Letters to the Editor
Effect of Olanzapine on the Liver Transaminases
Dear Editor:
The effect of olanzapine on liver transaminases is among the less frequently encountered side effects of this novel atypical antipsychotic drug. Initial clinical trials observed a transient, asymptomatic, non–dose-dependent elevation in the liver transaminases in 9.4% of olanzapine-treated patients (1).
Although this suggests an increased risk for hepatitis, it has been argued that there has been no evidence of hepatitis in the patients (2). Some reports suggest that an even smaller percentage—1.9% in more than 2000 patients receiving olanzapine—had elevated enzyme levels, which gradually declined with continued treatment (3).
The Canadian Adverse Drug Reaction Monitoring Program (CADRMP), however, has received 9 reports of olanzapine causing mainly mild increases in alanine aminotransferase (ALT).
We report 2 cases wherein olanzapine caused significant elevation of liver transaminases, up to 5 times the normal reference range.
The first case is a woman, age 37 years, who presented with auditory hallucinations and religious delusions. This was her first psychotic episode postpartum. On admission, her liver transaminases were minimally elevated (ALT = 95 U/L > asparate aminotransferase [AST] 50 U/L). The normal range is ALT = 7 U/L to 40 U/L and AST = 7 U/L to 40 U/L. She had been taking 5 mg daily of olanzapine prior to admission, and the enzyme levels prior to initiation of olanzapine were not known. The dosage was increased to 10 mg daily, and liver transaminases were closely monitored. The enzymes continued to increase rapidly to about 4 to 5 times the normal reference range (ALT 237 U/L max) over the next 10 days. The drug was discontinued, and the enzyme levels gradually normalized after 4 days.
In the second case, a woman aged 62 years, with a long history of schizophrenia, did not respond to risperidone and was switched to olanzapine. She had been on 5 mg daily of olanzapine, which her primary psychiatrist in the clinic gradually increased to 15 mg daily. After she had been on olanzapine for a month, we incidentally found a significant increase in her liver transaminases (ALT = 179 U/L and AST = 115 U/L), following her hospitalization for delirium secondary to pneumonia. Olanzapine was then discontinued. For the next 4 days, her ALT fluctuated between 137 U/L and 180 U/L before it normalized.
Both these patients did not have any clinical evidence of liver dysfunction. The remainder of the liver panel was normal, except for a decrease in albumin in the second case, which normalized after stopping olanzapine. All other causes of elevation of liver transaminases were ruled out.
The relevance of elevated transaminases remains controversial. Mild elevations have been reported with the use of olanzapine. However, relevance of marked increase in liver enzymes (> 3 to 4 times the normal reference range) remains to be elucidated.
It is unclear whether these patients can be rechallenged with this drug. Thus, further research is warranted to address the relevance of elevated enzymes.
References
1. Beasley CM. Safety of olanzapine. Monograph 15. J Clin Psychiatry 1997;15(2):19–21.
2. Shulman RW. Drug review “surprises” reader. Can Fam Physician 2000;46:2381–3.
3. Zyprexa Product Monograph. Compendium of pharmaceuticals and specialties. 35th ed. Ottawa (ON): Canadian Pharmacists Association; 2000.
Manasi Kolpe, MD;
Sajid Ravasia, MD
Fargo, North Dakota
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