Pyrazinamide

Indications

Pyrazinamide is used for: Tuberculosis

Adult Dose

Oral Tuberculosis Adult: As part of a multidrug regimen: For standard unsupervised 2-mth treatment: <50 kg: 1.5 g daily; >50 kg: 2 g daily. For intermittent supervised 2-mth treatment: <50 kg: 2 g 3 times wkly; >50 kg: 2.5 g 3 times wkly. Hepatic impairment: Severe: Contraindicated.

Child Dose

Oral Tuberculosis Child: As part of a multidrug regimen: For standard unsupervised 2-mth treatment: 35 mg/kg daily. For intermittent supervised 2-mth treatment: 50 mg/kg 3 times wkly.

Renal Dose

Renal impairment: May need dose reduction.

Administration

Should be taken with food.

Contra Indications

Hypersensitivity; existing liver disease; acute gout or hyperuricaemia. Porphyria. Pregnancy and lactation.

Precautions

Patient w/ DM, history of gout. Mild to moderate hepatic and renal impairment. Pregnancy and lactation. Monitoring Parameters Monitor liver function, serum uric acid, sputum culture; chest x-ray 2-3 mth into treatment and at completion.

Pregnancy-Lactation

Pregnancy Category: C Lactation: enters breast milk

Interactions

Antagonises the effect of uricosuric agents (e.g. probenecid, sulfinpyrazone). May reduce the contraceptive effect of oestrogens. May inactivate oral typhoid vaccine. May increase the serum concentration of ciclosporin. May enhance the hepatotoxic effect of rifampicin.

Adverse Effects

Side effects of Pyrazinamide : 1-10% Malaise, Nausea, Vomiting, Anorexia, Arthralgia, Myalgia <1% Fever, Rash, Itching, Acne, Photosensitivity, Gout, Dysuria, Porphyria, Thrombocytopenia, Hepatotoxicity, Interstitial nephritis Potentially Fatal: Severe liver damage, fulminant hepatitis.

Mechanism of Action

Pyrazinamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of the infection and the susceptibility of the infecting organism. Its activity appears to partly depend on conversion of the drug to pyrazinoic acid (POA), which lowers the pH of the environment below that which is necessary for growth of Mycobacterium tuberculosis. Susceptible strains of M. tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to POA, and the in vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity.