Severe liver injury after treatment with the leukotriene receptor antagonist zafirlukast.
BACKGROUND
In registration trials, zafirlukast, an asthma medication, caused asymptomatic elevated aminotransferase levels in up to 5% of participants. Until now, however, no cases of severe hepatitis attributed to zafirlukast have been reported.


OBJECTIVE
To report the clinical characteristics of three patients with severe hepatitis due to zafirlukast.


METHODS
Case report.


METHODS
One community hospital and two university hospitals.


METHODS
Three middle-aged women taking zafirlukast, 20 mg twice per day.


METHODS
Discontinuation of zafirlukast therapy in three patients, steroid therapy in two patients, and orthotopic liver transplantation in one patient.


METHODS
Serum aminotransferase and bilirubin levels, standard blood tests for causes of hepatitis other than drug toxicity, and liver biopsy in two patients.


RESULTS
Patient 1 recovered spontaneously, had a severe relapse after inadvertent rechallenge with the medication, and ultimately made a complete recovery. Patient 2 developed subfulminant hepatic failure and required liver transplantation. Patient 3 developed severe hepatitis that improved after treatment with corticosteroids. Liver tissue was available from two patients and showed histologic changes commonly associated with drug reactions.


CONCLUSIONS
Patients receiving zafirlukast may develop severe liver injury and should be observed for signs and symptoms of hepatitis.
Reinus
J F
JF
Division of Gastroenterology and Hepatology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA. jreinus@montefiore.org
Persky
S
S
Burkiewicz
J S
JS
Quan
D
D
Bass
N M
NM
Davern
T J
TJ
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D018927:Anti-Asthmatic Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists; D008099:Liver / Q000201:enzymology; D017093:Liver Failure / Q000139:chemically induced / Q000601:surgery; D016031:Liver Transplantation; D008875:Middle Aged; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000009:adverse effects*
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; C062735:zafirlukast