Liver toxicity of phenelzine?/nA man has developed hemochromatosis and a mild liver affection due t

Fråga: Liver toxicity of phenelzine?

A man has developed hemochromatosis and a mild liver affection due to thalassemia. The patient has been treated for depression with SSRI´s and tricyclic antidepressants without effect. Treatment with phenelzine (Nardil) is considered.

Sammanfattning: Hydrazine derivatives such as phenelzine may rarely cause liver toxicity, varying from a mild hepatitis to a hepatic necrosis. A suggestion for early recognition of liver toxicity, is the regular use of liver function tests, at least during the first six months of therapy. If liver toxicity develops, withdrawal of phenelzine is recommended, in order to avoid hepatic failure.

Svar: Phenelzine acts by inhibiting monoamine oxidase (MAO) A and B. The drug is extensively metabolised in the liver with less than one per cent excreted unchanged in the urine. The main pathway of metabolism is acetylation (1). The data on the hepatotoxicity of this drug are scarce (2). No cases were found in the Swedish register of adverse drug reactions.

A Medline search revealed three articles. Hydrazine derivates such as phenelzine have been described to rarely cause hepatotoxic effects such as anorexia, weakness, malaise and jaundice (3). The onset of symptoms was shown after one to six months of treatment. In patients who developed hepatic necrosis the aminotransferase levels were increased 8 to 100 times (3).

Severe acute hepatitis and portal cirrhosis verified by liver biopsy was described in a man who had taken phenelzine 45 mg daily for 70 days (4). This patient was also found to have a rapid acetylator phenotype, which according to the authors, may have predisposed to the phenelzine induced hepatitis. However, the relevance of acetylator phenotype and hepatotoxic effects has not been studied (3).

Two other cases of phenelzine exposure for four months ie 22.5 mg and 60 mg twice daily, respectively caused a fulminant hepatic failure. These cases were treated with liver transplantation (5).

The mechanism by which a hydrazine derivative such as phenelzine leads to hepatic toxicity appears to be idiosyncratic (3,5). Advanced age, simultaneous enzymatic induction by alcohol or other drugs, and coincident viral infection may play roles in the development of this clinical picture (5). 1 Dollery, Therapeutic drugs. 1991; 1: 2 Stricker BH, Drug-induced hepatic injury. 1992; 2d ed 3 Zimmerman HJ, Ishak KG: The hepatic injury of monoamine oxidase inhibitors. J Clin Psychopharmacol 1987; 7: 211-213 4 Bonkovsky HL, Blanchette PL, Schned AR: Severe liver injury due to phenelzine with unique hepatic deposition of extracellular material. Am J Med 1986; 80: 689-692 5 Gomez-Gil E, Salmeron JM, Mas A: Phenelzine induced fulminant hepatic failure. Ann Intern Med 1996; 124: 692-693