Is Terbinafine (oral antifungal) safe to use during the second trimester of pregnancy?

Oral Terbinafine Should Not Be Used During the Second Trimester of Pregnancy

Terbinafine is classified as FDA Pregnancy Category B, and the FDA drug label explicitly recommends that "treatment of onychomycosis can be postponed until after pregnancy is completed" and that "it is recommended that terbinafine not be initiated during pregnancy." 1

FDA Drug Label Guidance

The official FDA labeling for terbinafine provides clear direction:

• Animal reproduction studies at doses up to 12-23 times the maximum recommended human dose showed no evidence of impaired fertility or fetal harm 1
• However, there are no adequate and well-controlled studies in pregnant women, and because animal studies are not always predictive of human response, terbinafine should not be initiated during pregnancy 1
• The fundamental recommendation is that fungal nail infections can and should be postponed until after pregnancy is completed 1

Clinical Context: Why Treatment Can Be Delayed

The rationale for avoiding terbinafine during pregnancy is straightforward:

• Onychomycosis and most dermatophyte infections are not life-threatening conditions and pose no risk to maternal or fetal health if left untreated during pregnancy 2
• Treatment outcomes are not compromised by delaying therapy until after delivery 1
• The optimal clinical effect of terbinafine occurs months after treatment completion due to the time required for healthy nail outgrowth, making pregnancy an inappropriate time to initiate therapy 1

Alternative Approaches During Pregnancy

If antifungal treatment is deemed absolutely necessary during pregnancy:

• For superficial fungal infections (not onychomycosis), topical antifungals are preferred 3, 4
• Topical clotrimazole, miconazole, and nystatin are considered first-line agents during pregnancy 4
• Topical terbinafine may be used after the first trimester if other agents fail, as topical formulations have limited systemic absorption 4
• For candidal intertrigo, local nystatin or azole preparations are recommended 3

Recent Safety Data: Important Nuance

While the FDA label remains conservative, recent high-quality research provides reassuring data:

• A 2020 Danish nationwide cohort study of 1,650,649 pregnancies found no increased risk of major malformations (OR 1.01,95% CI 0.63-1.62) or spontaneous abortion (HR 1.06,95% CI 0.86-1.32) with oral terbinafine exposure 5
• A 2022 systematic review concluded that terbinafine use during pregnancy can be regarded as safe, with no increased risk of congenital malformations, spontaneous abortion, preterm birth, or stillbirth 6
• A 2017 review classified terbinafine as likely safe during pregnancy, though recommended as a second-line agent 4

Clinical Decision Algorithm

Despite emerging safety data, the current standard of care remains:

1. Postpone all treatment of onychomycosis until after pregnancy 1
2. If superficial fungal infection requires treatment, use topical agents first 3, 4
3. Avoid systemic azoles (itraconazole, fluconazole) during pregnancy due to established teratogenic risks 2, 7
4. If systemic therapy is absolutely necessary for life-threatening fungal infection, amphotericin B is the drug of choice 2

Critical Distinction from Other Antifungals

Terbinafine's safety profile differs significantly from azole antifungals:

• Itraconazole is explicitly contraindicated in pregnancy 2
• High-dose fluconazole (400-800 mg/day) during the first trimester is associated with birth defects including craniosynostosis and skeletal abnormalities 8, 7
• Terbinafine has no established teratogenic effects in humans, but lacks sufficient controlled studies to recommend use 1, 6, 5

Breastfeeding Considerations

Terbinafine is not recommended during breastfeeding:

• The drug is present in breast milk with a milk-to-plasma ratio of 7:1 1
• Treatment with terbinafine is not recommended in nursing mothers 1

Bottom Line for Clinical Practice

The answer to whether terbinafine can be used in the second trimester is definitively NO based on current FDA labeling and standard of care 1. While recent research suggests the drug may be safer than previously thought 6, 5, the lack of adequate controlled studies in pregnant women, combined with the non-urgent nature of onychomycosis, makes postponing treatment until after pregnancy the only appropriate recommendation 1.