The Australian Therapeutic Goods Administration (TGA), the Australian equivalent to the Saudi Food and Drug Authority (SFDA), has recently published the February 2008 issue of the Australian Adverse Drug Reactions Bulletin which included a topic titled  “Hepatic reactions with Terbenafine”.

Oral Terbenafine, marketed as (Lamisil) or (Lamifen) was approved in Saudi Arabia in 2002 as a treatment of fungal infections of the nails and skin (ringworm) that are not responsive to topical therapy.

The TGA’s Adverse drug reactions advisory committee (ADRAC) is concerned that in some cases the oral form of Terbenafine may be selected without any trial of topical therapy, thereby putting the patient at risk of rare but serious and life-threatening toxicities such as agranulocytosis and other blood dyscrasias, Stevens-Johnson syndrome, and liver failure.

ADRAC has previously drawn attention to serious adverse reactions associated with orally administered Terbenafine. Recently, the Committee reviewed a report describing an 81 year old female with previously normal liver function who developed cholestatic hepatitis some 3 weeks after commencing oral Terbenafine treatment 250 mg daily for a fungal infection of the big toe. The patient subsequently died in hepatorenal failure.

Of the total 722 adverse event reports received up to January 2008 in connection with Terbenafine (all dose forms), 70 describe hepatic reactions and most (61) implicated oral Terbenafine as the sole suspected drug. Onychomycosis was the most commonly cited reason for use of Terbenafine; patient age ranged from 20 to 85 (median 58) years, and men and women were affected equally.

Half of the reports documented onset of hepatic reaction within the first month and 80% within 7 weeks. Most of the reports document minor abnormalities of liver function but 3 describe fatal liver failure, 10 describe hepatitis, and 12 describe jaundice. Full recovery was noted in 27 reports but 34 cases had not recovered and the outcome remained unknown in 9.

Actions That Healthcare Professionals Should Follow:

• Prescribers are reminded that oral Terbenafine can be associated with rare but serious and life threatening toxicities.
• Physicians prescribing oral Terbenafine should be confident there is a clear indication for its use.
• Oral Terbenafine should be prescribed only after topical therapy has failed and for the shortest time possible, in accordance with the current Product Information.

Report Adverse Drug Reactions to The Saudi FDA:
The public and health professionals are encouraged to report adverse drug reactions the National Pharmacovigilance Center on the Internet at: