Can Ceftriaxone Cause Transaminitis?
Yes, ceftriaxone can cause transaminitis (elevated liver enzymes), though it is generally uncommon and typically reversible upon discontinuation. 1
Incidence and Clinical Significance
The FDA drug label reports that elevations of AST occur in 3.1% of patients and ALT elevations in 3.3% of patients treated with ceftriaxone. 1 Less frequently (<1%), elevations of alkaline phosphatase and bilirubin also occur. 1
However, real-world data suggests the incidence may be higher in certain populations:
- A 2022 retrospective study from Qatar found a 19.7% incidence of liver injury in hospitalized patients receiving ceftriaxone, particularly when combined with other hepatically-metabolized medications. 2
- The risk appears substantially elevated compared to historical estimates of 2.9-13.9% when ceftriaxone is used alongside other drugs utilizing hepatic metabolism. 2
Mechanism and Patterns of Liver Injury
Ceftriaxone-induced hepatotoxicity can manifest as cholestasis, transaminitis, or mixed patterns, often associated with biliary "sludging" of the drug in the gallbladder. 3 The precipitation of ceftriaxone-calcium complexes in bile can lead to:
- Gallbladder sludge and biliary pseudolithiasis 1, 4
- Symptomatic precipitation causing cholestasis 1
- Marked direct hyperbilirubinemia, particularly in patients with underlying liver abnormalities 5
High-Risk Populations
Certain patient groups warrant closer monitoring:
- Patients with sickle cell disease: A case report documented marked direct hyperbilirubinemia (total bilirubin rising from 3.3 to 17 mg/dL) in a sickle cell patient with chronic baseline liver abnormalities. 5
- Patients on polypharmacy: Multivariate analysis shows ceftriaxone is independently associated with liver injury, especially when combined with other hepatically-metabolized agents. 2
- High-dose therapy (4g/day): While a 2022 study found comparable liver enzyme elevations between 2g and 4g daily dosing (10.6% vs 5.1%), absolute development of hepatic dyscrasias remains appreciable at both doses. 6
Monitoring Recommendations
For patients receiving prolonged ceftriaxone therapy (≥7 days), monitor liver function tests and full blood count regardless of dosing regimen. 6 This is particularly important because:
- Median time to development of liver abnormalities varies but can occur within the first week of therapy 6
- The injury pattern is typically reversible with drug discontinuation 5
- Rare cases can progress to complete liver failure if not recognized 2
Clinical Management
When elevated transaminases or bilirubin develop during ceftriaxone therapy with no other identifiable cause, discontinue the drug promptly. 5 Clinical and biochemical improvement typically occurs within 72 hours to several days after cessation. 5, 7
Important Caveats
Despite the hepatotoxicity risk, ceftriaxone remains a first-line antibiotic for serious infections in patients with liver disease, including:
- Spontaneous bacterial peritonitis in cirrhosis (cefotaxime or ceftriaxone are preferred) 8, 9
- Gastrointestinal bleeding prophylaxis in advanced cirrhosis 8, 9
- Community-acquired pneumonia in decompensated cirrhosis 9
Third-generation cephalosporins like ceftriaxone generally do not require dosage adjustment in hepatic dysfunction and are considered among the safest antibiotics for patients with significant liver disease. 9 The benefits typically outweigh risks in these clinical scenarios, though monitoring remains essential.