Do you discontinue Zyprexa (olanzapine) if liver enzymes are elevated?

Management of Elevated Liver Enzymes During Olanzapine (Zyprexa) Treatment

Yes, olanzapine (Zyprexa) should be discontinued if liver enzymes are significantly elevated, particularly if ALT/AST is greater than 3 times the upper limit of normal (ULN) and continues to rise despite dose reduction. 1

Liver Enzyme Monitoring and Thresholds for Discontinuation

• According to the FDA drug label for olanzapine, clinically significant ALT elevations (≥3 times ULN) were observed in 5% of adult patients and 12% of adolescent patients treated with olanzapine, compared to 1% and 2% in placebo groups, respectively 1
• For adults with baseline ALT ≤90 IU/L, the incidence of ALT elevations to >200 IU/L was 2% during olanzapine treatment 1
• ALT elevations ≥5 times ULN were observed in 2% of adult patients and 4% of adolescent patients on olanzapine 1

Decision Algorithm for Managing Elevated Liver Enzymes with Olanzapine

When to Discontinue Olanzapine

• Immediately discontinue if:
  • ALT/AST >3 times ULN with symptoms (fatigue, nausea, right upper quadrant pain, jaundice) 2
  • ALT/AST >3 times ULN with total bilirubin >2 times ULN or INR >1.5 2
  • ALT/AST >8 times ULN in patients with normal baseline liver enzymes 2
  • ALT/AST continues to rise despite dose reduction 3

When to Consider Dose Reduction

• Consider dose reduction if:
  • ALT/AST is 2-3 times ULN without symptoms 3
  • Patient has risk factors for hepatotoxicity (geriatric age, pediatric age, obesity, concomitant hepatotoxic medications) 3

Monitoring Recommendations

• Baseline liver function tests before starting olanzapine 4
• Regular monitoring during the first 6 months of treatment, with more frequent monitoring (every 2-5 days) if enzymes begin to rise 2
• After 6 months, periodic monitoring should continue, especially in high-risk patients 4

Clinical Course of Liver Enzyme Elevations

• Most liver enzyme elevations with olanzapine are asymptomatic and transient 1
• ALT values typically return to normal or decrease while continuing olanzapine treatment or after discontinuation 1
• In a chart review study, 27.2% of patients showed asymptomatic increases in liver enzymes in the first month of atypical antipsychotic treatment, decreasing to 22.7% after 6 months 4
• Only 1.8% of patients required treatment discontinuation due to significant elevations (>3-4 times ULN) 4

Comparison with Other Antipsychotics

• Liver enzyme elevations appear to be more common with olanzapine than with risperidone 5
• In comparative studies, frequencies of ALT elevations were higher in olanzapine-treated groups than risperidone-treated groups, with longer recovery and latency times 5
• The incidence of enzyme elevations is slightly more frequent with clozapine and olanzapine compared to risperidone, perazine, and haloperidol 3

Important Considerations and Pitfalls

• Do not ignore even modest enzyme elevations if accompanied by symptoms of liver injury 2
• Avoid premature discontinuation for mild, asymptomatic elevations as these may be transient 2
• Consider all potential causes of liver enzyme elevations, including concomitant medications, alcohol use, and underlying liver disease 2
• Be particularly vigilant in high-risk populations: geriatric patients, adolescents, and those with obesity or taking other hepatotoxic medications 3

Resumption of Treatment

• Olanzapine may be cautiously restarted at a lower dose after liver enzymes normalize if no other cause for the elevation is identified 6
• Do not restart if the patient experienced clinical symptoms of hepatitis or if ALT/AST was >3 times ULN without another explanation 2
• Consider alternative antipsychotics with potentially lower hepatotoxicity risk if appropriate for the patient's condition 5