From the Guidelines
Cefepime can cause elevated liver function tests (LFTs), although the incidence is relatively low, estimated at less than 5% of patients receiving the medication. This fourth-generation cephalosporin antibiotic occasionally leads to hepatotoxicity, which manifests as increased levels of liver enzymes such as ALT, AST, alkaline phosphatase, and bilirubin 1. The elevation in LFTs typically occurs within the first few days to weeks of treatment and is usually mild and transient, resolving after discontinuation of the drug.
Mechanism and Risk Factors
The mechanism behind cefepime-induced liver injury is thought to be an idiosyncratic immune-mediated reaction rather than direct hepatotoxicity. Risk factors may include older age, pre-existing liver disease, and concomitant use of other hepatotoxic medications. If a patient on cefepime develops unexplained elevations in LFTs, particularly if accompanied by symptoms like jaundice, abdominal pain, or fatigue, healthcare providers should consider the possibility of drug-induced liver injury and evaluate whether cefepime should be discontinued or replaced with an alternative antibiotic 1.
Monitoring and Management
It is essential to monitor LFTs in patients receiving cefepime, especially those with pre-existing liver disease or risk factors for hepatotoxicity. The use of therapeutic drug monitoring (TDM) has been associated with higher clinical success and lower rate of toxicity, and is recommended mainly for drugs with a narrow ratio between efficacy and toxicity 1. In patients with severe infections, clinicians must consider the pharmacokinetic/pharmacodynamics properties of the employed antibiotics, including cefepime, to ensure optimal exposure at the infection site 1.
Key Considerations
- Cefepime-induced liver injury is relatively rare, but can occur within the first few days to weeks of treatment.
- Risk factors include older age, pre-existing liver disease, and concomitant use of other hepatotoxic medications.
- Monitoring of LFTs is essential, especially in patients with risk factors for hepatotoxicity.
- TDM may be useful in optimizing cefepime therapy and minimizing the risk of toxicity.
- If a patient on cefepime develops unexplained elevations in LFTs, healthcare providers should consider the possibility of drug-induced liver injury and evaluate whether cefepime should be discontinued or replaced with an alternative antibiotic 1.
From the FDA Drug Label
INCIDENCE EQUAL TO OR GREATER THAN 1% Positive Coombs’ test (without hemolysis) (16.2%); decreased phosphorus (2.8%); increased ALT/SGPT (2. 8%), AST/SGOT (2.4%), eosinophils (1.7%); abnormal PTT (1.6%), PT (1.4%) INCIDENCE LESS THAN 1% BUT GREATER THAN 0. 1% Increased alkaline phosphatase, BUN, calcium, creatinine, phosphorus, potassium, total bilirubin; Cephalosporin-Class Adverse Reactions ... hepatic dysfunction including cholestasis
Cefepime can cause elevated Liver Function Tests (LFT), as evidenced by increased ALT/SGPT (2.8%) and AST/SGOT (2.4%) in clinical trials. Additionally, hepatic dysfunction is listed as a potential adverse reaction for cephalosporin-class antibiotics, which includes cefepime 2.
From the Research
Cefepime and Elevated Liver Function Tests (LFTs)
- Cefepime, a fourth-generation cephalosporin, has been associated with elevated Liver Function Tests (LFTs) in several case reports 3, 4, 5.
- A case report published in the Journal of pharmacy practice described a 99-year-old male who developed severe liver injury after receiving cefepime, with alanine transferase (ALT) and aspartate transaminase (AST) levels increasing to 210 and 239 U/L, respectively 3.
- Another case report published in the Tzu chi medical journal described a 93-year-old man who developed cholestatic liver injury after receiving cefepime, with elevated blood transaminases and direct-form predominant bilirubin levels 4.
- A more recent case report published in Cureus described a 72-year-old female who developed mixed hepatocellular and cholestatic liver injury after receiving cefepime for urosepsis 5.
- These case reports suggest that cefepime can cause elevated LFTs, although the exact mechanism is not fully understood.
- It is essential to consider drug-induced liver injury (DILI) in the differential diagnosis of elevated LFTs, particularly in patients with multiple comorbidities 6, 5.
- Clinicians should be aware of the potential for cefepime-induced liver injury and monitor liver enzymes closely in patients receiving this medication 3, 4, 5.