Correspondence

Terbinafine and Fulminant Hepatic Failure

N Engl J Med 1999; 340:1292-1293April 22, 1999

Article

To the Editor:

Terbinafine is an antifungal agent that is widely prescribed for common skin infections.1 We describe a patient who had taken terbinafine and in whom fulminant hepatic failure developed, requiring orthotopic liver transplantation.

A 48-year-old woman took 250 mg of terbinafine daily for five days for a fungal nail infection. Over the next four weeks, fulminant hepatic failure developed. The patient had been taking dothiepin (75 mg per day), which is a tricyclic antidepressant, and propranolol (40 mg twice daily) for more than 18 months. She had no risk factors for liver disease, a minimal intake of alcohol (<40 g per week), and no history of ingestion of acetaminophen or other analgesics. Serum acetaminophen levels were undetectable. Autoantibody screening and screening for serologic hepatitis A, B, and C viruses were negative; abdominal ultrasonography revealed a normal-sized liver with no evidence of splenomegaly or ascites. The patient's condition deteriorated; encephalopathy increased, requiring ventilation and intensive care. She subsequently underwent uncomplicated orthotopic liver transplantation. She remains well 18 months after transplantation.

Histologic examination of the explanted liver revealed panacinar submassive necrosis and nearly complete disappearance of hepatocytes, with no evidence of chronic liver disease. These findings are compatible with a drug-related cause of disease.

In our patient, a presumed idiosyncratic (type B) drug reaction to terbinafine may have been an important factor in the development of fulminant hepatic failure. The two other prescribed medications that she was taking have a low reported potential for hepatotoxicity, and she had been taking them for many months. Minor abnormalities in the results of liver-function tests have been reported in up to 4 percent of patients during oral treatment with terbinafine,2 with two reports of predominantly cholestatic, reversible, terbinafine-associated hepatic injury.3-5

Kosh Agarwal, M.R.C.P.
Derek M. Manas, F.C.S.(S.A.)
Mark Hudson, F.R.C.P.
Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom

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Citing Articles (10)

Citing Articles

1. 1

   Hong Liang Tey, Andy Soon Leong Tan, Yuin Chew Chan. (2011) Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. Journal of the American Academy of Dermatology 64:4, 663-670
   CrossRef

2. 2

   Zeeshan Perveze, Mark W. Johnson, Raymond A. Rubin, Marty Sellers, Carlos Zayas, Jody L. Jones, Rosemary Cross, Kimberly Thomas, Bradley Butler, Roshan Shrestha. (2007) Terbinafine-induced hepatic failure requiring liver transplantation. Liver Transplantation 13:1, 162-164
   CrossRef

3. 3

   2006. Terbinafine. , 3316-3322.
   CrossRef

4. 4

   Edith Orion, Hagit Matz, Ronni Wolf. (2005) The life-threatening complications of dermatologic therapies. Clinics in Dermatology 23:2, 182-192
   CrossRef

5. 5

   Challa Ajit, Attaya Suvannasankha, Nayere Zaeri, Santiago J. Munoz. (2003) Terbinafine-Associated Hepatotoxicity. The American Journal of the Medical Sciences 325:5, 292-295
   CrossRef

6. 6

   William M. Chambers, Andrew Millar, Stephan Jain, Andrew K. Burroughs. (2001) Terbinafine-induced hepatic dysfunction. European Journal of Gastroenterology & Hepatology 13:9, 1115-1118
   CrossRef

7. 7

   Shivakumar Chitturi, Geoffrey C. Farrell. (2000) Drug-induced liver disease. Current Treatment Options in Gastroenterology 3:6, 457-462
   CrossRef

8. 8

   James Q. Rosso. (2000) Current management of onychomycosis and dermatomycoses. Current Infectious Disease Reports 2:5, 438-445
   CrossRef

9. 9

   Boni E. Elewski. (2000) Onychomycosis. American Journal of Clinical Dermatology 1:1, 19-26
   CrossRef

10. 10

    &NA;. (1999) Terbinafine. Reactions Weekly &amp;NA;:749, 12
    CrossRef