METHENAMINE

Fetal Risk Summary

Methenamine, in either the mandelate or hippurate salt form, is used for chronic suppressive treatment of bacteriuria. In two studies, the mandelate form was given to 120 patients and the hippurate to 70 patients (1,2). No increases in congenital defects or other problems as compared with controls were observed.

The Collaborative Perinatal Project reported 49 1st trimester exposures to methenamine (3, pp. 299, 302). For use anytime in pregnancy, 299 exposures were recorded (3, p. 435). Only in the latter group was a possible association with malformations found. Independent confirmation is required.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 209 newborns had been exposed to methenamine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Eight (3.8%) major birth defects were observed (nine expected). Specific data were available for six defect categories, including (observed/expected) 1/2 cardiovascular defects, 1/0.5 oral clefts, 0/0 spina bifida, 1/1 polydactyly, 1/0.5 limb reduction defects, and 0/0.5 hypospadias. These data do not support an association between the drug and congenital defects.

Methenamine interferes with the determination of urinary estrogen (4). Urinary estrogen was formerly used to assess the condition of the fetoplacental unit, depressed levels being associated with fetal distress. This assessment is now made by measuring unconjugated estriol, which is not affected by methenamine.

Breast Feeding Summary

Methenamine is excreted into breast milk. Peak levels occur at 1 hour (5). No adverse effects on the nursing infant have been reported.

References

1. Gordon SF. Asymptomatic bacteriuria of pregnancy. Clin Med 1972;79:22–4.
2. Furness ET, McDonald PJ, Beasley NV. Urinary antiseptics in asymptomatic bacteriuria of pregnancy. NZ Med J 1975;81:417–9.
3. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
4. Kivinen S, Tuimala R. Decreased urinary oestriol concentrations in pregnant women during hexamine hippurate treatment. Br Med J 1977;2:682.
5. Sapeika N. The excretion of drugs in human milk—a review. J Obstet Gynaecol Br Emp 1947;54:426–31.