Fluconazole During Pregnancy – Is It Safe?

June 16, 2020

Written by Clay Smith

Spoon Feed
Even at the usual low dose for vulvovaginal candidiasis, fluconazole was associated with an increased risk of musculoskeletal (MSK) malformations when given in the first trimester. Higher doses were associated with an even greater risk.

Why does this matter?
Vaginal candidiasis is common in pregnancy.  Oral fluconazole 150mg once is a non-messy treatment option, as opposed to topical azoles.  In 2016, JAMA published an article that found increased risk of stillbirth and miscarriage in women who received fluconazole.  Then, a larger study in JAMA Internal Medicine was reassuring. Case reports described a unique phenotype of malformations attributed to fluconazole. And in 2011, the FDA issued a warning about high dose fluconazole in pregnancy. Is lower dose fluconazole safe?

Probably not best
This was a large, national, public insurance database study comparing women who received oral fluconazole (N = 37,650) for vulvovaginal candidiasis in the first trimester vs. those who received topical azoles (82,090). There was no increase in cardiac conotruncal malformations (propensity score matching RR 1.04, 95%CI 0.70 to 1.55) or oral clefts (RR 0.91, 95%CI 0.61 to 1.35) associated with fluconazole use. However, when considering all MSK malformations together (skull, face, jaw, feet, or spine), there was an increased risk with fluconazole with propensity score matching (1.30, 95%CI 1.09 to 1.56) compared to the topical azole group. There was also greater risk with a higher dose of fluconazole >450mg (RR 2.29, 95%CI 1.43 to 3.68).

Source
Oral Fluconazole Use in the First Trimester and Risk of Congenital Malformations: Population Based Cohort Study. BMJ. 2020 May 20;369:m1494. doi: 10.1136/bmj.m1494.

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