Hydrochlorothiazide / reserpine Pregnancy and Breastfeeding Warnings

Brand names: Hydro-Reserp, Hydropres-25, Hydropres-50, Hydroserp, Hydroserpine, Hydroserpine 1

Hydrochlorothiazide / reserpine Pregnancy Warnings

Reserpine-hydrochlorothiazide (HCTZ) has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of teratogenicity after doses 125 to 250 times the maximum recommended human dose (MRHD, on a per kg basis) were given to rats. Abnormalities included anophthalmia, absence of the axial skeleton, and hydronephrosis. Pregnancy in rabbits was interrupted when doses 10 times the MRHD were given early or late in pregnancy. There are no controlled data from human pregnancy. Reserpine should only be used during pregnancy when there are no alternatives and benefit outweighs risk.

There are three relevant sources of information on the use of reserpine during human pregnancy.

In one case report, a stillborn female was born at gestation week 30 to a hypertensive, 30-year-old mother who had taken reserpine from days 13 to 41. Abnormalities included cleft lip and palate and bilateral anophthalmia, marked scoliosis, a thoracolumbar open defect, and diaphragmatic agenesis. The mother had also been exposed to tobacco and ampicillin.

In response to this case report, Cziezel summarized the Hungarian experience with reserpine from 1980 to 1984. During this period, 52 of 6,227 pregnant women were exposed to reserpine. Neither the total group nor subgroups of congenital anomalies indicated a significant increase associated with reserpine treatment during pregnancy. There was no evidence of any congenital reserpine syndrome.

Of 50,282 mother-child pairs monitored by the Collaborative Perinatal Project, 48 had first trimester exposure to reserpine and 475 had exposure to reserpine at anytime during pregnancy. Of the 48, four defects (8%) were observed, which was more than expected. Of the 475, microcephaly (7), hydronephrosis (3), inguinal hernia (12), and hydroureter (3), were observed. None of these anomalies occurred significantly more than expected.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, of whom 233 were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics. Use of thiazides after the first trimester does not seem to carry this risk. Thiazide diuretics may, however pose metabolic risks to the mother and fetus (hyponatremia, hypokalemia, thrombocytopenia, hyperglycemia), and may have a direct effect on smooth muscle, resulting in inhibition of labor.

The Michigan Medicaid surveillance study showed no association between reserpine or thiazide diuretics and congenital abnormalities (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). Of 229,101 completed pregnancies between 1985 and 1992, 15 were exposed to reserpine at some time during the first trimester, and 42 were exposed to the drug at any time during pregnancy. No birth defects were observed. Regarding thiazide diuretics, this report is a summary of information from two studies, one in which 390 of 104,000 pregnant women from 1980 to 1983, and one in which 567 of 229,101 pregnant women from 1985 to 1992 received HCTZ. In the first study 28 total defects and 6 cardiovascular defects were observed (25 and 4 were expected, respectively). In the second study, 24 total defects and 7 cardiovascular defects were observed (22 and 6 were expected, respectively). Cleft palate was not observed in either study. These data do not support an association between reserpine or thiazide diuretics and congenital defects.

Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

See references

Hydrochlorothiazide / reserpine Breastfeeding Warnings

Reserpine is excreted into human milk. There are no reports of adverse effects on the nursing infant. There is a report of galactorrhea associated with reserpine.

Hydrochlorothiazide (HCTZ) is secreted into human milk in low concentrations. Adverse effects in the nursing infant are unlikely. HCTZ is considered compatible with breast-feeding by the American Academy of Pediatrics; however, the manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

In on case a peak milk concentration of 125 ng/mL was measured between 4 and 12 hours after a daily dose in a woman who was taking HCTZ 50 mg/day. A simultaneously measured maternal serum HCTZ level was approximately 275 ng/mL. There were no detectable drug levels or electrolyte abnormalities in the baby's blood. The authors calculated that, if a 1-month-old infant takes approximately 600 mL of milk per day, and the mean milk HCTZ level is approximately 80 ng/mL, the infant would be exposed to approximately 0.05 mg HCTZ daily. This should represent an insignificant amount of HCTZ to the infant such that adverse effects in the nursing infant are unlikely.

See references

Further information

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