Pyrazinamide (PDF Version)

Antibiotic Class:

Pyrazinoic acid amide (carboxyamide-2-pyrazine)

 

Antimicrobial Spectrum:

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.

 

Pharmacodynamics:

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.

 

Pharmacokinetics:

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.

 

Adverse Effects:

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.

 

Dosage:

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.

 

Drug Interactions:

No known interactions based on clearance.

 

Pregnancy:

Use with caution as indicated.

 

Monitoring Requirements:

Toxic: baseline liver enzymes, with periodic testing during treatment.