Clinical presentation of terbinafine-induced severe liver injury and the value of laboratory monitoring: a Critically Appraised Topic.

CONTEXT: Many physicians monitor liver function tests during terbinafine therapy.

OBJECTIVES: To evaluate the symptoms of published cases of terbinafine-associated severe drug-induced liver injury (DILI) to assess the utility of laboratory monitoring.

DATA SOURCES: We based our search on the LiverTox database of the National Institutes of Health, but we also searched both PubMed and Embase. In addition, we hand searched the references of the papers we found.

STUDY SELECTION: All reports of patients with DILI on terbinafine and with reported clinical symptoms, or absence thereof, were evaluated.

DATA EXTRACTION: Two independent reviewers (J.A. and O.N.K.) assessed articles for eligibility of inclusion, and collected and evaluated the data.

DATA SYNTHESIS: Thirty-eight papers fulfilled the inclusion criteria, with reports of 69 symptomatic patients. The mean duration of terbinafine treatment until onset of symptoms was 30·2 days (range 5-84). Symptoms in order of frequency were jaundice, flu-like symptoms, dark urine and pruritus. Patients experienced symptoms for a mean and median of 14·8 and 16 days, respectively (range 0-42) until seeking medical attention.

CONCLUSIONS: Patients who had DILI were symptomatic, usually with jaundice, abdominal pain and general malaise, but also with severe pruritus. No asymptomatic patient was identified through laboratory screening. The timeline of DILI onset varies significantly, but most cases occur between 4 and 6 weeks. There was no time point at which monitoring was meaningful, and we do not recommend monitoring of liver function tests on terbinafine; however, patients should be advised to discontinue treatment and look for medical care when symptoms of DILI occur.