Pyrazinamide Drug Information

Pyrazinamide should always be administered with other effective antituberculous drugs. It is administered for the initial 2 months of a 6-month or longer treatment regimen for drug-susceptible patients. Patients who are known or suspected to have drug-resistant disease should be treated with regimens individualized to their situation.

Pyrazinamide frequently will be an important component of such therapy. Patients with concomitant HIV infection may require longer courses of therapy. Physicians treating such patients should be alert to any revised recommendations from CDC for this group of patients.

Usual dose: Pyrazinamide is administered orally, 15 to 30 mg/kg once daily. Older regimens employed 3 to 4 divided doses daily, but most current recommendations are for once a day. Three grams per day should not be exceeded.

The CDC recommendations do not exceed 2 g per day when given as a daily regimen (see table). Alternatively, a twice weekly dosing regimen (50 to 70 mg/kg twice weekly based on lean body weight) has been developed to promote patient compliance with a regimen on an outpatient basis. In studies evaluating the twice weekly regimen, doses of pyrazinamide in excess of 3 g twice weekly have been administered.

This exceeds the recommended maximum 3 g/daily dose. However, an increased incidence of adverse reactions has not been reported. The table is taken from the CDC-American Thoracic Society joint recommendations: 4 Recommended Drugs for the Initial Treatment of Tuberculosis in Definition of abbreviations: PO = perorally; IM = intramuscularly. Doses based on weight should be adjusted as weight changes. *In persons older than 60 yrs of age the daily dose of streptomycin should be limited to 10 mg/kg with a maximal dose of 750 mg.

General Fever, porphyria and dysuria have rarely been reported. Gout (see PRECAUTIONS ). Gastrointestinal The principal adverse effect is a hepatic reaction (see WARNINGS ).

Hepatotoxicity appears to be dose related, and may appear at any time during therapy. GI disturbances including nausea, vomiting and anorexia have also been reported. Hematologic and Lymphatic Thrombocytopenia and sideroblastic anemia with erythroid hyperplasia, vacuolation of erythrocytes and increased serum iron concentration have occurred rarely with this drug.

Adverse effects on blood clotting mechanisms have also been rarely reported. Other Mild arthralgia and myalgia have been reported frequently. Hypersensitivity reactions including rashes, urticaria, and pruritus have been reported.

Fever, acne, photosensitivity, porphyria, dysuria and interstitial nephritis have been reported rarely.

Teratogenic Effects – Pregnancy Category C Animal reproduction studies have not been conducted with pyrazinamide. It is also not known whether pyrazinamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pyrazinamide should be given to a pregnant woman only if clearly needed.

Pyrazinamide regimens employed in adults are probably equally effective in pediatric patients. 4, 10, 11 Pyrazinamide appears to be well tolerated in pediatric patients.

Pyrazinamide is contraindicated in persons: with severe hepatic damage. who have shown hypersensitivity to it. with acute gout.

Overdosage experience is limited. In one case report of overdose, abnormal liver function tests developed. These spontaneously reverted to normal when the drug was stopped.

Clinical monitoring and supportive therapy should be employed. Pyrazinamide is dialyzable. 13