Yeast Infections in Pregnancy: Recommended Treatments

Vaginal candidiasis, commonly called “yeast infection,” is relatively common during pregnancy, with an estimated prevalence of 10%-75%.[1,2] The patient usually presents with vulvar pruritus, burning, soreness, and irritation, with occasional dysuria.[3]

Pregnancy causes increased levels of progesterone and estrogen.[2] Progesterone suppresses the ability of neutrophils to combat Candida, and estrogen disrupts the integrity of vaginal epithelial cells against such pathogens as Candida and decreases immunoglobulins in vaginal secretions. These issues, which continue throughout pregnancy, lend themselves to multiple recurrences of infection.

Treatment is directed at symptom relief. Topical imidazoles are most commonly recommended. Although both miconazole and clotrimazole are available without a prescription, pregnant patients should never self-medicate and should only use these products under the direction of a healthcare provider.

Miconazole is classified by the US Food and Drug Administration (FDA) as pregnancy risk category C; however, the topical vaginal formulation achieves minimal systemic absorption. In clinical trials that included patients in the first trimester, no harm was demonstrated to the mother or fetus.[4]

Clotrimazole vaginal formulations are classified pregnancy risk category B. Studies in the second and third trimesters have not demonstrated adverse outcomes on the mother or fetus. Data are inadequate to categorize risk in the first trimester.[5]

Vaginal candidiasis is more difficult to eradicate during pregnancy, and prolonged durations of treatment ranging from 7 to 14 days are recommended. Multiple formulations and strengths of topical imidazoles are available that affect the duration of therapy for nonpregnant patients; however, during pregnancy, only the dosage forms designed for prolonged-duration therapy should be used.

Appropriate miconazole formulations include the 100-mg vaginal suppository or the 2% vaginal cream applied for a 7-day course of therapy. Clotrimazole 2% vaginal cream should be used for 7 days. Recurrent infections should be treated for 14 days.

Data in pregnancy for other topical antifungal agents are limited, making miconazole and clotrimazole the preferred topical agents in pregnancy.

Given its ease of use and excellent efficacy, oral fluconazole is commonly used for the treatment of vaginal candidiasis in nonpregnant patients. However, use of fluconazole in pregnancy has been controversial.

Animal data suggest that high-dose fluconazole is associated with craniofacial malformations.[6] An analysis of 1079 women from North Denmark who had a live birth or stillbirth after 20 weeks’ gestation found no association between short-term fluconazole use in the first trimester and congenital malformations.[7] However, results from a significantly larger Danish cohort suggested that patients who receive even low doses of fluconazole have a 48% greater risk for spontaneous abortion than those not exposed to fluconazole. Women who received fluconazole had a 62% greater risk for spontaneous abortion than women treated with topical azoles.[1] This study prompted the FDA to issue a safety alert for the prescribing of oral fluconazole during pregnancy.[8]

In summary, treatment of vaginal candidiasis in pregnancy should only be undertaken with guidance from a healthcare provider. Topical imidazoles (miconazole and clotrimazole) have the largest body of evidence regarding safety for both the mother and the fetus during pregnancy. Owing to the physiologic changes that occur during pregnancy that compromise host defenses against Candida, therapy should be continued for a total 7- to 14-day course.

Although fluconazole was previously considered safe in the dosages used to treat vaginal candidiasis, recently published data suggest a significantly higher incidence of miscarriage in patients who receive oral fluconazole for vaginal candidiasis compared with untreated patients and those treated with topical imidazoles. On the basis of these data, it would be prudent to avoid fluconazole during pregnancy if at all possible.

Reference:

1. Malgaard-Nielsen D, Svanstrom H, Melbye M, Hvlid A, Paternak B. Association between use of oral fluconazole during pregnancy and risk of spontaneous abortion and stillbirth. JAMA. 2016;315:58-67. Abstract

2.Aslam M, Hafeez R, Ijaz S, Thair M. Vulvovaginal candidiasis in pregnancy. Biomedica. 2008;24:54-56.

3. Sobel JD. Candida vulvovaginitis. UpToDate. http://www.uptodate.com/contents/candida-vulvovaginitis Accessed May 9, 2016.

4. Czeizel AE, Kazy Z, Puhó E. Population-based case-control teratologic study of topical miconazole. Congenit Anom (Kyoto). 2004;44:41-45. Abstract

5. Czeizel AE, Puhó EH, Kazy Z. The use of data set of the Hungarian case-control surveillance of congenital abnormalities for evaluation of birth outcomes beyond birth defects. Cent Eur J Public Health. 2007;15:147-153.Abstract

6. Menegola E, Broccia ML, Di Renzo F, Giavini E. Antifungal triazoles induce malformations in vitro. Reprod Toxicol. 2011;15:421-427.

7. Norgaard M, Pederson L, Gislum M, et al. Maternal use of fluconazole and risk of congenital malformations: a Danish population-based cohort study. J Antimicrob Chemother. 2008;62:172-176. Abstract

8. Fluconazole (Diflucan): Drug Safety Communication—FDA evaluating study examining use of oral fluconazole (Diflucan) in pregnancy.  http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm497656.htmAccessed May 9, 2016.

Response from Michael Postelnick, BPharm
Lecturer, Department of Medical Education, Northwestern University Feinberg School of Medicine; Senior Infectious Disease Pharmacist, Clinical Manager, Northwestern Memorial Hospital Department of Pharmacy, Chicago, Illinois

by Michael PharmD