First-line antituberculosis drug indicated for initial treatment of active tuberculosis in adults and children, always in combination with other antituberculous agents.
Also known as: PZA, Zinamide
DailyMed approved label (Pyrazinamide Tablet, ANI Pharmaceuticals; setID 262d8829-728c-48db-b89b-88d13b87e684).
DailyMed approved label (Pyrazinamide Tablet, ANI Pharmaceuticals; setID 262d8829-728c-48db-b89b-88d13b87e684).
Pyrazinamide + probenecid: pyrazinamide antagonises the uricosuric effect of probenecid.
The Prontuário Terapêutico documents in the pyrazinamide monograph (1.1.12): "Pyrazinamide antagonises the effects of probenecid and sulfinpyrazone". Pyrazinamide reduces renal uric acid excretion (a well-known, dose-dependent hyperuricaemic effect), counteracting the uricosuric effect of probenecid — which depends on increased tubular urate excretion. The clinical consequence is loss of efficacy of uricosuric treatment in gout patients undergoing antituberculosis therapy. The practical guidance is to monitor serum uric acid and gout signs (acute joint pain) in patients treated with probenecid during pyrazinamide, and consider adjusting the uricosuric or an alternative during the tuberculosis regimen.
Pyrazinamide + probenecid: pyrazinamide antagonises the uricosuric effect of probenecid.
The Prontuário Terapêutico documents in the pyrazinamide monograph (1.1.12): "Pyrazinamide antagonises the effects of probenecid and sulfinpyrazone". Pyrazinamide reduces renal uric acid excretion (hyperuricaemia), counteracting the uricosuric effect of probenecid.
Watch for gout signs (acute joint pain) in gout patients treated with probenecid.
Gout flare or symptomatic hyperuricaemia with the combination.
Monitor uric acid in patients on uricosuric treatment during pyrazinamide therapy; consider adjustment.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Pyrazinamide, 1.1.12 ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Pyrazinamide + isoniazid: increased risk of hepatotoxicity — monitor liver function.
The Prontuário Terapêutico documents in the pyrazinamide monograph that the combination with isoniazid potentiates the risk of hepatotoxicity (section 1.1.12). Both drugs are hepatotoxic — isoniazid via reactive CYP2E1/NAT2 metabolites and pyrazinamide by a dose-dependent mechanism — and the combination is the first-line tuberculosis regimen, so the additive risk is a central clinical concern in treatment. Surveillance includes monitoring of aminotransferases (baseline and periodic), especially in the first weeks and in patients with risk factors (advanced age, alcohol, prior liver disease, hepatitis B/C). In the presence of symptoms (nausea, jaundice, fatigue) or transaminase elevation, stop the hepatotoxic drugs and reassess. Tuberculosis is treatable and the regimen should not be interrupted without specialist guidance.
Pyrazinamide + isoniazid: additive hepatotoxicity — monitor liver function and signs of injury.
The Prontuário Terapêutico documents in the pyrazinamide monograph (1.1.12): "Co-administration of pyrazinamide and isoniazid increases the risk of developing hepatotoxicity". Both drugs of the tuberculosis regimen are hepatotoxic — the additive combination requires hepatic surveillance.
Monitor transaminases at baseline and periodically; stop if signs of liver injury.
Jaundice, raised transaminases or hepatitis symptoms with the combination.
Monitor liver function (transaminases, bilirubin) and hepatitis symptoms (nausea, jaundice, fatigue) during the tuberculosis regimen.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Pyrazinamide, 1.1.12 ; approved Isoniazid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=93252cc8-c8d4-401b-bde5-ca8a3b57651e
Alcohol adds hepatotoxicity to that of pyrazinamide, increasing the risk of liver injury during tuberculosis treatment.
Avoid alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Pyrazinamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=262d8829-728c-48db-b89b-88d13b87e684
Pyrazinamide can be taken with or without food; taking it with food reduces gastrointestinal discomfort (nausea).
Take with food if nausea or gastric discomfort occurs.
DailyMed/FDA (NIH/NLM) — approved Pyrazinamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=262d8829-728c-48db-b89b-88d13b87e684
Pyrazinamide inhibits renal uric acid excretion and may precipitate gout attacks in patients with hyperuricaemia or a history of gout.
Monitor uric acid and use with caution in patients with gout.
DailyMed/FDA (NIH/NLM) — approved Pyrazinamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=262d8829-728c-48db-b89b-88d13b87e684
Pyrazinamide is hepatotoxic and the risk of severe liver injury, especially in the first months of treatment, increases in patients with prior liver disease.
Monitor transaminases; stop if hepatitis symptoms occur (jaundice, nausea, abdominal pain).
DailyMed/FDA (NIH/NLM) — approved Pyrazinamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=262d8829-728c-48db-b89b-88d13b87e684
Pyrazinamide crosses the placenta; it is used to treat active tuberculosis in pregnancy, with monitoring of liver function.
Use in active tuberculosis, with transaminase monitoring; usual adult dose.
Excreted into breast milk; compatible with breastfeeding under supervision.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Pyrazinamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=262d8829-728c-48db-b89b-88d13b87e684 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 1, Drugs and Pregnancy: Should be used only in the first 2 months of treatment.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal activity against M. tuberculosis, especially against intracellular bacilli in acid medium (phagolysosomes); bacteriostatic or bactericidal depending on concentration. Active pyrazinoic acid allows shortening of the initial tuberculosis regimen.
Hepatic hydrolysis to the active metabolite pyrazinoic acid, which inhibits bacillary fatty-acid synthesis in acid medium; pyrazinoic acid is hydroxylated to the main excretory product, 5-hydroxypyrazinoic acid.
Well absorbed from the GI tract; plasma peaks within 2 hours (30–50 mcg/mL with doses of 20–25 mg/kg); wide distribution (liver, lungs, CSF — CSF concentration ~equal to plasma with inflamed meninges). Protein binding ~10%.
Hydrolyzed in the liver to pyrazinoic acid (active metabolite); ~70% of an oral dose is excreted in urine, mainly by glomerular filtration, within 24 hours.
Half-life of 9–10 hours in patients with normal renal and hepatic function; prolonged in renal or hepatic impairment.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
