Pyrazinamide (PDF Version)
Pyrazinoic acid amide (carboxyamide-2-pyrazine)
Narrow spectrum of activity - chiefly M. tuberculosis
Mechanism of Action:
Converted to pyrazinoic acid, with (a) acts to acidify the interior of M. tuberculosis and (b) may disrupt the function of fatty acid synthase (FAS) type I.
Pyrazinamide is very difficult to test in vitro, as its activity requires a low pH, which in turn degrades the growth characteristics of M. tuberculosis. Pyrazinamide appears to show concentration-dependent activity and concentration-dependent liver toxicity.
Cmax: 20-50 mg/L with daily doses, up to 90 mg/L with larger twice-weekly doses; Tmax: about 2 hours; Bioavailability: not known, but likely is high; Protein binding: estimated to be low.
Gastrointestinal intolerance may occur- nausea is common and vomiting may occur. Arthralgias are common. Hepatocellular injury is possible, and appears to be dose-related (large daily dose of 50 mg per kg – no longer used – frequently caused liver enzyme elevation). The 2 drug combination of pyrazinamide and rifampin for latent TB infection (LTBI) is no longer recommended because of hepatotoxicity.
PO: 500 mg tablets
Usual dose: 25 mg/kg once daily, or 50 mg/kg 2-3 times weekly.
Disease state based dosing:
Hepatic failures: Pyrazinamide is usually avoided to prevent further liver damage.
Renal failures: Give 25 mg/kg 3 times weekly, rather than daily.
Contraindications/Warnings/Precautions: Use with caution pregnant women, although data to date are encouraging.
No known interactions based on clearance.
Use with caution as indicated.
Toxic: baseline liver enzymes, with periodic testing during treatment.