Pyrazinamide Disease Interactions

The use of pyrazinamide is contraindicated in patients with acute gout. Pyrazinamide inhibits the renal excretion of uric acid, which may frequently result in precipitation or exacerbation of gout. Therapy with pyrazinamide should be administered cautiously in patients with hyperuricemia or a history of gout. Serum uric acid levels should be monitored regularly, and appropriate measures (e.g., administration of uricosuric agents) taken to prevent the development of gout. If gouty arthritis occurs, pyrazinamide should be discontinued.

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The use of pyrazinamide is contraindicated in patients with severe liver damage. Pyrazinamide may cause hepatocellular injury, particularly in patients with underlying liver disease and during coadministration with other hepatotoxic agents including other antituberculous drugs such as isoniazid and rifampin. Therapy with pyrazinamide should be administered cautiously and under strict medical supervision in patients with liver disease or a history of alcoholism. Serum transaminases (ALT, AST) and bilirubin should be measured at baseline and monitored closely during therapy. Patients should be instructed to discontinue the drug promptly and seek medical attention if signs and symptoms of hepatic injury develop, including fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. To lessen the risk of hepatotoxicity, the maximum dosage should not exceed 2 g/day when treatment is administered daily or 3 g/day when administered twice weekly.

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Pyrazinamide is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from pyrazinamide due to decreased drug clearance. Dosage reductions are recommended in these patients if the drug is used.

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The half-life of pyrazinamide may be prolonged in patients with renal impairment. In addition, the drug's metabolites, at least one of which is pharmacologically active, may accumulate. Therapy with pyrazinamide should be administered cautiously in patients with renal dysfunction. Dosage adjustments may be necessary.

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The use of pyrazinamide may be associated with poor diabetic control. Patients with diabetes mellitus should be monitored more closely during therapy with pyrazinamide, and their antidiabetic regimen adjusted accordingly.

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Pyrazinamide is removed by hemodialysis and should be administered after dialysis.

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