Terbinafine Safety in Pregnancy and Hepatic Hemangiomas
Terbinafine is classified as FDA pregnancy category B and can be considered safe for use during pregnancy, with no increased risk of major malformations or spontaneous abortion, though it should be avoided unless benefits clearly outweigh risks; terbinafine does NOT cause hepatic hemangiomas.
Pregnancy Safety
Evidence from Guidelines and Research
The most recent and highest-quality evidence comes from a 2020 Danish nationwide registry study of 1,650,649 pregnancies 1. This large cohort study found no increased risk of major malformations (prevalence 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 during pregnancy. A 2022 systematic review corroborated these findings, concluding that both systemic and topical terbinafine can be regarded as safe during pregnancy 2.
However, guideline recommendations remain more conservative. The 2007 IDSA sporotrichosis guidelines note that terbinafine is FDA pregnancy category B, meaning it is not expected to harm an unborn baby 3. The guideline states that pregnant patients and nursing mothers should discuss risks and benefits with their physicians, acknowledging that terbinafine passes into breast milk 3.
Clinical Decision-Making Algorithm
- For non-life-threatening fungal infections: Delay treatment until after pregnancy completion, as fungal nail infections do not worsen with pregnancy and pose no risk to the fetus 3
- For cutaneous/lymphocutaneous infections requiring treatment: Consider local hyperthermia as an alternative 3
- If treatment cannot be delayed: Terbinafine may be used after careful risk-benefit discussion, given the robust safety data from recent large studies 2, 1
- For life-threatening systemic infections: Use amphotericin B, which can be safely administered during pregnancy 3
Important Caveats
While recent research is reassuring, azole antifungals (itraconazole, fluconazole) are contraindicated in pregnancy due to teratogenic potential 4, 3. This makes terbinafine a potentially safer alternative when antifungal treatment is necessary. The drug does pass into breast milk, requiring discussion about breastfeeding 3.
Hepatic Hemangiomas
There is absolutely no evidence that terbinafine causes hepatic hemangiomas. This concern appears to be unfounded based on available literature.
What the Evidence Shows
The FDA drug label for terbinafine documents that in a 28-month rat carcinogenicity study, an increase in liver tumors was observed at high doses (2x the maximum recommended human dose) 5. However, these were hepatic tumors in rats, not hemangiomas, and occurred only at supratherapeutic doses.
Hepatic hemangiomas are benign vascular malformations and the most common benign liver tumors 6, 7. They are not drug-induced lesions. The 2023 EASL pregnancy guidelines specifically address hepatic hemangiomas in the context of pregnancy, noting that women with hemangiomas should be advised they do not preclude pregnancy 8. The guideline recommends imaging surveillance during each trimester only for large or exophytic hemangiomas at higher risk of rupture 8.
Actual Hepatotoxicity Concerns with Terbinafine
The real hepatic concern with terbinafine is idiosyncratic drug-induced liver injury (DILI), not hemangioma formation. The 2014 British Association of Dermatologists guidelines note that while terbinafine is associated with minimal hepatic toxicity, rare cases of serious hepatotoxicity have occurred, usually in patients with pre-existing liver disease 9.
Baseline liver function tests and complete blood count are recommended before starting terbinafine in patients with:
- History of heavy alcohol consumption
- Hepatitis
- Haematological abnormalities
- Pre-existing liver disease 9
The FDA label documents rare cases of liver failure leading to death or liver transplant 5. A 2024 case report describes terbinafine-induced cholestatic liver injury with marked cholestasis and bile granulomas 10. Systemic terbinafine is not recommended in patients with active or chronic liver disease 9.
Common Side Effects
The most frequent adverse events are gastrointestinal (49%): nausea, diarrhea, taste disturbance; and dermatological (23%): rash, pruritus, urticaria 9. Taste disturbance occurs in approximately 1:400 patients and can rarely be permanent 4, 9. Patients must be warned of this risk before starting therapy.