Terbinafine

Oral therapy with terbinafine is a well-known cause of acute liver injury that can be severe and even fatal. In addition, terbinafine therapy is associated with transient elevations in serum aminotransferases, occurring in less than 1% of patients which are generally asymptomatic and short-lived even without stopping therapy. The estimated probability of developing elevated serum aminotransferase levels requiring stopping treatment is about 0.3% for 2 to 6 weeks of treatment and 0.4% for treatment longer than 8 weeks.；Clinically apparent liver injury from terbinafine is rare (1 in 2,500 to 1:25,000 persons exposed), but many case reports and even case series have been described in the literature. Liver injury usually arises within the first 6 weeks of therapy. The pattern of injury can be either hepatocellular or mixed initially but it typically evolves into a cholestatic pattern which can be prolonged (Cases 1 and 2). Some cases may progress to vanishing bile duct syndrome. Signs of hypersensitivity (rash, fever, eosinophilia) are not common and, when present, are generally mild-to-moderate in severity. Autoantibody formation is rare. In addition, cases with severe hepatocellular injury with acute liver failure have been described. These instances are marked by precipitous onset with marked elevations in serum aminotransferase levels and progressive jaundice and hepatic failure. Terbinafine has also been implicated in cases of Stevens-Johnson syndrome, in which case the hepatic injury may be overshadowed by rash and allergic symptoms.；Likelihood score: A (well established cause of clinically apparent liver injury).

The most common adverse events associated with terbinafine tend to be mild and self-limited. These include headaches, gastrointestinal symptoms, and rash. Additional uncommon but mild adverse events include visual disturbances, dysgeusia, and mild transaminitis. In rare instances, dysgeusia can be severe or permanent. However, there are reports of fulminant liver failure. Although cutaneous findings are usually non-specific, rarely Stevens-Johnson syndrome, toxic epidermal necrolysis, and cutaneous or systemic lupus erythematosus may develop.

Taste disturbances, nausea, vomiting, abdominal cramping, and headache may occur in patients taking terbinafine. Despite these untoward effects, the continuation of the medication is often dependent on the severity of symptoms and the patient's discomfort threshold. Discontinuation may be appropriate to resolve most symptoms. Although multiple symptoms may present in patients taking therapeutic or supratherapeutic doses of terbinafine, the most concerning and consistent severe adverse effects occur in the liver.；Hepatotoxicity may be asymptomatic and only detectable by lab evaluation and evidence of transaminitis. Liver enzymes over two times the normal value requires immediate discontinuation. Supportive care, including liver transplantation (in severe cases), may be necessary.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

terbinafine

Lamisil®

Antifungals

8

most-DILI-concern

◉ Summary of Use during Lactation；Limited information indicates that oral maternal doses of 500 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Monitor the infant for jaundice or other signs of liver toxicity, especially in younger, exclusively breastfed infants. Some sources recommend avoiding oral terbinafine during nursing.；Topical terbinafine has not been studied during breastfeeding. Because only about 1% is absorbed after topical application, it is considered a low risk to the nursing infant. Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only water-miscible cream, gel or liquid products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.；◉ Effects in Breastfed Infants；Relevant published information was not found as of the revision date.；◉ Effects on Lactation and Breastmilk；Relevant published information was not found as of the revision date.

Status: Active Update: 11-08-2014 https://echa.europa.eu/registration-dossier/-/registered-dossier/13147

1-Naphthalenemethanamine, N-(2E)-6,6-dimethyl-2-hepten-4-ynyl-N-methyl-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.