Hepatotoxicity of Common Medications

Introduction to Hepatotoxic Drugs

Acetaminophen, isoniazid, rifampin, and pyrazinamide are among the most common hepatotoxic drugs that can cause significant liver injury, with acetaminophen being the leading cause of drug-induced liver failure in the United States 1

Isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) are first-line antituberculosis drugs that can cause drug-induced liver injury (DILI) 2, 3
Among first-line agents for tuberculosis treatment, pyrazinamide is considered the most hepatotoxic 4

Acetaminophen is the most common cause of drug-induced liver failure and can cause fulminant hepatic failure, especially at doses exceeding 4g per day 5
Even at therapeutic doses, acetaminophen can cause hepatotoxicity in chronic alcohol users 5
Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for approximately 10% of drug-induced hepatitis cases 5
NSAIDs can cause increased side effects and toxicity in patients with liver disease due to higher concentrations of free compounds 5

Excessive alcohol consumption, even if discontinued during treatment, increases the risk of drug-induced liver injury 4
Underlying liver disease predisposes patients to drug-induced hepatotoxicity 4
Previous history of drug-induced liver injury increases the risk of recurrence with re-exposure to the same or similar drugs 4

Drug-induced hepatitis is suspected when ALT levels are ≥3 times the upper limit of normal with hepatitis symptoms, or ≥5 times the upper limit of normal without symptoms 2, 6
When hepatotoxicity is suspected, the offending drugs should be stopped immediately and the patient carefully evaluated 2, 6
Baseline and regular monitoring of liver function is required in patients with known chronic liver disease who are taking potentially hepatotoxic medications 7

In patients with liver cirrhosis, acetaminophen at doses of 2-3g per day is generally recommended instead of the standard 4g maximum 5
Patients with liver disease should avoid NSAIDs as much as possible due to increased risk of side effects including hepatotoxicity, nephrotoxicity, and gastric ulcers 5