Which medication is responsible for elevated Aspartate Aminotransferase (AST) levels in a patient taking promethazine, gabapentin, hydroxyzine, levothyroxine, lorazepam, and Zofran (ondansetron)?

Ondansetron is Most Likely Responsible for Elevated AST Levels

Based on the FDA drug label and available evidence, ondansetron (Zofran) is the medication most likely responsible for the elevated AST levels in this patient's medication regimen.

Medication Review and Hepatotoxicity Potential

• Ondansetron (Zofran): The FDA drug label specifically lists elevated liver enzymes as a known adverse effect, stating "Aspartate transaminase (AST) and/or alanine transaminase (ALT) values exceeded twice the upper limit of normal in approximately 1% to 2% of patients receiving ondansetron tablets" 1. A case report confirms ondansetron can cause aminotransferase elevations even in patients without cancer or chemotherapy treatment 2.

• Hydroxyzine: Not typically associated with significant liver enzyme elevations in available guidelines.

• Gabapentin: Generally not associated with significant hepatotoxicity in the reviewed evidence.

• Levothyroxine: Not commonly associated with significant liver enzyme elevations in the reviewed literature.

• Lorazepam: Not typically associated with significant liver enzyme elevations in the reviewed guidelines.

• Promethazine: Not specifically identified as causing significant AST elevations in the reviewed evidence.

Clinical Considerations for Ondansetron-Induced Liver Enzyme Elevation

• Ondansetron-induced AST/ALT elevations are typically transient and not dose-related 1, 2.

• These elevations usually do not progress to symptomatic liver disease or permanent liver damage 1.

• The elevations typically resolve upon discontinuation of the medication 2.

• In a case report, a patient with no oncologic history experienced AST elevations several times the upper limit of normal within one day of receiving intravenous ondansetron on three separate occasions 2.

Diagnostic Approach

• When evaluating elevated AST in a patient on multiple medications, consider the AST/ALT ratio, which can help differentiate between various causes of liver injury 3, 4.

• Rule out other common causes of elevated liver enzymes including:

  • Viral hepatitis (hepatitis A, B, C) 5
  • Alcohol consumption 5
  • Non-alcoholic steatohepatitis (NASH) 5
  • Muscle injury (which can elevate AST more than ALT) 6

• If AST elevation persists after discontinuation of ondansetron, consider further evaluation for other causes 5.

Management Recommendations

• Consider discontinuation of ondansetron if clinically appropriate 2.

• Monitor liver enzymes after discontinuation to confirm resolution 1.

• If antiemetic therapy is still needed, consider switching to an alternative antiemetic with less potential for hepatotoxicity 1.

• If AST elevation does not resolve after discontinuation, further diagnostic evaluation is warranted to rule out other causes 5.

Important Caveats

• Patients with pre-existing liver disease may be at higher risk for medication-induced liver enzyme elevations 6.

• Concomitant use of multiple potentially hepatotoxic medications can increase the risk of liver enzyme elevations 6.

• Non-hepatic causes of AST elevation (such as muscle injury) should be considered in the differential diagnosis 5.