Is it safe to start Terbinafine (Lamisil) with mildly elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels?

From the Guidelines

Terbinafine can be safely initiated in patients with low AST and ALT levels, but monitoring liver function is recommended. Before starting treatment, obtain baseline liver function tests. For typical adult dosing, prescribe 250 mg of oral terbinafine once daily for 6 weeks for fingernail infections or 12 weeks for toenail infections. During treatment, repeat liver function tests at 4-6 weeks and if any symptoms of liver dysfunction develop (such as fatigue, nausea, right upper quadrant pain, dark urine, or jaundice).

Key Considerations

• Terbinafine should be discontinued if AST/ALT levels rise to greater than 3 times the upper limit of normal or if symptoms of liver injury develop, as suggested by 1.
• The mechanism of liver injury appears to be idiosyncratic and not directly related to baseline liver function, as noted in 1.
• Most patients with normal or slightly abnormal baseline liver enzymes can safely complete the full course of therapy with appropriate monitoring.

Monitoring and Management

• Repeat liver function tests at 4-6 weeks and if any symptoms of liver dysfunction develop.
• Discontinue terbinafine if AST/ALT levels rise to greater than 3 times the upper limit of normal or if symptoms of liver injury develop.
• Consider alternative treatments if terbinafine is discontinued due to liver injury.

Important Notes

• Terbinafine can rarely cause hepatotoxicity, with an estimated incidence of serious liver injury of approximately 1 in 50,000 to 120,000 patients, as mentioned in 1.
• The British Association of Dermatologists' guidelines for the management of onychomycosis recommend baseline liver function tests and monitoring during treatment with terbinafine, as stated in 1.

From the FDA Drug Label

Measurement of serum transaminases (ALT and AST) is advised for all patients before taking terbinafine tablets

• Low AST and ALT values are not a contraindication to starting terbinafine, but rather an indication that liver function tests have been performed as recommended.
• It is recommended to start terbinafine as long as liver function tests, including AST and ALT, have been evaluated and found to be acceptable by the physician.
• Periodic monitoring of liver function tests is recommended during terbinafine treatment to detect any potential hepatotoxicity 2.

From the Research

Starting Terbinafine with Low AST, ALT

• Terbinafine is an orally active antimycotic agent that inhibits the biosynthesis of ergosterol in fungi, resulting in a fungistatic and fungicidal effect 3.
• The efficacy and safety of terbinafine in dermatophyte toenail onychomycosis in adults has been established in many studies, with a meta-average for mycological cure of 76% +/- 3% (mean +/- standard error) 4.
• Terbinafine has been reported to be superior to both itraconazole and fluconazole in comparative studies in the treatment of dermatophyte toenail onychomycosis 4.
• A retrospective analysis of liver enzyme abnormalities in patients prescribed terbinafine and itraconazole for onychomycosis found that the proportion of patients with elevated aspartate transaminase (AST) levels was 5.2% for terbinafine and 0% for itraconazole at the end of the first month 5.
• The same study found that 8.4% of patients with terbinafine had elevated alanine aminotransferase (ALT) levels, and 7.5% of patients who were on itraconazole treatment had high ALT levels 5.
• It is recommended to monitor liver function tests prior to the administration of any oral antifungals, especially when clinically indicated, due to the potential risk of hepatotoxicity 6.
• A meta-analysis of the safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis found that the pooled risks of treatment discontinuation resulting from adverse reactions for continuous therapy were 3.44% for terbinafine 250 mg/day 7.
• The risk of liver injury requiring termination of treatment ranged from 0.11% to 1.22% for all treatment regimens evaluated, and the risk of having asymptomatic elevation of serum transaminase but not requiring treatment discontinuation was less than 2.0% for all treatment regimens evaluated 7.

Considerations for Starting Terbinafine

• Baseline and regular laboratory monitoring for AST and ALT should be done to monitor liver toxicity with terbinafine 5.
• Terbinafine has a low potential for drug-drug interactions, but it is still important to consider potential interactions with other medications 3.
• The diagnosis of onychomycosis should be confirmed, and consideration given to antifungal susceptibility testing in the event of a first treatment failure 6.