Is Transaminitis Common with Ceftriaxone or Azithromycin?
Transaminitis is not a common side effect of either ceftriaxone or azithromycin, though both can cause mild, reversible liver enzyme elevations in a small percentage of patients.
Ceftriaxone and Liver Effects
Ceftriaxone can cause hepatobiliary complications, but true transaminitis is uncommon:
Liver function abnormalities can occur with ceftriaxone use, often associated with biliary "sludging" of the drug in the gallbladder rather than direct hepatotoxicity 1
Marked direct hyperbilirubinemia with mild transaminitis has been documented in case reports, particularly in patients with underlying conditions like sickle cell disease who have baseline liver chemistry abnormalities 2
In the sickle cell case report, total bilirubin rose from 3.3 mg/dL to 17 mg/dL with only mild transaminase elevation; symptoms resolved after switching to levofloxacin 2
The mechanism appears related to ceftriaxone precipitation in bile causing cholestasis and reversible biliary sludge, rather than direct hepatocellular injury 2
Azithromycin and Liver Effects
Azithromycin is generally well-tolerated with minimal hepatic effects:
Common side effects include gastrointestinal complaints (abdominal discomfort, diarrhea, nausea, vomiting) rather than liver enzyme abnormalities 3
In clinical trials, gastrointestinal side effects occurred in 35.3% of patients receiving azithromycin 2g for gonorrhea, but hepatotoxicity was not reported as a significant adverse effect 4
Dose-related gastrointestinal complaints are more common than hepatic effects, with incident nausea or vomiting rates of approximately 3% in non-gastrointestinal infections 1
Clinical Context and Monitoring
When these antibiotics are used together (a common combination for community-acquired pneumonia):
The combination of azithromycin and ceftriaxone does not appear to increase adverse events beyond what would be expected from either agent alone 5, 6
In a Brazilian study of 86 inpatients treated with IV azithromycin plus ceftriaxone followed by oral azithromycin, the regimen proved efficacious and well-tolerated without significant hepatotoxicity reported 7
Key Clinical Pitfalls
In patients developing hyperbilirubinemia on ceftriaxone, particularly those with chronic liver chemistry abnormalities, consider ceftriaxone-induced cholestasis and discontinue the drug 2
Expect rapid improvement (within 72 hours) after discontinuing ceftriaxone if it is the causative agent 8
Do not confuse biliary sludging/cholestasis (elevated bilirubin with mild transaminase elevation) with true hepatocellular injury (marked transaminase elevation) 2
Baseline liver abnormalities may predispose patients to more pronounced ceftriaxone-related biliary effects 2