Pyrazinamide

Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents. (The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. *4 ) (Patients with drug-resistant disease should be treated with regimens individualized to their situation. …

• 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

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

Clinical studies of pyrazinamide did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. …

• Patients should be instructed to notify their physicians promptly if they experience any of the following: fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, pain or swelling of the joints
• Compliance with the full course of therapy must be emphasized, and the importance of not missing any doses must be stressed

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

Patients started on pyrazinamide should have baseline serum uric acid and liver function determinations. Those patients with preexisting liver disease or those at increased risk for drug related hepatitis (e.g., alcohol abusers) should be followed closely. Pyrazinamide should be discontinued and not be resumed if signs of hepatocellular damage or hyperuricemia accompanied by an acute gouty arthritis appear.

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. …

PREGNANCY 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.

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

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.