AMILORIDE

Fetal Risk Summary

Amiloride is a potassium-conserving diuretic. In general, diuretics are not recommended in the treatment of pregnancy-induced 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 (approximately 302 for the dihydrate, monohydrochloride salt) is low enough, however, that passage to the human fetus should be expected.

Three reports of fetal exposure to amiloride have been located (3,4 and 5) . 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.

The 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 retardation was detected at 30 weeks' gestation with eventual vaginal delivery of a 6-lb 2-ounce (about 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).

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.

[*Risk Factor D if used in pregnancy-induced hypertension.]

Breast Feeding Summary

Amiloride is excreted in the milk of lactating rats at concentrations higher than that measured in blood (1). No reports describing the use of the diuretic in lactating humans have been located. The molecular weight (approximately 302 for the dihydrate, monohydrochloride salt) is low enough, however, that passage into milk should be expected.

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.