How does cefepime affect Liver Function Tests (LFTs)?

Cefepime's Effects on Liver Function Tests

Cefepime rarely causes liver function test abnormalities, but monitoring is recommended as it can occasionally cause drug-induced liver injury with elevations in transaminases (ALT/AST) in a hepatocellular pattern. 1

Pharmacokinetics and Hepatic Metabolism

Cefepime is primarily eliminated through renal excretion, with approximately 85% of the drug excreted unchanged in urine. According to the FDA label, cefepime pharmacokinetics are unaltered in patients with hepatic impairment who received a single 1g dose 2. This is a key distinction from many other antibiotics that require hepatic metabolism.

Key points about cefepime and the liver:

• Cefepime does not require dose adjustment in hepatic impairment 2
• The drug undergoes minimal hepatic metabolism (less than 1% is metabolized to N-methylpyrrolidine)
• Liver dysfunction does not significantly affect cefepime clearance

Potential for Liver Injury

While rare, cefepime can cause drug-induced liver injury. A recent case report from 2023 documented a 99-year-old patient who developed elevated liver enzymes after starting cefepime therapy:

• ALT increased from 22 to 210 U/L
• AST increased from 44 to 239 U/L
• Enzyme levels peaked on day 4 of treatment
• Liver enzymes returned to normal after cefepime discontinuation 1

This pattern suggests a hepatocellular type of liver injury rather than cholestatic injury.

Monitoring Recommendations

Although cefepime-induced liver injury is uncommon, monitoring of liver function tests is prudent in certain situations:

1. Baseline LFTs: Consider obtaining baseline liver function tests before initiating therapy
2. Periodic monitoring: Monitor LFTs during prolonged therapy (>7 days)
3. High-risk patients: More frequent monitoring in patients with:
   • Pre-existing liver disease
   • Concomitant hepatotoxic medications
   • Advanced age
   • Renal insufficiency (as this can lead to cefepime accumulation) 3

Risk Factors for Cefepime-Related Hepatotoxicity

Patients with the following characteristics may be at higher risk for cefepime-induced liver injury:

• Renal insufficiency (leading to drug accumulation)
• Cirrhosis (which may increase blood-brain barrier permeability and alter drug distribution) 3
• Advanced age
• Concomitant use of other hepatotoxic medications

Clinical Presentation of Cefepime-Induced Liver Injury

When cefepime causes liver injury, it typically presents as:

• Asymptomatic elevation in transaminases
• Hepatocellular pattern of injury (predominant elevation in ALT/AST)
• Temporal relationship to drug initiation (usually within 2-7 days)
• Resolution upon drug discontinuation

Management of Suspected Cefepime-Induced Liver Injury

If liver enzyme elevations are detected during cefepime therapy:

1. Evaluate for other causes of liver injury
2. Consider discontinuation of cefepime if:
   • ALT/AST >3 times upper limit of normal
   • No other identifiable cause
   • Pattern and timing are consistent with drug-induced liver injury
3. Monitor liver enzymes after discontinuation to confirm improvement

Comparison with Other Cephalosporins

Cephalosporins as a class can cause hepatic adverse effects, including:

• Transient elevation of liver enzymes
• Cholestatic hepatitis
• Hepatic dysfunction including cholestasis 2

However, cefepime appears to have a lower incidence of hepatotoxicity compared to some other cephalosporins. For example, ceftazidime has also been reported to cause drug-induced liver injury in a hepatocellular pattern 4.

Conclusion

While cefepime primarily undergoes renal elimination and does not require dose adjustment in hepatic impairment, it can rarely cause drug-induced liver injury. Monitoring of liver function tests is advisable, particularly in high-risk patients or those on prolonged therapy. If significant elevations in liver enzymes occur during treatment, consider cefepime as a potential cause and evaluate for discontinuation if appropriate.