Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It is taken by mouth as oral tablets, typically dosed in adults at about 20 to 25 mg per kg once daily with a common upper daily dose of around 2 g. Pyrazinamide is a prodrug that is converted by mycobacterial pyrazinamidase to pyrazinoic acid, which is active against intracellular and semi-dormant Mycobacterium tuberculosis in acidic environments. Absorption from the gastrointestinal tract is rapid and bioavailability is high. Hepatic metabolism yields pyrazinoic acid and further hydroxylated metabolites, and renal excretion removes parent drug and metabolites, so dose adjustment and monitoring may be required in severe renal impairment. The drug has a half-life in the range of several hours in normal patients and can be prolonged with organ dysfunction. Clinically important safety considerations include hepatic enzyme elevation and hepatotoxicity, hyperuricemia with gout flares, gastrointestinal intolerance, arthralgia, and hypersensitivity reactions. Monitoring recommendations commonly include baseline and periodic liver function tests and uric acid levels during therapy, and avoiding use in patients with acute severe hepatic disease.
Parent: Pyrazinamide
Commercial batches and regulatory monographs routinely control a defined set of related compounds and impurities for pyrazinamide active pharmaceutical ingredient. Typical related compounds monitored include pyrazinoic acid, 5-hydroxy-pyrazinamide and other oxidative or hydrolytic degradation products, as well as residual solvents and elemental impurities from synthesis. Analytical control is generally performed by validated HPLC methods for related substances, GC for volatile solvents and ICP-MS or similar techniques for elemental impurities. Typical specification practice used by manufacturers and monographs sets identification and control thresholds consistent with ICH guidance, with individual specified impurities commonly limited in the low tenths of a percent and unspecified impurities controlled to low hundredths to tenths of a percent, and total impurities limited to around half a percent to one percent depending on the monograph and maximum daily dose. Exact acceptance criteria and identification thresholds vary by pharmacopoeial monograph and regulatory filing and should be confirmed from the relevant specification documentation for a given manufacturer or product.
Pyrazinamide is used as part of combination therapy for active pulmonary and some extrapulmonary tuberculosis. It is included in initial intensive-phase regimens to shorten treatment duration and to target intracellular and semi-dormant bacilli. It is not routinely used alone and is not generally recommended for latent tuberculosis infection.
Pyrazinamide is primarily associated with hyperuricemia due to reduced renal uric acid excretion, which can precipitate gout and rarely contribute to urate-related renal complications. The drug and its metabolites are renally excreted so accumulation can occur in severe renal impairment, requiring dose adjustment. Acute kidney injury directly caused by pyrazinamide is uncommon but renal function should be monitored, especially when used with other nephrotoxic drugs.
If the question refers to pyrazinamide, common adverse effects include elevated liver enzymes and hepatotoxicity, hyperuricemia and gout flares, nausea and vomiting, abdominal pain, arthralgia and rash. Severe but less common reactions include clinically significant liver injury and hypersensitivity. If the term pyrazine refers to a different chemical, toxicity and side effects differ and specific material safety data should be consulted.
Toxic effects of pyrazinamide in overdose or idiosyncratic reactions include marked hepatotoxicity, profound hyperuricemia with gout and potential urate nephropathy, gastrointestinal symptoms, and central nervous system effects at high exposures such as headache, dizziness or encephalopathy. Management of suspected toxicity requires symptomatic care, monitoring of liver and renal function and consultation with a medical toxicologist or poison control center.
