Are luliconazole and terbinafine (antifungal medications) safe to use during pregnancy?

Safety of Luliconazole and Terbinafine in Pregnancy

Neither luliconazole nor terbinafine should be used during pregnancy, as fungal nail and skin infections pose no risk to maternal or fetal health and can safely be deferred until after delivery.

Terbinafine in Pregnancy

FDA Classification and Recommendations

• The FDA drug label explicitly states: "It is not known if terbinafine will harm your unborn baby. You should not start using terbinafine during pregnancy without talking with your doctor" 1
• Terbinafine should be avoided during pregnancy because onychomycosis and dermatophyte infections are not life-threatening and pose no risk to maternal or fetal health if left untreated 2

Clinical Rationale for Avoidance

• Treatment can be safely postponed until after delivery, as these infections do not threaten pregnancy outcomes 2
• The optimal clinical effect occurs months after treatment completion due to the time required for healthy nail outgrowth, making treatment during pregnancy unnecessary 1
• While animal studies showed no adverse developmental effects at doses up to 3 times the maximum recommended human dose, human pregnancy data remain limited 1

Alternative Approaches

• For superficial fungal infections (not onychomycosis), topical antifungals are strongly preferred over any systemic therapy 2
• Topical agents such as clotrimazole, miconazole, and nystatin are considered first-line for superficial infections during pregnancy 3
• Topical terbinafine may be used cautiously after first-line topical agents, though data are limited 3

Luliconazole in Pregnancy

FDA Classification and Available Data

• There are no available data on luliconazole use in pregnant women to inform drug-associated risks for major birth defects and miscarriage 4
• Animal reproduction studies showed no adverse developmental effects in rats and rabbits at doses up to 3 and 24 times the maximum recommended human dose, respectively 4
• The estimated background risk of major birth defects in the U.S. general population is 2-4%, and miscarriage is 15-20% 4

Topical Application Considerations

• Luliconazole is a topical cream with limited systemic absorption 4
• Despite topical application, the complete absence of human pregnancy data makes its use inadvisable when safer alternatives exist 4
• Topical azoles with more established safety profiles (clotrimazole, miconazole) should be used instead 3, 5

Critical Distinction: Systemic vs. Topical Azoles

Systemic Azoles Are Contraindicated

• Systemically absorbed azoles should not be initiated during pregnancy and should be discontinued if pregnancy occurs 6
• High-dose fluconazole (≥400 mg/day) is associated with a specific syndrome of birth defects including craniosynostosis, characteristic facies, digital synostosis, and limb contractures ("fluconazole embryopathy") 6, 2
• Itraconazole is explicitly contraindicated in pregnancy due to embryotoxicity and teratogenicity in animal studies 6, 2

Topical Azoles Are Generally Safe

• Topical imidazoles (clotrimazole, miconazole) are considered safe and are first-line agents for superficial fungal infections during pregnancy 3, 5
• Topical therapy is preferred when possible for oral or vaginal candidiasis 6
• Nystatin is minimally absorbed and effective for vaginal therapy 5

When Systemic Antifungal Therapy Is Absolutely Necessary

Life-Threatening Infections Only

• If systemic therapy is required for life-threatening fungal infection, amphotericin B is the drug of choice 2, 7, 5, 8
• Amphotericin B has the most extensive safety data in pregnancy with no reports of teratogenesis 7, 5
• Neonates born to women on chronic amphotericin B at delivery should be evaluated for renal dysfunction and hypokalemia 6

Common Pitfalls to Avoid

Do Not Treat Non-Urgent Infections

• The most common error is treating onychomycosis or superficial dermatophyte infections during pregnancy when deferral poses no risk 2
• These conditions can wait until after delivery and breastfeeding are complete 2

Do Not Confuse Topical with Systemic Safety

• Topical azoles have established safety profiles that do not apply to systemic azoles 3, 5
• Even topical preparations can have higher systemic absorption when applied to mucous membranes compared to intact skin 5

Consider Pregnancy Testing

• Women of childbearing age on systemic antifungals should use effective contraception 6
• If pregnancy occurs during systemic azole therapy, the medication should be discontinued immediately 6