Can Rocephin (Ceftriaxone) cause elevated Liver Function Tests (LFTs)?

Can Rocephin (Ceftriaxone) Cause Elevated Liver Function Tests?

Yes, Rocephin (ceftriaxone) can cause elevated liver function tests (LFTs), with the FDA drug label specifically listing hepatic dysfunction and elevated LFTs as known adverse effects of the medication. 1, 2

Evidence for Ceftriaxone-Induced LFT Elevations

FDA Drug Label Information

The FDA-approved drug label for ceftriaxone clearly documents that:

• Elevated liver function tests are listed as a known adverse reaction
• Specifically, elevations of alkaline phosphatase and bilirubin are reported in approximately 1% of patients 1
• "Hepatic dysfunction including cholestasis" is listed among the cephalosporin class adverse reactions 2

Recent Research Evidence

A 2022 retrospective study found a significantly higher incidence of liver injury than previously reported:

• 19.7% of patients treated with ceftriaxone experienced liver injury
• This risk increased when ceftriaxone was combined with other medications metabolized by the liver 3
• The incidence was "too high to be ignored in clinical practice" according to the researchers 3

Another 2022 case report described acute non-cholestatic liver injury occurring within 48 hours of ceftriaxone administration, with progressive clinical improvement after discontinuation of the drug 4.

Mechanism and Clinical Presentation

Ceftriaxone-induced liver injury typically presents as:

• Elevated serum levels of liver enzymes (AST, ALT)
• Possible elevations in gamma-glutamyl transferase and bilirubin
• Rarely, cases of acute liver damage have been reported 5

The mechanism appears to involve:

• Possible immune-cytopathic damage
• Direct cytotoxicity
• Inflammatory response 5

Clinical Considerations

Monitoring Recommendations

• Baseline LFTs should be obtained before initiating therapy
• Regular monitoring of liver function is necessary, especially when using ceftriaxone with other potentially hepatotoxic drugs 5
• If a patient on ceftriaxone develops abnormal liver function, appropriate serological tests should be performed to rule out other causes 5

Management of LFT Abnormalities

If LFT elevations occur during ceftriaxone therapy:

1. Assess the severity of elevation
2. Consider discontinuation if clinically significant elevations occur
3. Evaluate for other potential causes of liver dysfunction
4. In most cases, hepatic dysfunction is transient and does not require special treatment beyond drug discontinuation 5

Important Caveats

• The risk of significant hepatotoxicity appears to be relatively low compared to other adverse effects
• Most LFT elevations are mild and transient
• Severe hepatotoxicity is rare but can occur
• It may be difficult to distinguish whether liver dysfunction is due to ceftriaxone itself, disease complications, or effects of other medications 5

When evaluating abnormal LFTs in a patient on ceftriaxone, consider other common causes such as viral hepatitis, pre-existing liver disease, or concomitant hepatotoxic medications before attributing the abnormality solely to ceftriaxone.