Can cefotaxime (Cefotaxime) cause liver injury?

Cefotaxime and Liver Injury

Cefotaxime can cause liver injury, though it is relatively uncommon compared to other antibiotics. The FDA drug label for cefotaxime specifically lists transient elevations in AST, ALT, serum LDH, and serum alkaline phosphatase levels as potential adverse reactions occurring in less than 1% of patients 1. More serious hepatic effects including hepatitis, jaundice, and cholestasis have been reported in post-marketing surveillance 1.

Hepatotoxicity Profile of Cefotaxime

• Transient elevations in liver enzymes (AST, ALT, LDH, alkaline phosphatase) can occur during cefotaxime treatment 1
• More serious hepatic reactions reported include hepatitis, jaundice, and cholestasis 1
• The European Association for the Study of the Liver (EASL) notes that amoxicillin/clavulanic acid is associated with a higher rate of drug-induced liver injury (DILI) compared to cefotaxime 2
• Liver chemistry monitoring should be performed when cefotaxime is used in patients with underlying liver disease 1

Risk Factors for Cefotaxime-Induced Liver Injury

• Pre-existing liver disease increases the risk of hepatotoxicity 1
• Concurrent use of other hepatotoxic medications may increase risk 3
• Patients with renal insufficiency may be at higher risk for adverse effects, including potential liver complications 1

Clinical Presentation of Cephalosporin-Induced Liver Injury

• Most cases present with asymptomatic elevations in liver enzymes 1
• When symptomatic, presentations may include jaundice, nausea, and right upper quadrant pain 4
• The pattern of liver injury with cephalosporins is typically cholestatic or mixed 4
• Onset of liver injury with cephalosporins typically occurs within 1-3 weeks after exposure 4

Comparison with Other Cephalosporins

• Cefazolin has been associated with a distinct pattern of liver injury occurring after a single dose, with a latency period of 1-3 weeks 4
• Ceftriaxone has been associated with higher rates of liver injury (19.7%) when used with other medications metabolized by the liver 3
• Ceftazidime and cefepime have been reported to cause rare cases of acute liver injury 5, 6
• Third-generation cephalosporins as a class have relatively low hepatotoxicity compared to other antibiotic classes 7

Management Recommendations

• Monitor liver function tests when using cefotaxime in patients with pre-existing liver disease 1
• If signs of liver injury develop, consider discontinuation of cefotaxime 1
• For patients with cirrhosis requiring antibiotics, cefotaxime remains a recommended first-line agent for infections such as spontaneous bacterial peritonitis, with dosing of 2g every 6-8 hours 2
• In patients with liver disease, cefotaxime has shown resolution rates of 69-98% for bacterial infections 2, 8

Alternative Antibiotics in Patients with Liver Disease

• Ceftriaxone (1g every 12-24 hours) is an effective alternative to cefotaxime with similar efficacy and safety profile 2, 8
• Amoxicillin-clavulanic acid has shown similar efficacy to cefotaxime for infections in cirrhotic patients, but carries a higher risk of drug-induced liver injury 2, 9
• Ciprofloxacin may be considered in less severe cases, but increasing resistance rates limit its utility 2, 9

In conclusion, while cefotaxime can cause liver injury, it remains a relatively safe antibiotic option even in patients with liver disease. Monitoring of liver function is recommended when using cefotaxime in patients with pre-existing hepatic impairment, and the drug should be discontinued if significant liver injury develops.