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 Zambia HIV National Guidelines
 


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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antimicrobial Agents>
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Pyrazinamide

Paul A. Pham Pharm.D. and John G. Bartlett M.D.
09-30-2009

Zambia Specific Information

  • Available formulation in Zambia: Pyrazinamide tablet: 400 mg. Tablet (dispersible): 150 mg. Tablet (scored): 150 mg. Rifampicin + isoniazid + pyrazinamide tablet: 60 mg + 30 mg + 150 mg; 150 mg + 75 mg + 400 mg. 150 mg + 150 mg + 500 mg (For intermittent use 3 times weekly). Rifampicin + isoniazid + pyrazinamide + ethambutoltablet: 150 mg + 75 mg + 400 mg + 275 mg.
  • All new TB cases (smear positive, smear negative, extra-pulmonary TB, and smear negative relapse): INH, RIF, PZA, and EMB x 2 months, then INH plus EMB x 6 months.
  • TB smear positive re-treatment cases (e.g treatment failure, treatment after default, smear positive relapse): INH, RIF, PZA, EMB, and SM x 2 months, then INH, RIF, PZA, and EMB x 6 months.
  • MDRTB standardized regimen: pyrazinamide 1000 mg/d (<50kg); 1500 mg (50-65kg); 2000 mg (>65kg) plus ethionamide, kanamycin, ofloxacin, and ethambutol x 4 month, then based on culture conversion and sensitivity, continue with ethionamide, ofloxacin, and ethambutol for 12-18 months.
Zambia Information Author: Paul A. Pham, Pharm. D.

INDICATIONS

FDA

  • TB (active, latent) treatment (in combination with other antituberculous drugs)

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
PyrazinamidePyrazinamide (PZA)Several generic manufacturers (Stada, UD, and others)oral
tablet
500mg
$1.19
Rifater PZA 300 mg/isoniazid (INH) 50 mg/rifampin (RIF) 120 mgAventisoral
capsule
PZA300mg/ INH 50mg / RIF 120 mg
$1.92

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

  • Active TB (induction phase): 20-25mg/kg (max 2gm) once-daily in combination with RIF, ethambutol(EMB), and INH x 8 wks
  • DOT active TB treatment (in combination with RIF + EMB + INH): 40-55kg: 1500mg 3x/wk or 2000mg 2x/wk; 56-75kg: 2500 mg 3x/wk or 3000mg 2x/wk; 76-90kg: 3000mg 3x/wk or 4000mg 2x/wk. MAX DOSE: 2000mg/d; 3000mg 3x/wk; 4000mg 2x/wk.
  • Pts with CD4 <100 should receive once-daily or 3x/wk therapy for active TB.
  • PZA + RIF x 2 mos for treatment of latent TBno longer recommended by the CDC due to hepatotoxicity; however, a subsequent analysis showed no deaths or serious reactions among the 792 HIV+-infected pts who took RIF/PZA; the rate of AST >250 U/l at 2 mos was 2.1% (CID 2004; 39: 561)
  • Treatment with Rifater: wgt. <65 kg 1 tab/10 kg/d; > 65 kg 6 tabs/d

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

12-20 mg/kg/d. Risk of hyperuricemia may be increased; HD: usual dose post-HD on days of HD.

DOSING IN HEMODIALYSIS

HD: usual dose post-HD on days of HD. Risk of hyperuricemia may be increased

DOSING IN PERITONEAL DIALYSIS

No data, Avoid

DOSING IN HEMOFILTRATION

No data

ADVERSE DRUG REACTIONS

For Rifater ADRs see also INH and RIF

COMMON

  • Non-gouty polyarthralgia (up to 40%, Rx with ASA)
  • Asymptomatic hyperuricemia
OCCASIONAL

  • Dose related hepatitis (1% at 25mg/kg, but up to 15% with >3gm/day). Monitor for Sx suggestive of hepatitis at baselineand 2, 4, 6, and 8 wks. Bilirubin, AST, and ALT at baseline and 2, 4, and 6 wks. D/C if LFTs >5 xULN in asymptomatic pt or at any level above normal range in symptomatic pt. Risk increased with alcohol consumption.
  • GI intolerance.
RARE

  • Gout (Rx w/ allopurinol and probenecid). D/C and do not restart if hyperuricemia accompanied by acute gouty arthritis..

DRUG INTERACTIONS

For Rifater Drug Interactions see also INHand RIF

SPECTRUM

M. kansasiiintrinsically resistant to PZA.

Detailed Spectrum of Activity

PHARMACOLOGY

Pharmacology

COMMENTS

1st line agent in combination with other antituberculous drugs for TB treatment. Monitor LFTs closely with RIF co-administration; use with caution in pts with gout due to potential for PZA-induced hyperuricemia.

REFERENCES

REFERENCED WITHIN THIS GUIDE


 
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