Diuretic
PREGNANCY RECOMMENDATION: Human Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Many investigators consider diuretics to be contraindicated in pregnancy, except for patients with heart disease, because they do not prevent or alter the course of toxemia, and they may decrease placental perfusion (1–3). In general, diuretics are not recommended for the treatment of gestational hypertension because of the maternal hypovolemia characteristic of this disease. Folic acid, at least 0.4 mg/day, should be taken before and during gestation because triamcinolone is a weak folic acid inhibitor.
FETAL RISK SUMMARY
Triamterene is a potassium-conserving diuretic. It is a weak folic acid antagonist. Reproduction studies in rats at doses up to 6 times the maximum recommended human dose based on BSA found no evidence of fetal harm (4).
It is not known if triamterene crosses the human placenta. The molecular weight (about 253) is low enough that exposure of the embryo–fetus should be expected.
No defects were observed in five infants exposed to triamterene in the 1st trimester (5, p. 372). For use anytime during pregnancy, 271 exposures were recorded without an increase in malformations (5, p. 441).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 318 newborns had been exposed to triamterene during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 15 (4.7%) major birth defects were observed (13 expected). Three cases of cardiovascular defects (three expected) and one case of polydactyly (one expected) were observed, but specific information was not available for the other defects. No anomalies were observed in four other categories of defects (oral clefts, spina bifida, limb reduction defects, and hypospadias) for which data were available. These data do not support an association between the drug and congenital defects.
The effects of exposure (at any time during the 2nd or 3rd month after the last menstrual period) to folic acid antagonists on embryo–fetal development were evaluated in a large, multicenter, case–control surveillance study published in 2000 (6). The report was based on data collected between 1976 and 1998 by the Slone Epidemiology Unit Birth Defects Study from 80 maternity or tertiary care hospitals in Boston, Philadelphia, Toronto, and Iowa. Mothers were interviewed within 6 months of delivery about their use of drugs during pregnancy. Folic acid antagonists were categorized into two groups: group I—dihydrofolate reductase inhibitors (aminopterin, methotrexate, sulfasalazine, pyrimethamine, triamterene, and trimethoprim); group II—agents that affect other enzymes in folate metabolism, impair the absorption of folate, or increase the metabolic breakdown of folate (carbamazepine, phenytoin, primidone, and phenobarbital) (3). The case subjects were 3870 infants with cardiovascular defects, 1962 with oral clefts, and 1100 with urinary tract malformations. Infants with defects associated with a syndrome were excluded, as were infants with coexisting neural tube defects (NTDs; known to be reduced by maternal folic acid supplementation). Too few infants with limb reduction defects were identified to be analyzed. Controls (N = 8387) were infants with malformations other than oral clefts and cardiovascular, urinary tract, and limb reduction defects, and NTDs, but included infants with chromosomal and genetic defects. The risk of malformations in control infants would not have been reduced by vitamin supplementation, and none of the controls used folic acid antagonists (3). For group I cases, the relative risks (RRs) of cardiovascular defects and oral clefts were 3.4 (95% confidence interval [CI] 1.8–6.4) and 2.6 (95% CI 1.1–6.1), respectively. For group II cases, the RRs of cardiovascular and urinary tract defects, and oral clefts were 2.2 (95% CI 1.4–3.5), 2.5 (95% CI 1.2–5.0), and 2.5 (95% CI 1.5–4.2), respectively. Maternal use of multivitamin supplements with folic acid (typically 0.4 mg) reduced the risks in group I cases, but not in group II cases (6).
BREASTFEEDING SUMMARY
No reports describing the use of triamterene during lactation have been located. The molecular weight (about 253) is low enough that excretion into breast milk should be expected. The effect of this exposure on a nursing infant is unknown.
References
1.Pitkin RM, Kaminetzky HA, Newton M, Pritchard JA. Maternal nutrition: a selective review of clinical topics. Obstet Gynecol 1972;40:773–85.
2.Lindheimer MD, Katz AI. Sodium and diuretics in pregnancy. N Engl J Med 1973;288:891–4.
3.Christianson R, Page EW. Diuretic drugs and pregnancy. Obstet Gynecol 1976;48:647–52.
4.Product information. Dyrenium. WellSpring Pharmaceuticals, 2001.
5.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
6.Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608–14.