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pyrazinamide; PZA (Tebrazid [Canada])

Indications: - treatment of susceptible tuberculosis (in combination) Contraindications: - active gout - caution in patients with history of gout [10] Dosage: 1) 15-30 mg/kg up to 2000 mg PO QD 2) max dose 2-3 g/day 3) 50-70 mg/kg twice weekly has been used for compliance 4) generally given for 2 months Tabs: 500 mg. Dosage adjustment in renal failure: creatinine clearance dosage [7] > 50-90 mL/min 25 mg/kg every 24 hours 10-50 mL/min 25 mg/kg every 24 hours < 10 mL/min* 12-25 mg/kg every 24 hours * 40 mg/kg 24 hours prior to each 3 times/week hemodialysis # no dose adjustment (with or without dialysis) [5] Pharmacokinetics: 1) peak serum concentrations in 2 hours after oral dose 2) absorption from GI tract nearly complete 3) serum concentrations 30-50 ug/mL 4) penetrates most tissues, including CSF 5) MIC for M. tuberculosis at pH of 5 is 20 ug/mL 6) elimination 1/2life is 9-10 hours with normal renal & liver function (26 hours ESRD) Monitor: - liver function tests (serum ALT, serum AST) baseline & periodically every 2-4 weeks [9] Adverse effects: 1) not common (1-10%) - arthralgia, myalgia, nausea/vomiting, anorexia 2) uncommon (< 1%) - rash, itching, gout*, hepatotoxicity, fever, acne, photosensitivity, porphyria, dysuria, interstitial nephritis, thrombocytopenia 3) other a) hepatotoxicity - most important adverse effect - most hepatotoxic of anti-tuberculosis agents [8] b) hyperuricemia - inhibits renal tubular excretion of uric acid [10] - associated arthralgia - acute gouty arthritis is rare - salicylates generally provide relief c) brown urine d) may make glycemic control more difficult in patients with diabetes mellitus [10] Drug interactions: -> use in combination with rifampin may increase hepatotoxicity [7] Test interactions: - may interfere with test reading of urine ketostix Mechanism of action: 1) bactericidal for M. tuberculosis in an acid environment 2) active against organisms within macrophages

Interactions

drug interactions

General

anti-tuberculous agent

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 9-10 HOURS

Database Correlations

PUBCHEM cid=1046

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Am Thoracic Soc, Am J Respir Crit Care Med 149:1359, 1994
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Kaiser Permanente, Northern California, Infection Control Update, 9/2000
  6. Journal Watch 21(19):155, 2001 MMWR Morb Mort Wkly Rep 50:733, 2001
  7. Sanford Guide to antimicrobial therapy 2001
  8. Prescriber's Letter 10(9):49 2003
  9. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  10. Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015

Component-of

isoniazid/pyrazinamide/rifampin (Rifater)