What are common hepatotoxic (liver damaging) drugs?

Common 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, 2

First-Line Antituberculosis Drugs

• Isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) are first-line antituberculosis drugs that can cause drug-induced liver injury (DILI) 1
• Among first-line agents for tuberculosis treatment, pyrazinamide is considered the most hepatotoxic 1
• Rifampin can cause hepatotoxicity of hepatocellular, cholestatic, and mixed patterns, with severity ranging from asymptomatic elevations in liver enzymes to fulminant liver failure 3
• Isoniazid commonly causes mild hepatic dysfunction with transient elevation of serum transaminase levels in 10-20% of patients, typically within the first 1-3 months of treatment 4
• The frequency of progressive liver damage with isoniazid increases with age, occurring in up to 2.3% of patients over 50 years of age 4

Analgesics and Anti-inflammatory Drugs

• Acetaminophen is the most common cause of drug-induced liver failure and can cause fulminant hepatic failure, especially at doses exceeding 4g per day 1, 2
• Even at therapeutic doses, acetaminophen can cause hepatotoxicity in chronic alcohol users 1
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for approximately 10% of drug-induced hepatitis cases 1, 5
• NSAIDs can cause increased side effects and toxicity in patients with liver disease due to higher concentrations of free compounds 1

Other Common Hepatotoxic Medications

• Statins (HMG-CoA reductase inhibitors) have been associated with liver injury, though the frequency is lower than in the general population 5
• Antiepileptic drugs, particularly valproic acid, can cause hepatotoxicity 5, 6
• Methotrexate carries warnings about its use in patients with various liver conditions 7
• Thiazolidinediones (particularly troglitazone, which was withdrawn from the market) have been associated with liver toxicity 7, 5

Risk Factors for Drug-Induced Liver Injury

• Concurrent use of multiple hepatotoxic medications increases the risk of liver injury 6
• Excessive alcohol consumption, even if discontinued during treatment, increases the risk of drug-induced liver injury 1
• Underlying liver disease predisposes patients to drug-induced hepatotoxicity 1, 7
• Previous history of drug-induced liver injury increases the risk of recurrence with re-exposure to the same or similar drugs 1

Monitoring and Management

• 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 1
• When hepatotoxicity is suspected, the offending drugs should be stopped immediately and the patient carefully evaluated 1
• Other causes of abnormal liver function tests must be excluded before diagnosing drug-induced hepatotoxicity, including viral hepatitis, biliary tract disease, alcohol, and other hepatotoxic drugs 1
• Baseline and regular monitoring of liver function is required in patients with known chronic liver disease who are taking potentially hepatotoxic medications 1

Special Considerations

• In patients with liver cirrhosis, acetaminophen at doses of 2-3g per day is generally recommended instead of the standard 4g maximum 1
• Patients with liver disease should avoid NSAIDs as much as possible due to increased risk of side effects including hepatotoxicity, nephrotoxicity, and gastric ulcers 1
• When treating tuberculosis in patients with liver disease, careful monitoring of liver function should be done prior to therapy and then every 2-4 weeks during therapy 3
• Patients taking rifampin should be advised to abstain from alcohol, hepatotoxic medications, or herbal products 3

Drug-induced liver injury remains a significant clinical challenge, with many commonly prescribed medications carrying potential hepatotoxic effects. Early recognition of symptoms and prompt discontinuation of offending agents are essential to prevent progression to severe liver damage.