pyrazinamide; PZA (Tebrazid [Canada])
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Indications
- treatment of susceptible tuberculosis (in combination)
Contraindications
Dosage
- 15-30 mg/kg up to 2000 mg PO QD
- max dose 2-3 g/day
- 50-70 mg/kg twice weekly has been used for compliance
- generally given for 2 months
Tabs: 500 mg.
Dosage adjustment in renal failure
Table
| 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
- peak serum concentrations in 2 hours after oral dose
- absorption from GI tract nearly complete
- serum concentrations 30-50 ug/mL
- penetrates most tissues, including CSF
- MIC for M. tuberculosis at pH of 5 is 20 ug/mL
- elimination 1/2life is 9-10 hours with normal renal & liver function (26 hours ESRD)
elimination via liver
elimination via kidney
1/2life = 9-10 hours
Monitor
- liver function tests (serum ALT, serum AST) baseline & periodically every 2-4 weeks[9]
Adverse effects
- not common (1-10%)
- uncommon (< 1%)
- other
- hepatotoxicity
- most important adverse effect
- most hepatotoxic of anti-tuberculosis agents[8]
- hyperuricemia
- inhibits renal tubular excretion of uric acid[10]
- associated arthralgia
- acute gouty arthritis is rare
- salicylates generally provide relief
- brown urine
- may make glycemic control more difficult in patients with diabetes mellitus[10]
- hepatotoxicity
Drug interactions
- use in combination with rifampin may increase hepatotoxicity [7]
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) of antibiotics with warfarin
Test interactions
- may interfere with test reading of urine ketostix
Mechanism of action
- bactericidal for M. tuberculosis in an acid environment
- active against organisms within macrophages
More general terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Am Thoracic Soc, Am J Respir Crit Care Med 149:1359, 1994
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 Kaiser Permanente, Northern California, Infection Control Update, 9/2000
- ↑ Journal Watch 21(19):155, 2001 MMWR Morb Mort Wkly Rep 50:733, 2001
- ↑ 7.0 7.1 7.2 Sanford Guide to antimicrobial therapy 2001
- ↑ 8.0 8.1 Prescriber's Letter 10(9):49 2003
- ↑ 9.0 9.1 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 10.2 10.3 Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015