Cefepime and Liver Toxicity
Cefepime can cause liver toxicity, but this is a rare adverse effect that is not prominently featured in major guidelines or the FDA label, with only isolated case reports documenting hepatotoxicity patterns including mixed liver injury and cholestatic hepatitis. 1, 2, 3
Evidence from FDA Labeling and Clinical Trials
The FDA-approved prescribing information for cefepime lists increased liver enzymes as adverse reactions occurring in clinical trials, specifically:
- Increased ALT (alanine transaminase) in 2.8% of patients 1
- Increased AST (aspartate transaminase) in 2.4% of patients 1
- Increased alkaline phosphatase and total bilirubin in less than 1% but greater than 0.1% of patients 1
These elevations were generally mild and detected through routine laboratory monitoring rather than clinical symptoms. 1
The cephalosporin class as a whole has been associated with hepatic dysfunction including cholestasis, though this is listed as a class effect rather than specific to cefepime. 1
Case Report Evidence of Hepatotoxicity
While rare, documented cases of cefepime-induced liver injury exist:
Mixed liver injury pattern: A 99-year-old patient developed elevated ALT (210 U/L) and AST (239 U/L) on day 4 of cefepime therapy, with enzymes returning to normal after discontinuation. 2 The Roussel Uclaf Causality Assessment Method (RUCAM) score was 7 (possible) and Naranjo score was 5 (probable). 2
Cholestatic pattern: A 93-year-old patient exhibited cholestatic hepatitis with elevated transaminases and direct bilirubin after cefepime administration, with complete recovery after drug discontinuation. 3 The RUCAM score was 7, indicating probable drug-induced liver injury. 3
Clinical Context and Risk Factors
The primary toxicity concern with cefepime is neurotoxicity, not hepatotoxicity. 4, 1, 5 Cefepime has high pro-convulsive activity and can cause encephalopathy, confusion, seizures, and nonconvulsive status epilepticus, particularly in patients with renal impairment. 4, 1, 5
Patients with both renal insufficiency and cirrhosis may be at higher risk for cefepime toxicity due to drug accumulation and increased blood-brain barrier permeability. 5
Practical Monitoring Recommendations
- Baseline liver function tests are not routinely required before initiating cefepime unless the patient has pre-existing liver disease or is receiving multiple hepatotoxic medications. 1
- If unexplained liver enzyme elevation occurs during cefepime therapy, consider cefepime as a potential cause after ruling out more common etiologies (viral hepatitis, biliary obstruction, other medications). 2, 3
- Discontinue cefepime if drug-induced liver injury is suspected, as liver enzymes typically normalize within days of discontinuation. 2, 3
- Monitor renal function closely as this is the primary risk factor for cefepime toxicity, with dose adjustment required for creatinine clearance ≤60 mL/min. 1
Important Caveats
The temporal relationship between cefepime initiation and liver enzyme elevation (typically 2-4 days) supports causality when present. 2, 3 However, cefepime-induced liver injury remains exceedingly rare compared to its neurotoxic effects, and clinicians should maintain a broader differential for hepatotoxicity in hospitalized patients receiving multiple medications. 2, 3