Diuretic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Similar to other diuretics, amiloride does not appear to pose a risk to the embryo–fetus when used for indications other than gestational hypertension or preeclampsia.
FETAL RISK SUMMARY
Amiloride is a potassium-conserving diuretic. In general, diuretics are not recommended in the treatment of gestational hypertension because of the maternal hypovolemia characteristic of this disease.
Reproduction studies using amiloride alone in mice at 25 times the maximum recommended human dose (MRHD) and in rabbits at 20 times the MRHD found no evidence of fetal harm (1). The combination of acetazolamide and amiloride was found to produce abnormal development of the ureter and kidney in fetal mice when given at the critical moment of ureter development (2).
Amiloride crosses the placenta in modest amounts in mice and rabbits (1). No reports describing the human placenta passage of amiloride have been located. The molecular weight (about 230 for the free base) suggests that drug will cross the placenta.
Seven reports of fetal exposure to amiloride have been located (3–9). In one case, a malformed fetus was discovered after voluntary abortion in a patient with renovascular hypertension (3). The patient had been treated during the 1st trimester with amiloride, propranolol, and captopril. The left leg of the fetus ended at midthigh without distal development and no obvious skull formation was noted above the brain tissue. The authors attributed the defects to captopril (3), but this agent is not thought to cause birth defects in the 1st trimester.
A second case involved a 21-year-old woman with Bartter’s syndrome who was maintained on amiloride (20–30 mg/day) and potassium chloride (160–300 mEq/day) throughout pregnancy (4). Progressive therapy with the two agents was required to maintain normal potassium levels. Mild intrauterine growth restriction was detected at 30 weeks’ gestation with eventual vaginal delivery of a 2800-g female infant at 41 weeks’ gestation. No abnormalities were noted in the infant. A normal 3500-g female infant was delivered by cesarean section at 37 weeks’ gestation from a mother who had been treated throughout pregnancy with amiloride, hydrochlorothiazide, and amiodarone for severe chronic atrial fibrillation (5). A second case with Bartter’s syndrome was reported in 2004 (6). Amiloride was used throughout the pregnancy and a healthy 3.300-kg female infant was born at term.
Two cases of Gitelman syndrome, an inherited hypokalemic salt-losing renal tubular disorder that is closely related to Bartter’s syndrome, that were treated with amiloride have been located (7,8). Both pregnancy outcomes were normal babies born at 37 weeks’ gestation.
A woman with primary aldosteronism had two pregnancies that were treated with amiloride (9). Both pregnancies ended with the birth of a healthy infant.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 28 newborns had been exposed to amiloride during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Two (7.1%) major birth defects were observed (one expected), one of which was a hypospadias. No anomalies were observed in five other categories of defects (cardiovascular, oral clefts, spina bifida, polydactyly, and limb reduction defects) for which specific data were available.
BREASTFEEDING SUMMARY
No reports describing the use of amiloride during human lactation have been located. The molecular weight (about 230 for the free base) suggests that excretion into breast milk will occur.
References
1.Product information. Midamor. Merck, 2000.
2.Miller TA, Scott WJ Jr. Abnormalities in ureter and kidney development in mice given acetazolamide–amiloride or dimethadione (DMO) during embryogenesis. Teratology 1992;46:541–50.
3.Duminy PC, Burger PT. Fetal abnormality associated with the use of captopril during pregnancy. S Afr Med J 1981;60:805.
4.Almeida OD Jr, Spinnato JA. Maternal Bartter’s syndrome and pregnancy. Am J Obstet Gynecol 1989;160:1225–6.
5.Robson DJ, Jeeva Raj MV, Storey GCA, Holt DW. Use of amiodarone during pregnancy. Postgrad Med J 1985;61:75–7.
6.Deruelle P, Dufour P, Magnenant E, Courouble N, Puech F. Maternal Bartter’s syndrome in pregnancy treated with amiloride. Eur J Obstet Gynecol Reprod Biol 2004;115;106–7.
7.Mascetti L, Bettinelli A, Simonetti GD, Tagliabue A, Syren ML, Nordio F, Bianchetti MG. Pregnancy in inherited hypokalemic salt-losing renal tubular disorder. Obstet Gynecol 2011;117:512–6.
8.Mathen S, Venning M, Gillham J. Outpatient management of Gitelman’s syndrome in pregnancy. BMJ Case Rep. Jan 25;2013. pii:bcr2012007927. doi:10.1136/bcr-2012-007927.
9.Krysiak R, Samborek M, Stojko R. Primary aldosteronism in pregnancy. Acta Clin Belg 2012;67:130–4.