Can a 39-year-old man who is hepatitis B surface antigen positive and taking Baraclude (entecavir) safely use oral terbinafine for severe toenail onychomycosis?

Terbinafine Use in HBsAg+ Patient on Entecavir

Terbinafine should be used with extreme caution in this patient, requiring mandatory baseline and ongoing liver function monitoring, but is not absolutely contraindicated if baseline liver enzymes are normal and the patient is virologically suppressed on entecavir. 1, 2

Critical Safety Considerations in Hepatitis B

The FDA explicitly warns that terbinafine should not be used in patients with underlying hepatic disease, and the manufacturer's labeling specifically recommends against use in patients with liver dysfunction. 2, 3 However, this must be distinguished from well-controlled chronic HBV infection:

• Active or chronic liver disease represents a contraindication to terbinafine, but chronic HBV infection that is virologically suppressed with normal transaminases does not automatically constitute "active liver disease." 1, 4
• A documented case report describes terbinafine-induced acute autoimmune hepatitis specifically in a patient with chronic HBV, suggesting this population may be at heightened risk for severe hepatotoxicity. 3
• The pathogenesis likely involves hapten-carrier complexes and cytochrome P450 isoenzymes, with the chronic HBV carrier state potentially predisposing to autoimmune reactions. 3

Pre-Treatment Requirements

Mandatory baseline testing must include:

• Liver function tests (ALT, AST, bilirubin) to document normal baseline values 5, 1, 6, 2
• Complete blood count due to rare hematologic effects 1, 6
• HBV DNA viral load to confirm virologic suppression on entecavir 3
• Serum transaminases are specifically required by FDA labeling before initiating therapy 2

Treatment Protocol if Proceeding

If baseline liver enzymes are normal and HBV is suppressed:

• Administer terbinafine 250 mg once daily for 12-16 weeks for severe toenail onychomycosis 5, 4
• Monitor liver function tests at 4-6 weeks after initiation, then monthly during treatment beyond one month 1, 7
• Continue entecavir throughout terbinafine therapy to prevent HBV reactivation 3

Monitoring and Discontinuation Criteria

Discontinue terbinafine immediately if:

• Any elevation in transaminases develops during therapy 1, 2
• Symptoms of hepatotoxicity appear: anorexia, nausea, fatigue, right upper quadrant pain, jaundice, dark urine, or pale stools 2, 3
• Peak liver enzyme elevations can occur 3 weeks after discontinuation, requiring continued monitoring 3

Alternative Treatment Options

Given the elevated risk profile, strongly consider alternatives:

• Itraconazole 200 mg daily for 12 weeks continuously or pulse therapy (400 mg daily for 1 week per month × 3 pulses) carries similar hepatotoxicity risk but may be preferred if there are concerns about terbinafine specifically 5, 1
• Topical therapy alone with amorolfine 5% lacquer once or twice weekly for 6-12 months or ciclopirox 8% lacquer daily for up to 48 weeks is the safest option, though less effective for severe disease 1, 4

Clinical Decision Algorithm

1. Confirm HBV suppression: Check HBV DNA viral load and ensure normal ALT/AST on current entecavir regimen 3
2. If suppressed with normal LFTs: Terbinafine can be used with intensive monitoring 1, 4
3. If any baseline transaminase elevation: Consider topical therapy or itraconazole instead 1, 4
4. If severe/extensive disease requiring systemic therapy: Terbinafine remains first-line for dermatophyte onychomycosis, but patient must understand elevated hepatotoxicity risk 5, 3

Critical Pitfalls to Avoid

• Do not assume chronic HBV automatically precludes terbinafine use—the distinction is between controlled infection versus active liver disease 1, 4
• Do not rely on baseline testing alone—ongoing monitoring is essential as hepatotoxicity can develop weeks into treatment 3, 7
• Do not attribute symptoms to the fungal infection—any constitutional symptoms during treatment warrant immediate liver function assessment 2, 3
• Ensure entecavir is continued throughout—stopping antiviral therapy could precipitate HBV flare, which would be difficult to distinguish from terbinafine hepatotoxicity 3