What are the implications of elevated alkaline phosphatase (alk/phos) on oral terbinafine (terbinafine) therapy for toenail fungus?

From the Guidelines

Given the elevated alkaline phosphatase in your patient needing treatment for toenail fungus, you should avoid oral terbinafine due to its potential for hepatotoxicity, especially in patients with pre-existing liver disease, as noted in the British Association of Dermatologists' guidelines for the management of onychomycosis 2014 1. When considering treatment options for toenail fungus, it's essential to weigh the risks and benefits, particularly in patients with abnormal liver function. The guidelines suggest that systemic terbinafine is not recommended in patients with active or chronic liver disease, and baseline liver function tests are recommended in patients with a history of heavy alcohol consumption, hepatitis, or haematological abnormalities 1. Some key points to consider when treating toenail fungus in patients with elevated liver enzymes include:

• Topical antifungals like ciclopirox 8% nail lacquer or efinaconazole 10% solution may be reasonable alternatives to oral terbinafine
• If oral therapy is strongly preferred, consider fluconazole 150-300mg once weekly for 6-12 months, which may have less hepatotoxic potential
• Comprehensive liver function tests, including ALT, AST, bilirubin, and albumin, should be obtained before initiating any oral antifungal to better assess hepatic function
• For patients with mild liver function abnormalities who still require oral terbinafine, a reduced dose (such as 250mg every other day) with monthly liver function monitoring throughout treatment may be considered
• Regardless of treatment choice, follow-up liver function tests should be performed to monitor the elevated alkaline phosphatase, as terbinafine has been associated with rare reports of serious hepatic toxicity, particularly in patients with pre-existing liver disease 1.

From the FDA Drug Label

1. 1 Hepatotoxicity 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. ... Terbinafine tablets are not recommended for patients with chronic or active liver disease Before prescribing terbinafine tablets, liver function tests should be performed since hepatotoxicity may occur in patients with and without pre-existing liver disease. Periodic monitoring of liver function tests is recommended. Terbinafine tablets should be immediately discontinued in case of elevation of liver function tests

The patient has elevated alk/phos, which is a liver function test. Given this information, terbinafine tablets should be immediately discontinued or not initiated due to the risk of hepatotoxicity. The FDA label recommends against using terbinafine in patients with chronic or active liver disease and advises periodic monitoring of liver function tests. In this case, since the patient's liver function test is already elevated, it is best to avoid using terbinafine tablets 2.

From the Research

Patient with Elevated Alk/Phos and Toenail Fungus

• The patient has been prescribed oral terbinafine for toenail fungus, but has elevated hepatic function alk/phos levels.
• According to the study 3, terbinafine was used by 433 patients (76.4%) for one month, and at the end of the first month, the proportion of patients with elevated aspartate transaminase (AST) levels was 5.2% for terbinafine.
• The study 4 recommends laboratory testing of liver function tests prior to the administration of any oral antifungals, especially when clinically indicated.
• Another study 5 states that the risk of terbinafine-induced hepatotoxicity is negligible in healthy patients, but systemic antifungals are limited by risks of systemic toxicity and drug-drug interactions.

Monitoring and Treatment

• The study 3 suggests that baseline and regular laboratory monitoring for AST and ALT should be done to monitor liver toxicity with terbinafine.
• The study 6 mentions that oral terbinafine is the treatment of choice for onychomycosis, followed by oral itraconazole.
• The study 7 discusses the pathophysiology of alkaline phosphatase and the mechanisms involved in the homeostasis of this enzyme, including the concept of defective enzyme elimination.

Considerations

• The patient's elevated alk/phos levels should be taken into consideration when prescribing oral terbinafine, and regular monitoring of liver function tests is recommended 4, 5.
• The study 5 also mentions that a detailed medication history is critical before prescribing systemic antifungals due to the risk of drug-drug interactions.
• The patient's treatment plan should be individualized, taking into account the severity of the disease, comorbidities, and patient characteristics 6.