What are the recommendations for using Terbinafine (antifungal medication) in patients with elevated Aspartate Aminotransferase (AST) levels?

Terbinafine Use with Elevated AST

Baseline liver function tests including AST and ALT must be obtained before prescribing terbinafine, and the drug should be immediately discontinued if AST elevations occur during treatment. 1

Pre-Treatment Requirements

All patients require baseline hepatic monitoring before starting terbinafine:

• Measure serum transaminases (ALT and AST) before prescribing terbinafine in every patient 1
• Obtain complete blood count alongside baseline liver function tests 2
• Terbinafine is contraindicated in patients with active or chronic liver disease 2

The FDA explicitly states that hepatotoxicity may occur in patients both with and without pre-existing liver disease, making baseline assessment mandatory regardless of risk factors. 1

Management Algorithm for Elevated AST

If AST is Elevated at Baseline:

• Do not initiate terbinafine 2, 1
• Consider alternative antifungal agents such as topical amorolfine 5% lacquer or ciclopirox 8% lacquer for onychomycosis 2
• If systemic therapy is essential and hepatic function normalizes, itraconazole may be considered as an alternative 2

If AST Elevates During Treatment:

• Immediately discontinue terbinafine 1
• Patients must stop treatment and have liver function evaluated immediately if they develop symptoms including persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools 1
• Do not restart terbinafine even after normalization, as hepatotoxicity can be severe and potentially lead to liver failure, transplant, or death 1

Monitoring During Treatment

For patients without baseline liver disease who start terbinafine:

• The British Association of Dermatologists recommends monitoring hepatic function tests during therapy, particularly if treatment extends beyond one month 2
• High-risk patients (history of heavy alcohol consumption, hepatitis, or hematological abnormalities) require baseline LFTs and closer monitoring 2

However, recent evidence suggests routine interval monitoring may be unnecessary in healthy patients. A large retrospective study of 4,985 patients found that AST elevations during terbinafine treatment were infrequent (comparable to baseline rates at 3.5% vs 3.6%) and most abnormalities were low-grade, not requiring medication discontinuation. 3

Clinical Context and Severity

The pattern of terbinafine hepatotoxicity is typically mixed cholestatic-hepatocellular:

• Median latency to onset is 38 days (range 24-114 days) 4
• 80% of affected patients present with jaundice 4
• Critically, 54% of patients had ongoing liver injury at 6 months, with persistent abnormalities in some cases at 24 months 4
• One patient in a case series required liver transplantation for acute liver failure 4

The hepatotoxicity appears to be idiosyncratic rather than dose-dependent, with strong genetic association to HLA-A*33:01 in Caucasian patients (91% of cases). 5, 4

Risk-Benefit Considerations

Given that terbinafine hepatotoxicity can be severe, prolonged, and potentially fatal, any elevation in AST—whether at baseline or during treatment—warrants immediate cessation and consideration of alternative therapies. 1, 4

Alternative treatment options include:

• Topical therapy with amorolfine 5% or ciclopirox 8% lacquer for onychomycosis (applied for 6-12 months) 2
• Itraconazole for systemic therapy if hepatic function is normal 2
• Griseofulvin, though less effective than terbinafine for dermatophyte infections 6, 7

Critical Warnings

• Terbinafine should never be restarted after hepatotoxicity develops, as the injury can be prolonged or permanent 4
• Patient education is essential: instruct all patients to immediately report any symptoms of liver injury and discontinue the medication 1
• The risk of chronic cholestatic injury persisting beyond treatment cessation makes prevention through proper screening and monitoring paramount 4