pheochromocytoma in pregnancy and fetal biophysical assessment after maternal administration of alpha-adrenergic, beta-adrenergic, and dopamine antagonists. Obstet Gynecol 1986;68:15S–8S.