Is Jublia (Efinaconazole) Safe in Pregnancy?
Jublia (efinaconazole 10% topical solution) has no available human pregnancy data, but animal studies show no malformations at exposures 112-154 times the human dose, and systemic absorption after topical application is minimal, making it a reasonable option when treating onychomycosis during pregnancy is clinically necessary. 1
FDA Pregnancy Classification and Animal Data
The FDA label for Jublia states there are no available human data for use during pregnancy to inform drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 1
Animal reproduction studies in pregnant rabbits and rats showed efinaconazole did not cause malformations or fetal harm when administered subcutaneously during organogenesis at doses up to 112 times (rats) and 154 times (rabbits) the Maximum Recommended Human Dose (MRHD) based on AUC comparisons. 1
Embryolethality occurred only in rats at 559 times the MRHD in the presence of maternal toxicity—far exceeding any clinically relevant exposure. 1
In perinatal/postnatal rat studies, no developmental effects occurred at exposures 17 times the MRHD, and no effects on postnatal development were noted at 89 times the MRHD. 1, 2
Systemic Absorption Considerations
Efinaconazole is applied topically to toenails, and pharmacokinetic studies demonstrate minimal systemic absorption, which substantially reduces theoretical fetal exposure compared to oral azole antifungals. 1, 3
The drug's mechanism relies on local nail penetration due to low surface tension, poor water solubility, and low keratin affinity—properties that enhance topical efficacy while limiting systemic distribution. 3
Context: Azole Antifungals in Pregnancy
High-dose oral azoles (particularly fluconazole 400-800 mg/day) during the first trimester are associated with a specific pattern of birth defects including craniosynostosis, characteristic facies, digital synostosis, and limb contractures ("fluconazole embryopathy"). 4, 5
Topical azoles are preferred over systemic azoles throughout pregnancy when treating superficial fungal infections. 4, 6
For serious systemic fungal infections requiring treatment during pregnancy, intravenous amphotericin B is the preferred agent, particularly in the first trimester. 4, 6, 5
Clinical Decision-Making for Jublia in Pregnancy
Onychomycosis is not a life-threatening condition, and deferring treatment until after delivery is a reasonable approach for most pregnant patients. 4
If treatment during pregnancy is deemed necessary (e.g., significant pain, secondary bacterial infection, or quality of life concerns), Jublia's topical application with minimal systemic absorption makes it a more favorable option than oral antifungals. 1, 3
The British Association of Dermatologists notes that topical antifungals like amorolfine have rare side effects limited to local burning, pruritus, and erythema—a safety profile likely similar to efinaconazole. 4
Important Caveats
The background risk of major birth defects in the U.S. general population is 2-4%, and miscarriage is 15-20% of clinically recognized pregnancies—context essential for counseling patients. 1
Women of childbearing potential using systemic azoles should employ effective contraception, though this concern is substantially reduced with topical efinaconazole given minimal absorption. 4, 5
No postmarketing surveillance data exist for Jublia use during human pregnancy, so theoretical risks cannot be completely excluded. 1
Lactation Considerations
It is unknown whether efinaconazole is excreted in human breast milk, though it was detected in milk of nursing rats after subcutaneous administration. 1
Given the minimal systemic absorption from topical toenail application, breastfeeding while using Jublia is likely low risk, though caution is advised per the FDA label. 1