Clotrimazole

 Risk Factor: B
 Class: ANTI-INFECTIVES / Antifungals

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

No reports linking the use of clotrimazole with congenital defects have been located. The topical use of the drug in pregnancy has been studied (1,2,3 and 4). No adverse effects attributable to clotrimazole were observed. Absorption of the agent from the skin and vagina is minimal (5).

Suspected birth defect diagnoses occurred in 6,564 offspring of 104,339 women in a retrospective analysis of women who had delivered in Michigan hospitals during 19801983 (6). First trimester vaginitis treatment with clotrimazole occurred in 74 of the 6,564 deliveries linked to birth defect diagnoses and in 1,012 of the 97,775 cases not linked to such diagnoses. The estimated relative risk of birth defects when clotrimazole was used was 1.09 (95% confidence interval [CI] 0.91.4). Although an increased relative risk was not found, this study could not exclude the possibility of an association with a specific birth defect (6).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 2,624 newborns had been exposed to clotrimazole (maternal vaginal use) during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 118 (4.5%) major birth defects were observed (112 expected). Specific data were available for six defect categories, including (observed/expected) 27/26 cardiovascular defects, 4/4 oral clefts, 3/1 spina bifida, 9/7 polydactyly, 1/4 limb reduction defects, and 6/6 hypospadias. These data do not support an association between vaginal use of clotrimazole and congenital defects.

Data from the Hungarian Case-Control Surveillance of Congenital Abnormalities (19801992) were used to examine the potential teratogenic effects of vaginal and/or topical use of clotrimazole (7). Although clotrimazole use was not associated with an increase in the prevalence of any birth defect (fetal and live births), there was a suggestion that it was associated with a decrease in the prevalence of undescended testis (prevalence odds ratio 0.72, 95% confidence interval 0.540.95 (7).

Breast Feeding Summary

The absorption of clotrimazole from the skin and vagina is minimal (5). Therefore, it is doubtful if measurable amounts of the antifungal agent appear in milk.

References

1. Tan CG, Good CS, Milne LJR, Loudon JDO. A comparative trial of six day therapy with clotrimazole and nystatin in pregnant patients with vaginal candidiasis. Postgrad Med 1974;50(Suppl 1): 1025.
2. Frerich W, Gad A. The frequency of Candida infections in pregnancy and their treatment with clotrimazole. Curr Med Res Opin 1977;4:6404.
3. Haram K, Digranes A. Vulvovaginal candidiasis in pregnancy treated with clotrimazole. Acta Obstet Gynecol Scand 1978;57:4535.
4. Svendsen E, Lie S, Gunderson TH, Lyngstad-Vik I, Skuland J. Comparative evaluation of miconazole, clotrimazole and nystatin in the treatment of candidal vulvo-vaginitis. Curr Ther Res 1978;23: 66672.
5. Product information. Lotrimin. Schering, 2000.
6. Rosa FW, Baum C, Shaw M. Pregnancy outcomes after first-trimester vaginitis drug therapy. Obstet Gynecol 1987;69:7515.
7. Czeizel AE, Toth M, Rockenbauer M. No teratogenic effect after clotrimazole therapy during pregnancy. Epidemiology 1999;10:43740.