How often should liver enzymes, such as alanine transaminase (ALT) and aspartate transaminase (AST), be measured in individuals on long-term oral Lamisil (terbinafine)?

Liver Enzyme Monitoring for Long-Term Oral Lamisil (Terbinafine) Therapy

Liver function tests should be performed before starting terbinafine therapy, but routine monitoring during treatment is not recommended as it does not effectively identify cases of drug-induced liver injury before symptoms appear. 1, 2

FDA Recommendations and Rationale

• The FDA drug label for terbinafine states that liver function tests should be performed before prescribing terbinafine tablets since hepatotoxicity may occur in patients with and without pre-existing liver disease 1
• Cases of liver failure, some leading to liver transplant or death, have occurred with the use of terbinafine tablets in individuals with and without pre-existing liver disease 1
• Terbinafine is not recommended for patients with chronic or active liver disease 1

Evidence Against Routine Monitoring

• A critical review of terbinafine-induced severe liver injury found that no asymptomatic patients were identified through laboratory screening 2
• In this review of 69 symptomatic patients with terbinafine-induced liver injury, patients experienced symptoms for a mean of 14.8 days before seeking medical attention 2
• The mean duration of terbinafine treatment until onset of symptoms was 30.2 days (range 5-84 days), making it difficult to establish an optimal monitoring schedule 2
• The timeline of drug-induced liver injury onset varies significantly, with most cases occurring between 4 and 6 weeks after starting treatment 2

Patient Education and Symptom Monitoring

• Patients prescribed terbinafine should be warned to report immediately to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools 1
• The most common symptoms of terbinafine-induced liver injury in order of frequency are jaundice, flu-like symptoms, dark urine, and pruritus 2
• Patients who develop these symptoms should discontinue taking oral terbinafine immediately, and their liver function should be promptly evaluated 1

Special Populations Requiring Monitoring

• For patients with pre-existing liver disease or abnormal baseline liver function tests, periodic monitoring may be appropriate, though specific intervals are not established in guidelines 1
• Patients taking other hepatotoxic medications concurrently may benefit from more careful monitoring 1

Clinical Course of Terbinafine-Induced Liver Injury

• Terbinafine-induced liver injury typically presents as a mixed cholestatic-hepatocellular pattern 3, 4, 5
• The liver injury is likely caused by an idiosyncratic reaction rather than direct hepatotoxicity 5
• Recovery time varies, with some patients showing normalization of liver enzymes within 6 months after discontinuation 6, while others may have prolonged elevation of liver enzymes 4, 5

Conclusion

Based on the available evidence, particularly the FDA drug label and the critical review of terbinafine-induced liver injury, baseline liver function testing before starting terbinafine is recommended, but routine monitoring during treatment is not advised. Instead, patient education about symptoms of liver injury and prompt discontinuation of the medication if such symptoms occur is the most effective approach to managing the risk of hepatotoxicity.