Pyrazinamide
Pyrazinamide (Z)
Pyrazinamide, discovered in 1952, is one of four drugs taken as part of a standard treatment regimen to treat TB. Pyrazinamide can also be used as part of a treatment regimen to treat MDR TB, usually involving five drugs.
Pyrazimide is used in South Africa’s standard regimens for the treatment of TB and MDR TB.
Dosage:
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Adults: |
Adults with liver damage - creatine clearance < 30 ml/min: |
Children: |
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30 – 40 mg/kg daily (max dose 2500 mg) |
25 – 35 mg/kg three times per week |
30 – 40 mg/kg daily (max dose 1500) |
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Pyrazinamide should be taken daily during the two month of intensive phase of TB treatment. Pyrazinamide should be taken during the intensive and continuation phase of MDR TB treatment. |
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How it works:
Pyrazinamide is a chemically synthesised bacteriocidal antibiotic. It converts a special enzyme to an active form which inhibits the synthesis of fatty acids; this disrupts the cell membrane and disables energy production which is necessary for the survival of the TB bacteria.
Side effects:
Pyrazinamide can cause nausea, vomiting, joint pain and jaundice. Pyrazinamide is contraindicated in patients with severe liver disease.
Given the lack of safety data, pyrazinamide is not recommended by the Center for Disease Control and Prevention (CDC) during pregnancy. However, it is nevertheless routinely used during pregnancy and no significant adverse events have been reported.
Clinical evidence:
In 1957, a study compared the following 4 treatment regimens: isoniazid and pyrazinamide; isoniazid and streptomycin; PAS and streptomycin; and, isoniazid and PAS. Researchers concluded that the isoniazid and pyrazinamide combination was most effective and had the shortest time to sputum conversion. The downside of this regimen was that it had the highest rates of toxicity.1
In 1981, a review of studies of short course therapy concluded that 6 to 9 months of regimens including pyrazinamide and rifampicin were 100% effective.2 In 1982, a controlled trial of 5 different regimens containing isoniazid and rifampicin plus two of three additional medicines - streptomycin, pyrazinamide, and ethambutol - found that patients receiving regimens containing pyrazinamide were the least likely to relapse.3
In 1986, the American Thoracic Society and the CDC updated guidelines to include pyrazinamide in first line treatment regimens for TB.
Pyrazinamide has also been shown to improve prognosis in treating MDR and XDR TB in patients that are still susceptible to the medicine. However it is not recommended as one of the four main drugs used in treatment.4
Pricing (per lowest unit, i.e. single tablet or injection):
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SA Public sector (Aug 2009 – July 2011 tender) |
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Z (500 mg) |
R0.28 |
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R (150 mg)/ E (275 mg)/ H (75 mg)/ Z (400 mg) |
R0.57 SA Public sector (August 2011 – July 2013 tender) |
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Z (500 mg) |
R0.29 |
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R (150 mg)/ E (275 mg)/ H (75 mg)/ Z (400 mg) |
R0.47 |
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SA Private sector |
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Z (500 mg) |
R0.33 |
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R (150 mg)/ E (275 mg)/ H (75 mg)/ Z (400 mg) |
R0.73 |
* Private sector prices sourced on 26/07/11. Global Drug Facility prices converted to rands on 26/07/11.
* Private and public sector prices may vary between suppliers. The lowest available prices are shown here.
Advocacy issues:
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Affordable versions of pyrazinamide are available and supply is secure. Pyrazinamide is available in fixed dose combinations.
1 JA Schwartz. Comparative efficacy of the concurrent use of pyrazinamide and isoniazid with that of other forms of therapy in the treatment of pulmonary tuberculosis. Dis Chest. 1957 Oct;32(4):455-9.
2J Grosset. Studies in short-course chemotherapy for tuberculosis. Basis for short-course chemotherapy. Chest. 1981 Dec;80(6):719-20.
3 [No authors listed] Controlled trial of 4 three-times-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Second report: the results up to 24 months. Hong Kong Chest Service/British Medical Research Council. Tubercle. 1982 Jun;63(2):89-98.
4 JA Caminero et al. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis. 2010 Sep;10(9):621-9.
