Pyrazinamide is a first-line, bactericidal antitubercular drug, essential for the intensive phase of short-course therapy for drug-susceptible tuberculosis. It is a prodrug activated by mycobacterial pyrazinamidase to pyrazinoic acid, which is particularly effective against dormant bacilli in acidic environments like macrophages and caseous lesions. Its inclusion in the standard regimen (alongside Isoniazid, Rifampicin, and Ethambutol) has reduced treatment duration from 18-24 months to 6 months. In the Indian context, it is a cornerstone of the Revised National Tuberculosis Control Programme (RNTCP), now NTEP (National Tuberculosis Elimination Programme).
Adult: Weight-based dosing as per NTEP guidelines: 40-55 kg: 1000 mg (two 500mg tablets) daily; 56-75 kg: 1500 mg (three 500mg tablets) daily; ≥76 kg: 2000 mg (four 500mg tablets) daily. Standard daily dose is 20-25 mg/kg body weight (max 2g/day). In intermittent therapy (thrice-weekly): 35 mg/kg/dose.
Note: Administer orally, once daily, preferably on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. Can be taken with food if GI upset occurs, though this may delay absorption. Tablet can be crushed if needed. Should always be administered in combination with other antitubercular drugs as prescribed.
Pyrazinamide is a prodrug. It enters Mycobacterium tuberculosis via passive diffusion. Inside the bacterial cell, it is converted by the bacterial enzyme pyrazinamidase (PZase) to the active form, pyrazinoic acid (POA). In an acidic environment (pH ~5.5), POA is protonated and diffuses out of the cell. The efflux process depletes cellular energy, or the protonated POA re-enters the cell, disrupting membrane potential and transport. This cyclical 'futile energy expenditure' leads to bacterial death, particularly effective against non-replicating, persistent bacilli.
Pregnancy: Pregnancy Category C (US FDA). Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is a component of standard WHO-recommended regimens for pregnant women with TB. Crosses the placenta. Adequate folate supplementation is advised.
Driving: Generally safe. However, patients should be cautioned about potential dizziness or malaise, especially during initial therapy.
| Rifampicin | May increase hepatotoxicity risk. Synergistic antitubercular effect. | Major |
| Isoniazid | Additive hepatotoxicity risk. Standard combination therapy. | Major |
| Probenecid / Allopurinol | Probenecid may inhibit renal excretion of pyrazinoic acid, altering levels. Allopurinol used to treat hyperuricemia but interaction not clinically significant for TB therapy. | Moderate |
| Ethionamide | Cross-resistance and additive hepatotoxicity and GI side effects. Avoid concurrent use. | Major |
| Cyclosporine | Pyrazinamide may decrease cyclosporine levels, risking transplant rejection. Monitor levels closely. | Major |
| Antidiabetic drugs (Sulfonylureas) | Pyrazinamide may impair blood glucose control. | Moderate |
| Pyridoxine | No direct interaction. Often co-prescribed with isoniazid to prevent neuropathy. | None |
Same composition (Pyrazinamide (500mg)), different brands: