Pyrazinamide (Page 2 of 3)

ADVERSE REACTIONS:

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

OVERDOSAGE:

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

DOSAGE AND ADMINISTRATION:

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 or 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 75 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 evaluation 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.

This table is taken from the CDC-American Thoracic Society joint recommendations. ⁴

Recommended Drugs for the Initial Treatment of Tuberculosis in Children and Adults

* Doses based on weight should be adjusted as weight changes. † In persons older than 60 yr of age the daily dose of streptomycin should be limited to 10 mg/kg with a maximal dose of 750 mg.
	Daily Dose *
Drug	Children	Adults
Isoniazid	10 to 20 mg/kg	5 mg/kg
Rifampin	10 to 20 mg/kg	10 mg/kg
Pyrazinamide	15 to 30 mg/kg	15 to 30 mg/kg
Streptomycin	20 to 40 mg/kg	15 mg/kg †
Ethambutol	15 to 25 mg/kg	15 to 25 mg/kg

* In persons older than 60 yr of age the daily dose of streptomycin should be limited to 10 mg/kg with a maximal dose of 750 mg.
Maximal Daily Dose in Children and Adults
Drug
Isoniazid	300 mg
Rifampin	600 mg
Pyrazinamide	2 g
Streptomycin	1 g *
Ethambutol	2.5 g

	Twice Weekly Dose
Drug	Children	Adults
Isoniazid	20 to 40 mg/kg	15 mg/kg
Rifampin	10 to 20 mg/kg	10 mg/kg
Pyrazinamide	50 to 70 mg/kg	50 to 70 mg/kg
Streptomycin	25 to 30 mg/kg	25 to 30 mg/kg
Ethambutol	50 mg/kg	50 mg/kg

Definition of abbreviations: PO = per-orally; IM = intramuscularly.

HOW SUPPLIED:

Pyrazinamide Tablets USP contain pyrazinamide 500 mg. They are supplied as white, round, scored tablets, debossed “VP/012” in containers of 60 tablets, NDC# 61748-012-06, in containers of 90 tablets, NDC# 61748-012-09, in containers of 100 tablets, NDC# 61748-012-01, in containers of 500 tablets, NDC# 61748-012-05, and in hospital unit-dose cartons of 100 tablets (in strips of 10 tablets per strip), NDC# 61748-012-11.

Storage: Store in a well-closed container at controlled room temperature 15°C to 30°C (59°F to 86°F).

Dispense in a well-closed container with a child resistant closure.

Rx only

Marketed by:

VersaPharm Incorporated

Marietta, GA 30062

Manufactured by:

MIKART, INC.

Atlanta, GA 30318

Rev. 04/01

Code 590B00