Terbinafine-induced hepatic failure requiring liver transplantation

Abstract

Drug-induced liver disease accounts for about 50% of acute or subacute liver failure in the United States. United Network of Organ Sharing (UNOS) data suggest 8%-20% of liver transplantation in this country per year is for fulminant liver failure due to drugs. Even though the most common medication implicated in acute liver injury is acetaminophen (75%), there are numerous other drugs that are responsible for acute and chronic liver injury. A variety of antifungal medications are known to cause a wide range of liver injury from a mild hepatocellular-cholestatic injury pattern to acute/subacute liver failure. Terbinafine is one of the antifungals that have been associated with such liver injuries. We report a case of terbinafine-induced severe liver failure requiring liver transplantation. Liver Transpl 13: 162-164, 2007.

Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis

“…13 Inducers of the cytochrome P450 system, such as rifampin, may increase the metabolism of terbinafine and the converse may occur with inhibitors of the cytochrome P450 system, such as cimetidine. 12,13 Rare cases of liver failure have occurred with the use of terbinafine 14,15 and a metabolic idiosyncratic reaction has been proposed to be the underlying mechanism. 15 As a result, the manufacturer has recommended obtaining serum transaminase levels before treatment for all patients, especially those with pre-existing hepatic impairment, those on concurrent hepatotoxic medications, and alcoholics.…”

“…12,13 Rare cases of liver failure have occurred with the use of terbinafine 14,15 and a metabolic idiosyncratic reaction has been proposed to be the underlying mechanism. 15 As a result, the manufacturer has recommended obtaining serum transaminase levels before treatment for all patients, especially those with pre-existing hepatic impairment, those on concurrent hepatotoxic medications, and alcoholics. 16 In patients with renal impairment (ie, creatinine clearance of # 50 mL/min), the use of terbinafine is not recommended 16 as clearance of the drug may be decreased substantially.…”

Evaluation of the Morphological Effects of TDT 067 (Terbinafine in Transfersome) and Conventional Terbinafine on Dermatophyte Hyphae In Vitro and In Vivo

“…The treatment of onychomycosis has improved considerably following the introduction of the oral antifungals terbinafine and itraconazole (21). However, drug-drug interactions and hepatotoxicity have been associated with these oral antifungals (1,15,20), and there are still a proportion of patients who do not achieve efficacy (25). Elderly patients are at increased risk of onychomycosis (26).…”

Terbinafine Induced Liver Injury: A Case Report

“…6,7 Most of the cases recover after discontinuation of the drug, however, rarely Terbinafine may cause acute or subacute liver failure requiring liver transplantation. 8 Possible mechanisms of Terbinafine related liver injury include reaction to allylic aldehyde metabolite that may bind to hepatobiliary proteins to cause direct toxicity or by causing immune-mediated reaction to canalicular proteins leading to cholestasis. 9 The histopathologic examination of liver biopsies generally show a mixed picture of hepatitis and cholestasis.…”