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Pyrazinamide

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Pyrazinamide, PZA

  • See Also
  1. Active Tuberculosis
  • Indications
  1. Active Tuberculosis
  2. Latent Tuberculosis (no longer recommended due to hepatotoxicity risk)
    1. Previously used in combination with Rifampin for Latent Tb
  • Mechanism
  1. Pyrazinamide is a prodrug that is metabolized into the active pyrazinoic acid via Bacterial pyrazinamidase enzyme
  2. Synthetic pyrazinoic acid amide derivative that is bactericidal against intracellular bacilli
  1. Used as part of multi-drug Active Tuberculosis Treatment regimen
  2. Child: 15 to 30 mg/kg (up to 2000 mg) orally daily
  3. Adult: 20 to 25 mg/kg orally daily based on estimated Lean Body Mass
    1. Weight 40 to 55 kg: Give 1000 mg orally daily
    2. Weight 56 to 75 kg: Give 1500 mg orally daily
    3. Weight 76 to 90 kg: Give 2000 mg orally daily
    4. Weight >90 kg: Give 2000 mg orally daily and consider monitoring serum drug levels for adequate dosing
    5. Maximum Dose: 2000 mg
  • Adverse Effects
  1. Drug-Induced Hepatitis or Hepatotoxicity
  2. Gastrointestinal upset
  3. Transient Morbiliform Rash
  4. Arthralgias (unrelated to gout)
  5. Hyperuricemia (or Acute Gout)
  • Safety
  1. Pregnancy Category C
  2. Considered safe in Lactation
  • Monitoring
  1. Baseline
    1. Liver Function Tests (LFT)
    2. Serum Creatinine
      1. Consider reducing dose in renal dysfunction
  2. Periodic LFT testing
    1. Liver Function Tests repeated 1-2 times monthly if risks for hepatotoxicity
      1. Stop if LFTs >3x baseline if sympomatic (>5x baseline if asymptomatic)
    2. Indications for Liver Function Test monitoring
      1. Abnormal baseline Liver Function Test
      2. History suggestive of Possible liver disorder
      3. Human Immunodeficiency Virus (HIV)
      4. Pregnancy
      5. Postpartum (within 3 months)
      6. Chronic Liver Disease
        1. Viral Hepatitis (Hepatitis B or Hepatitis C)
        2. Alcoholic Hepatitis
        3. Cirrhosis
  3. Other testing
    1. Serum Uric Acid if symptoms related to gout
  • Resources
  1. Pyrazinamide (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ecee3128-a47f-4ced-a1db-4f58c5f3e9c6
  • References
  1. (2019) Presc Lett, Resource #350309, Tuberculosis Treatment in Adults: FAQ
  2. (2012) Med Lett Drugs Ther 10(116): 29-36