Hepatotoxicity of Anti-TB Drugs

Introduction to Hepatotoxicity

• The CDC explicitly states that among first-line agents in the treatment of active TB disease, pyrazinamide (PZA) is the most hepatotoxic, leading to major guideline revisions in 2003 when the CDC and American Thoracic Society recommended against using rifampin-pyrazinamide (RZ) regimens for latent TB infection due to unacceptably high rates of severe liver injury and death 1
• Pyrazinamide-containing regimens were specifically excluded from WHO and European Respiratory Society treatment recommendations because of high documented toxicity 3

Patient Selection and Monitoring

• The 2-month rifampin-pyrazinamide regimen for latent TB should never be offered to patients who are taking other hepatotoxic medications, drink excessive alcohol, have underlying liver disease, or have a history of isoniazid-associated liver injury 1, 2
• If pyrazinamide must be used, patients require intensive monitoring, including baseline liver function tests, monitoring at 2, 4, 6, and 8 weeks, and immediate discontinuation if ALT >5× upper limit of normal (asymptomatic) or >3× with symptoms 1, 2