Spironolactone in Pregnancy and Breastfeeding
Fetal Risk Summary
Spironolactone, a potassium-conserving diuretic, has an action that results from its antagonism of aldosterone in the distal convoluted renal tubule. The diuretic action results in an antihypertensive effect. Spironolactone also has progestational and anti-androgenic activity. The latter activity may result in apparent estrogenic adverse effects in humans (1).
Reproduction studies in mice at 20 mg/kg/day, a dose substantially below the maximum recommended human dose on a body surface area basis (MRHD), revealed no embryo or fetal adverse effects (1). In rabbits dosed at 20 mg/kg/day (approximately the MRHD), an increased number of resorptions and lower number of live fetuses was observed. Because of spironolactone's anti-androgenic activity, feminization of male rat fetuses occurred at a dose of 200 mg/kg/day administered to the mothers during late embryogenesis and fetal development (1). In addition, rat offspring of both sexes exposed in utero in late gestation to 50 or 100 mg/kg/day exhibited permanent dose-related changes in their reproductive tracts (1).
No reports linking spironolactone with human congenital defects have been located. Some have commented, however, that spironolactone may be contraindicated during pregnancy based on the known anti-androgenic effects in humans and the feminization observed in male rat fetuses (2). Other investigators consider diuretics in general to be contraindicated in pregnancy, except for patients with cardiovascular disorders, because they do not prevent or alter the course of toxemia and they may decrease placental perfusion (3,4 and 5). In general, diuretics are not recommended for the treatment of pregnancy-induced hypertension because of the maternal hypovolemia characteristic of this disease.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 31 newborns had been exposed to spironolactone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Two (6.5%) major birth defects were observed (one expected), one of which was an oral cleft (none expected). No anomalies were observed in five other categories of defects (cardiovascular defects, spina bifida, polydactyly, limb-reduction defects, and hypospadias) for which specific data were available.
[*Risk Factor D if used in pregnancy-induced hypertension.]
Breast Feeding Summary
It is not known whether unmetabolized spironolactone is excreted in breast milk. Canrenone, the principal and active metabolite, was found with milk:plasma ratios of 0.72 (2 hours) and 0.51 (14.5 hours) (6). These amounts would provide an estimated maximum of 0.2% of the mother's daily dose to the infant (6). The effects on the infant from this ingestion are unknown. However, consideration should be given to the fact that spironolactone is tumorigenic in rats (1). The American Academy of Pediatrics considers spironolactone to be compatible with breast feeding (7).
- Product information. Aldactone. G.D. Searle, 2000.
- Messina M, Biffignandi P, Ghiga E, Jeantet MG, Molinatti GM. Possible contraindication of spironolactone during pregnancy. J Endocrinol Invest 1979;2:222.
- Pitkin RM, Kaminetzky HA, Newton M, Pritchard JA. Maternal nutrition: a selective review of clinical topics. Obstet Gynecol 1972;40:77385.
- Lindheimer MD, Katz AI. Sodium and diuretics in pregnancy. N Engl J Med 1973;288:8914.
- Christianson R, Page EW. Diuretic drugs and pregnancy. Obstet Gynecol 1976;48:64752.
- Phelps DL, Karim A. Spironolactone: relationship between concentrations of dethioacetylated metabolite in human serum and milk. J Pharm Sci 1977;66:1203.
Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.