Adult: As part of a mulitdrug regimen: For standard unsupervised 2-mth treatment: <50 kg: 1.5 g daily; ≥50 kg: 2 g daily. For intermittent supervised 2-mth treatment: <50 kg: 2 g 3 times wkly; ≥50 kg: 2.5 g 3 times wkly. Child: As part of a mulitdrug regimen: For standard unsupervised 2-mth treatment: 35 mg/kg daily. For intermittent supervised 2-mth treatment: 50 mg/kg 3 times wkly.
Renal Impairment
May need dose reduction.
Hepatic Impairment
Severe: Contraindicated.
Administration
Should be taken with food.
Contraindications
Hypersensitivity. Hyperuricaemia and/or gouty arthritis, acute porphyria. Severe hepatic impairment.
Special Precautions
Patient w/ DM, history of gout. Mild to moderate hepatic and renal impairment. Pregnancy and lactation.
Adverse Reactions
Hyperuricaemia, leading to acute gout; anorexia, nausea, vomiting, aggravation of peptic ulcer, arthralgia, malaise, fever, sideroblastic anaemia, thrombocytopenia, dysuria. Rarely, photosensitivity, pellagra, rash. Potentially Fatal: Hepatotoxicity.
Monitor liver function, serum uric acid, sputum culture; chest x-ray 2-3 mth into treatment and at completion.
Overdosage
Symptoms: Liver toxicity and hyperuricaemia. Management: Empty the stomach by gastric lavage if necessary. Employ general supportive measures. May give benzodiazepine if there is evidence of CNS stimulation and probenecid for hyperuricaemia.
Drug Interactions
Antagonises the effect of uricosuric agents (e.g. probenecid, sulfinpyrazone). May reduce the contraceptive effect of oestrogens. May inactivate oral typhoid vaccine. May increase the serum concentration of ciclosporin. May enhance the hepatotoxic effect of rifampicin.
Lab Interference
May interfere w/ Acetest® and Ketostix® urine tests to produce pinkish-brown color.
Action
Description: Pyrazinamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of the infection and the susceptibility of the infecting organism. Its activity appears to partly depend on conversion of the drug to pyrazinoic acid (POA), which lowers the pH of the environment below that which is necessary for growth of Mycobacterium tuberculosis. Susceptible strains of M. tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to POA, and the in vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity. Pharmacokinetics: Absorption: Readily absorbed from the GI tract. Time to peak plasma concentration: Approx 2 hr. Distribution: Widely distributed in body fluids and tissues, diffuses in the CSF and enters breast milk. Plasma protein binding: 50%. Metabolism: Undergoes hepatic metabolism via hydrolysis to pyrazinoic acid (major active metabolite) and subsequently hydroxylated to 5-hydroxypyrazinoic acid (major excretory product). Excretion: Via urine by glomerular filtration (approx 70% mainly as metabolites, approx 4% as unchanged drug). Half-life: Approx 9-10 hr.
Chemical Structure
Pyrazinamide Source: National Center for Biotechnology Information. PubChem Database. Pyrazinamide, CID=1046, https://pubchem.ncbi.nlm.nih.gov/compound/Pyrazinamide (accessed on Jan. 22, 2020)
Anon. Pyrazinamide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/08/2014.Buckingham R (ed). Pyrazinamide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/08/2014.McEvoy GK, Snow EK, Miller J et al (eds). Pyrazinamide. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 26/08/2014.Pyrazinamide Tablet (DAVA Pharmaceuticals, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 26/08/2014.
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