Can ertapenem (a carbapenem antibiotic) increase Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels?

Ertapenem Can Increase AST and ALT Levels

Yes, ertapenem can cause elevations in liver enzymes including AST (aspartate aminotransferase) and ALT (alanine aminotransferase). According to the FDA drug label, drug-related laboratory adverse experiences reported in ≥2.0% of adult patients treated with ertapenem include ALT increased (6.0%) and AST increased (5.2%) 1.

Frequency and Characteristics of Liver Enzyme Elevations

• In clinical trials, ALT elevations occurred in 8.8% of adult patients receiving ertapenem compared to 7.3% in the piperacillin/tazobactam group and 8.3% compared to 6.9% in the ceftriaxone group 1, 2
• AST elevations were reported in 8.4% of patients receiving ertapenem compared to 8.3% in the piperacillin/tazobactam group and 7.1% compared to 6.5% in the ceftriaxone group 1, 2
• In pediatric patients, drug-related laboratory adverse experiences included ALT increased (2.2%) and AST increased (2.1%) 1

Mechanism and Clinical Significance

• Transaminase elevations with ertapenem are typically mild to moderate in intensity 2
• These elevations are generally transient and may not require special treatment 3
• The mechanism is likely related to direct hepatocellular effects, similar to other antibiotics that can cause drug-induced liver injury 3
• Most cases of antibiotic-induced liver enzyme elevations resolve with discontinuation of the offending agent 3

Monitoring Recommendations

• For patients receiving ertapenem, monitoring of liver function tests is recommended, particularly in those with pre-existing liver disease or risk factors for hepatotoxicity 3
• Any combination of otherwise unexplained nausea, vomiting, and abdominal pain should be evaluated with liver function tests, including ALT, AST, bilirubin, and alkaline phosphatase to assess for possible hepatotoxicity 3
• Drug-induced hepatitis should be suspected when ALT levels are ≥3 times the upper limit of normal in the presence of hepatitis symptoms, or ≥5 times the upper limit of normal in the absence of symptoms 3

Management of Elevated Liver Enzymes

• If significant elevations in liver enzymes occur (≥3 times upper limit of normal), consider temporarily withholding ertapenem and repeating blood work in 2 weeks 3
• When abnormalities return to normal, ertapenem may be restarted with close monitoring if clinically indicated 3
• Other causes of abnormal liver function tests should be excluded before diagnosing drug-induced hepatotoxicity, including viral hepatitis, biliary tract disease, alcohol use, and other hepatotoxic drugs 3

Special Populations

• No dose adjustments are required for ertapenem based on liver disease alone 4
• Dose reductions are indicated for patients with advanced renal insufficiency, which may help reduce the risk of adverse effects including liver enzyme elevations 4
• Patients with Stage 5 chronic kidney disease may be at higher risk for adverse effects from ertapenem, even with recommended dose reductions 5

Clinical Pearls

• The AST/ALT ratio can be useful in monitoring recovery from drug-induced liver injury; a ratio ≤0.4 is highly predictive of resolving transaminases 6
• Ertapenem is neither a substrate nor an inhibitor of P-glycoprotein or cytochrome P450 enzymes, so significant drug interactions affecting liver metabolism are not expected 4
• When evaluating liver enzyme elevations in patients receiving ertapenem, consider the timing of the elevation in relation to drug administration and exclude other potential causes 3