Can cefepime cause elevated Liver Function Tests (LFTs)?

Cefepime Can Cause Elevated Liver Function Tests

Yes, cefepime can cause elevated liver function tests (LFTs), though it is a relatively uncommon adverse effect. According to the FDA drug label, increased alanine transaminase (ALT) and aspartate transaminase (AST) occur in approximately 2.8% and 2.4% of patients receiving cefepime, respectively 1.

Evidence of Cefepime-Induced Liver Injury

FDA Label Information

The FDA label for cefepime clearly documents that increased liver enzymes can occur with cefepime administration:

• ALT elevation occurs in 2.8% of patients
• AST elevation occurs in 2.4% of patients
• Increased alkaline phosphatase can also occur, though less frequently (less than 1%)
• Total bilirubin elevation has been reported (less than 1%) 1

Case Reports

Recent case reports provide stronger evidence of cefepime's potential to cause liver injury:

1. A 2023 case report documented a 99-year-old man who developed significant liver enzyme elevations (ALT 210 U/L and AST 239 U/L) after receiving cefepime for a urinary tract infection. His liver enzymes normalized after discontinuation of cefepime 2.

2. A 2019 case report described a 93-year-old man who developed cholestatic hepatitis with elevated transaminases and direct-form predominant bilirubin after cefepime administration. The patient's liver tests completely recovered after discontinuation of the drug 3.

3. A 2022 case report documented severe cholestatic drug-induced liver injury in a 27-year-old female after cefepime administration, with alkaline phosphatase peaking at 3498 IU/L and elevated AST and ALT (274 IU/L and 122 IU/L, respectively) 4.

Patterns of Liver Injury

Cefepime-induced liver injury can present in different patterns:

1. Hepatocellular pattern: Characterized primarily by elevated transaminases (ALT, AST) 2
2. Cholestatic pattern: Characterized by elevated alkaline phosphatase and bilirubin 3, 4
3. Mixed pattern: Showing features of both hepatocellular and cholestatic injury 2

Risk Factors and Monitoring

Certain patient populations may be at higher risk for cefepime-induced liver injury:

• Elderly patients
• Patients with pre-existing liver disease
• Patients with renal insufficiency (as cefepime is primarily eliminated by the kidneys) 5

Clinical Approach

When using cefepime:

1. Baseline assessment: Obtain baseline liver function tests before starting therapy, especially in high-risk patients.

2. Monitoring: Consider periodic monitoring of liver function during treatment, particularly in:

   • Patients receiving high doses (2g every 8 hours has a higher incidence of adverse effects) 1
   • Patients with pre-existing liver or kidney disease
   • Elderly patients
   • Those on prolonged therapy

3. Recognition: Be vigilant for signs of liver injury, which may include:

   • Elevated LFTs on routine blood work
   • Jaundice
   • Right upper quadrant pain
   • Nausea/vomiting
   • Fatigue

4. Management: If significant LFT elevations occur:

   • Consider discontinuation of cefepime if clinically appropriate
   • Rule out other causes of liver injury
   • Monitor LFTs until normalization
   • Consider alternative antibiotics based on culture and sensitivity results

Causality Assessment

When evaluating potential cefepime-induced liver injury, tools such as the Roussel Uclaf Causality Assessment Method (RUCAM) score or Naranjo Nomogram can help determine the likelihood of drug-induced liver injury 2, 3.

Important Considerations

• Cefepime-induced liver injury is typically reversible upon discontinuation of the drug
• The mechanism of cefepime-induced liver injury is not fully understood
• Concomitant medications with hepatotoxic potential should be evaluated when assessing causality
• Other cephalosporins have also been associated with liver injury, suggesting a possible class effect 6, 4

While cefepime-induced liver injury is uncommon, clinicians should be aware of this potential adverse effect, especially in high-risk patients, and monitor appropriately during therapy.