Hydroflumethiazide / reserpine Pregnancy and Breastfeeding Warnings

Brand names: Salutensin, Salutensin-Demi

Hydroflumethiazide / reserpine Pregnancy Warnings

Reserpine-hydroflumethiazide has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of teratogenicity after doses of reserpine 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 of reserpine 10 times the MRHD were given early or late in pregnancy. Animal reproduction studies have not been done with hydroflumethiazide. Some retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. There are no controlled data from human pregnancy. Reserpine-hydroflumethiazide should only be given during pregnancy when there are no alternatives and benefit outweighs risk.

There are three relevant sources of information regarding 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.

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 during pregnancy. There was no evidence of a 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, 4 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 often than expected.

Thiazide diuretics readily cross the human placenta, with umbilical cord blood thiazide levels approximately equivalent to maternal plasma thiazide levels.

Of the 50,282 mother-child pairs mentioned above, 233 were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics, although the fact that the population studied had underlying cardiovascular disease makes implication of drug use alone difficult. 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 defects (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 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 a related drug, hydrochlorothiazide (HCTZ). In the first study 29 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 HCTZ and congenital defects. These data are considered pertinent to other thiazide diuretics.

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

See references

Hydroflumethiazide / 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.

Thiazide diuretics are excreted into human milk in low concentrations. While a rare case of thrombocytopenia has been reported in one nursing infant whose mother was taking a related drug, chlorothiazide, adverse effects in the nursing infant are unlikely. The manufacturer recommends caution when administering hydroflumethiazide to nursing women.

See references

Further information

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