What are the effects of oral Terbinafine (Lamisil) on the liver?

From the Guidelines

Oral terbinafine is not recommended in patients with active or chronic liver disease due to the risk of serious hepatic toxicity, as evidenced by studies such as 1. When considering the use of oral terbinafine, it is crucial to assess the patient's liver function beforehand, especially in those with a history of heavy alcohol consumption, hepatitis, or hematological abnormalities. Baseline liver function tests and a complete full blood count are recommended for these patients, as well as for children, given that terbinafine is not licensed for pediatric use 1. The risk of liver damage, although rare, necessitates careful monitoring and immediate cessation of the medication if symptoms such as fatigue, nausea, vomiting, abdominal pain, dark urine, or jaundice appear. Terbinafine's effectiveness in treating fungal nail and skin infections must be weighed against the potential for hepatotoxicity, particularly in vulnerable populations. Given the information from 1 and 1, the standard treatment course for oral terbinafine is typically 6 weeks for fingernail infections and 12 weeks for toenail infections, with careful consideration of the patient's overall health status and potential risks. Key points to consider include:

• Pre-existing liver disease increases the risk of hepatotoxicity
• Baseline liver function tests are recommended for at-risk patients
• Monitoring for signs of liver issues is crucial during treatment
• Terbinafine remains an effective treatment option when used judiciously under medical supervision, as outlined in guidelines such as those from the British Association of Dermatologists 1.

From the FDA Drug Label

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. The severity of hepatic events and/or their outcome may be worse in patients with active or chronic liver disease. Treatment with terbinafine tablets should be discontinued if biochemical or clinical evidence of liver injury develops. 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 Patients prescribed terbinafine tablets 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. Patients with these symptoms should discontinue taking oral terbinafine, and the patient’s liver function should be immediately evaluated.

Oral terbinafine can cause liver damage. The FDA drug label warns of cases of liver failure, some leading to liver transplant or death, in individuals with and without pre-existing liver disease.

• Liver function tests should be performed before prescribing terbinafine.
• Periodic monitoring of liver function tests is recommended.
• Terbinafine should be discontinued if biochemical or clinical evidence of liver injury develops.
• Patients should be warned to report any symptoms of liver damage, such as nausea, anorexia, fatigue, vomiting, right upper abdominal pain, or jaundice, and to discontinue taking oral terbinafine if these symptoms occur 2.

From the Research

Oral Terbinafine and Liver Disease

• Oral terbinafine is often considered contraindicated in those with liver disease due to its known side effect of hepatotoxicity 3.
• However, a case study reported the safe use of oral terbinafine in a patient with stable autoimmune hepatitis, with precautions taken to minimize the risk of worsening hepatotoxicity 3.
• The patient's fungal infection cleared without any signs or symptoms of worsening liver disease, and the rash had not recurred 6 months after treatment 3.

Symptoms of Terbinafine-Induced Liver Injury

• Symptoms of terbinafine-induced severe liver injury include jaundice, flu-like symptoms, dark urine, and pruritus 4.
• Patients who experience liver injury due to terbinafine are usually symptomatic, and no asymptomatic patients were identified through laboratory screening 4.
• The timeline of liver injury onset varies significantly, but most cases occur between 4 and 6 weeks after starting treatment 4.

Monitoring Liver Function

• Some studies recommend monitoring liver function tests during terbinafine therapy, especially in patients with pre-existing liver disease 5, 6.
• However, another study suggests that monitoring liver function tests may not be meaningful, and patients should be advised to discontinue treatment and seek medical attention if symptoms of liver injury occur 4.
• Baseline and regular laboratory monitoring for liver enzymes such as AST and ALT should be done to monitor liver toxicity with terbinafine and itraconazole 6.

Hepatotoxicity Associated with Antifungal Agents

• Antifungal agents, including terbinafine, may cause hepatic toxicity ranging from mild and asymptomatic abnormalities in liver function tests to substantial liver injury and fulminant hepatic failure 7.
• A thorough understanding of the distribution, metabolism, elimination, and drug-drug interactions of antifungal agents is necessary to guide their safe use in patients at high risk for the development of hepatic dysfunction 7.