Drug Detail

Pyrazinamide

Last Updated June 10, 2016

Trade Names

Drug Classification

Antimycobacterial nicotinamide derivative

Formulations

Indications and Pharmacology

Indication: treatment of primary tuberculosis in combination with other antituberculosis drugs.

Mechanism of action: primarily bacteriocidal in acidic media, thought to inhibit fatty acid synthesis and possibly protein synthesis.

Pharmacokinetics: well absorbed from gastrointestinal tract and widely distributed throughout body; half-life 9-10 hours, prolonged with renal or hepatic impairment. Hydrolyzed in liver to major active metabolite, pyrazinoic acid.

Dosage

Adult Dose: 20-30 mg/kg/day in single dose or fixed-dose combination regimen, maximum 2 g/day.

Taking with food may reduce gastrointestinal adverse effects.

Use in Renal or Hepatic Insufficiency: Renal impairment: use dose at lower end of range; for glomerular filtration rate < 10 mL/min, reduce dose by up to 50%.

Contraindicated in patients with severe hepatic damage or porphyria; no adjustment needed for hepatic insufficiency.

Use in Pregnancy and Breastfeeding: Pregnancy Category C. Excreted in breast milk; no reported effects on nursing infants.

Use in Children: 30-40 mg/kg/day in single dose or fixed-dose combination regimen, maximum 2 g/day.

Warnings

Contraindicated in patients with severe hepatic damage or porphyria.

Use with caution in patients with gout, diabetes, renal impairment, or those with hypersensitivity to pyrazinamide, isoniazid, ethionamide, niacin.

Serum uric acid levels and liver function should be monitored closely since pyrazinamide renal excretion of urates.

Drug–Drug Interactions

Antigout medications (eg, allopurinol, probenecid): may require dose adjustments due to pyrazinamide inhibition of urate clearance.

Ethambutol, diuretics: additive potential for elevated serum urate levels.

Considerations for Special Populations

Use with caution in patients with gout, diabetes, renal impairment, or those with hypersensitivity to pyrazinamide, isoniazid, ethionamide, niacin.

Adverse Effects

Hepatotoxicity (especially at higher doses) including overt toxic hepatitis, hyperuricaemia associated with nongouty arthralgia, acute gout, gastrointestinal effects (nausea, anorexia, vomiting), hypersensitivity reactions (flushing, pruritus, skin rashes); rarely photosensitivity, thrombocytopenia, or sideroblastic anaemia.