Fungal nail infection medication

[Guest guest]

About 15 years ago I had oral medication for 3-6 months, to get rid of

a fungal nail infection. I now heard that this type of medication

(e.g. terbinafine) may cause liver damage. Does anyone know if there

is any association with psc (or psc-like symptoms)?

Happy holidays,

Gerard

[Guest guest]

Hi Gerard;

The liver damage caused by terbinafine does seem to be PSC-like (i.e.

cholestasis), but it usually resolves after discontinuation of the

drug. Here are 4 abstracts from the PubMed database describing the

liver toxicity associated with terbinafine.

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1: Ann Hepatol. 2003 Jan-Mar;2(1):47-51.

Terbinafine hepatotoxicity. A case report and review of literature.

Zapata Garrido AJ, Romo AC, Padilla FB.

Hospital Christus Muguerza, Monterrey, Nuevo León, Mexico.

We report a 53-year old Mexican female who developed liver dysfunction

following a seven-day course of treatment with terbinafine for

onychomycosis. She presented with jaundice and abdominal pain. Her

serum bilirubin levels showed a peak value of 23.2 mg/dL seven weeks

after discontinuing the medication. Infectious causes (hepatitis

viruses A, B and C) were excluded. Imaging studies of the abdomen did

not reveal any abnormalities. Serum iron and ceruloplasmin levels were

normal. Autoantibodies were negative. A liver biopsy revealed necrosis

and mononuclear infiltration of the parenchyma, mainly along the

sinusoids and surrounding the portal spaces and biliary ducts.

Eosinophil infiltration of the portal spaces was also noted. Treatment

with ursodeoxycholic acid and ademethionine was started. Her liver

tests normalized in the sixth months after stopping terbinafine.

PMID: 15094707

________________

2: Am J Med Sci. 2003 May;325(5):292-5.

Terbinafine-associated hepatotoxicity.

Ajit C, Suvannasankha A, Zaeri N, Munoz SJ.

Department of Internal Medicine, Lankenau Hospital, Wynnewood,

Pennsylvania, USA.

Terbinafine, an orally and topically active agent licensed for

treatment of dermatophytic infection, has gained rapid worldwide

acceptance in medical practice. Despite its fairly benign profile of

adverse reactions, liver toxicity has occasionally been linked to

terbinafine. This report describes a patient with severe cholestatic

hepatitis associated with use of terbinafine. The patient was treated

successfully with corticosteroids after partial response to

ursodeoxycholic acid and cholestyramine. We attempt to identify risk

factors for terbinafine-induced hepatotoxicity by an analytical review

of all relevant literature. The mechanism underlying terbinafine

hepatotoxicity could be more than just an idiosyncratic reaction. 7,7-

dimethylhept-2-ene-4-ynal (TBF-A), the allylic aldehyde metabolite of

terbinafine, may play a role in the pathogenesis of its hepatotoxicity.

Our analysis supports monitoring patients clinically and measuring

liver biochemistry through periodic blood tests, after confirming

normal liver function at the onset of therapy with terbinafine. Early

detection of abnormal hepatic function should prompt immediate

discontinuation of this drug along with further evaluation. PMID:

12792250

________________

3: Chem Res Toxicol. 2001 Feb;14(2):175-81.

Identification of a reactive metabolite of terbinafine: insights into

terbinafine-induced hepatotoxicity.

Iverson SL, Uetrecht JP.

Faculties of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

Oral terbinafine treatment for superficial fungal infections of toe and

fingernails is associated with a low incidence (1:45000) of

hepatobiliary dysfunction. Due to the rare and unpredictable nature of

this adverse drug reaction, the mechanism of toxicity has been

hypothesized to be either an uncommon immunological or metabolically

mediated effect. However, there is little evidence to support either

mechanism, and toxic metabolites of terbinafine have not been

identified. We incubated terbinafine with both rat and human liver

microsomal protein in the presence of GSH and were able to trap an

allylic aldehyde, 7,7-dimethylhept-2-ene-4-ynal (TBF-A), which

corresponds to the N-dealkylation product of terbinafine. TBF-A was

also prepared synthetically and reacted with excess GSH to yield

conjugates with HPLC retention times and mass spectra identical to

those generated in the microsomal incubations. The major GSH conjugate,

characterized by (1)H NMR, corresponds to addition of GSH in a 1,6-

fashion. There remains a second electrophilic site on this

metabolite, which can bind either to a second molecule of GSH or to

cellular proteins via a 1,4- addition mechanism. Moreover, we

demonstrated that the formation of the GSH conjugates was reversible.

We speculate that this allylic aldehyde metabolite, formed by liver

enzymes and conjugated with GSH, would be transported across the

canalicular membrane of hepatocytes and concentrated in the bile. The

mono-GSH conjugate, which is still reactive, could bind to

hepatobiliary proteins and lead to direct toxicity. Alternatively, it

could modify canalicular proteins and lead to an immune-mediated

reaction causing cholestatic dysfunction. PMID: 11258966.

________________

4: Am J Gastroenterol. 1998 Mar;93(3):459-60.

Terbinafine hepatotoxicity: case report and review of the literature.

Fernandes NF, Geller SA, Fong TL.

Center for Liver Diseases and Transplantation and Department of

Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los

Angeles, California 90048, USA.

We report a patient who developed significant liver dysfunction

following therapy with terbinafine. At the end of a 3 1/2-wk course of

terbinafine, he developed progressive jaundice and pruritus. His serum

bilirubin peaked at 30.9 mg/dl 3 wk after discontinuing terbinafine. A

liver biopsy revealed mild to moderate mixed cellular infiltrate in the

portal tracts, and hepatocellular and canicular cholestasis. His liver

PMID: 9517658.

________________

Best regards,

Dave R.

>

> About 15 years ago I had oral medication for 3-6 months, to get rid

of

> a fungal nail infection. I now heard that this type of medication

> (e.g. terbinafine) may cause liver damage. Does anyone know if there

> is any association with psc (or psc-like symptoms)?

>

> Happy holidays,

>

> Gerard

>