Which Drug Causes Transaminitis?
All four medications can cause transaminitis (elevated liver enzymes), but linezolid and ceftriaxone are the most clinically significant offenders, with NSAIDs (not listed but mentioned in guidelines) being well-documented hepatotoxic agents.
Ceftriaxone and Hepatotoxicity
Ceftriaxone can cause transaminitis and cholestatic liver injury, though this is generally uncommon. 1, 2
- Liver function abnormalities occur with ceftriaxone use and are sometimes associated with "sludging" of drug in the gallbladder 3
- In a retrospective study of outpatients, elevated liver enzymes occurred in 10.6% of patients receiving standard dose (2g/day) and 5.1% receiving high dose (4g/day) ceftriaxone 2
- Ceftriaxone has been associated with marked direct hyperbilirubinemia and mild transaminitis, particularly in patients with underlying liver abnormalities such as sickle cell disease 1
- The hepatotoxicity is typically reversible upon discontinuation of the drug 1
Linezolid and Hepatotoxicity
Linezolid causes elevated liver enzymes as a recognized adverse effect, occurring in approximately 2-3% of treated patients. 4
- In a pediatric study, elevated liver enzymes were detected in 4 out of 179 patients (2.2%) receiving linezolid 4
- Adverse effects from linezolid, including transaminitis, can occur within the first 10 days of therapy—72.2% of adverse effects were detected within this timeframe 4
- Monitoring of liver enzyme levels is specifically recommended during linezolid therapy 4
Acyclovir and Hepatotoxicity
Acyclovir can cause transaminitis, though this is less commonly emphasized in clinical practice compared to its renal toxicity. 5
- The COVID-19 treatment guidelines note that various antiviral medications can cause elevated transaminases, though specific data on acyclovir hepatotoxicity was not detailed in the provided evidence 5
Heparin and Hepatotoxicity
Heparin can cause transaminitis, typically presenting as asymptomatic transaminase elevations that are usually transient and clinically insignificant.
- While not extensively detailed in the provided evidence, heparin-induced transaminitis is a recognized phenomenon in clinical practice, though it is generally mild and self-limited
Clinical Context from NSAIDs (Reference Point)
The guidelines provide useful context by noting that NSAIDs can cause hepatic complications including transaminitis, with certain agents like sulindac and diclofenac having more hepatotoxic potential 5. Primary hepatic complications from NSAIDs are rare and usually reversible 5.
Practical Monitoring Recommendations
- For linezolid: Monitor liver enzymes and platelet counts, especially during the first 10 days of therapy 4
- For ceftriaxone: Consider monitoring liver function in patients with pre-existing liver disease or those receiving prolonged therapy (>7 days) 2
- For all agents: Discontinue the offending medication if significant transaminitis develops and investigate alternative causes 1