Pyrazinamide

In this article, we will discuss Pyrazinamide (Overview). So, let’s get started.

Pyrazinamide

Clinical Pharmacology

Pyrazinamide is well absorbed from the GI tract and attains peak plasma concentrations within 2 hours. Plasma concentrations generally range from 30 to 50 mcg/mL with doses of 20 to 25 mg/kg. It is widely distributed in body tissues and fluids including the liver, lungs and cerebrospinal fluid (CSF). The CSF
concentration is approximately equal to concurrent steady-state plasma concentrations in patients with inflamed meninges. Pyrazinamide is approximately 10% bound to plasma proteins.

The half-life (t1/2) of pyrazinamide is 9 to 10 hours in patients with normal renal and hepatic function. The plasma half-life may be prolonged in patients with impaired renal or hepatic function. Pyrazinamide
is hydrolyzed in the liver to its major active metabolite, pyrazinoic acid. Pyrazinoic acid is hydroxylated to the main excretory product, 5-hydroxypyrazinoic acid.

Approximately 70% of an oral dose is excreted in urine, mainly by glomerular filtration within 24 hours.

Pyrazinamide may be bacteriostatic or bactericidal against Mycobacterium tuberculosis depending on the concentration of the drug attained at the site of infection. The mechanism of action is unknown. In vitro and in vivo the drug is active only at a slightly acidic pH.

Indication

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.)

(Patients with drug-resistant disease should be treated with regimens individualized to their situation. Pyrazinamide frequently will be an important component of such therapy.)

(In patients with concomitant HIV infection, the physician should be aware of current recommendations of CDC. It is possible these patients may require a longer course of treatment.)

It is also indicated after treatment failure with other primary drugs in any form of active tuberculosis. Pyrazinamide should only be used in conjunction with other effective antituberculous agents.

Dosage

Pyrazinamide 30-40 (35) mg/kg/day single daily dose up to maximum of 2 g.

Adult dose: 30–40 mg/kg once a day (maximum 2 g/d) or 50 mg/kg on alternate days or 75 mg/kg twice weekly.

Contraindications: Hepatic damage, arthralgia, gout.

(Pyzid tab 300 mg; PZA-Ciba, P-zide, pyzina, piraldina, copyrazin tabs 500 mg, 750 mg and 1000 mg, pyzin kid tab 300 mg; PZA-Ciba tab 250 mg, syrup PZA-Ciba 250 mg/5 ml).

Adverse Reactions

General
Fever, porphyria and dysuria have rarely been reported. Gout

Gastrointestinal
The principal adverse effect is a hepatic reaction. 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 orte Fever, acne, photosensitivity, porphyria, dysuria and interstitial nephritis have been reported rarely.

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