Drugs Causing Transaminitis

Antituberculosis Medications

Isoniazid causes hepatotoxicity in approximately 1% of patients overall, with age-related risk escalating from essentially 0% in patients under 20 years to 2.3% in those over 50 years 1
Daily alcohol consumption increases the risk of isoniazid hepatitis fourfold 1
The rifampin/pyrazinamide combination shows similar hepatotoxicity rates to isoniazid in clinical trials 1
Rifampin was the most commonly implicated drug causing adverse reactions in 12% of HIV-positive TB patients in one retrospective study 2
HIV-infected patients with concurrent hepatitis C virus infection have a 14-fold increased relative risk of drug-induced hepatotoxicity compared to those without these infections 2
Concomitant methotrexate or sulfasalazine may increase isoniazid hepatotoxicity risk in rheumatologic disease 4, 5
Linezolid causes hepatic transaminase elevation in some patients, with 16 cases (15%) showing increased transaminases in one study, of which 13 resolved 3

Elevated hepatic transaminases occur in 0.5-2.0% of statin users in a dose-dependent manner 6
Transaminase elevation with statins does not necessarily constitute true hepatotoxicity, and progression to liver failure is exceedingly rare 6
Statins have not been shown to worsen outcomes in patients with chronic hepatitis B or C, and may actually improve transaminases in fatty liver disease 6

For transaminitis during cefoperazone therapy, continue monitoring for mild elevations (<3× upper limit of normal) but consider discontinuation for elevations >3× ULN 7
Discontinue immediately if severe hepatotoxicity occurs (AST or ALT >5× ULN and/or total bilirubin >3× ULN), and consider hepatology consultation 7
Cephalosporins have lower hepatotoxicity risk compared to sulfonamides or macrolides 7

Rare cases of increased liver transaminase levels have occurred with IL-23 inhibitors (Guselkumab, Tildrakizumab) 8
Combination with methotrexate increases infection risk, which may indirectly affect liver enzymes 8

Mild elevations (<3× ULN without symptoms) can be monitored; moderate elevations (3-5× ULN) warrant strong consideration for discontinuation 4, 7
Severe elevations (>5× ULN) or any elevation with jaundice or hepatitis symptoms require immediate drug cessation 4, 7
Monitor liver enzymes until normalization after discontinuation 7

Assuming all transaminase elevations represent true hepatotoxicity rather than benign, reversible enzyme induction 6
Failing to screen for viral hepatitis and alcohol use before attributing transaminitis solely to medications 7