pyrazinamide

Pyrazinamide is an antimicrobial used in first-line therapy for active tuberculosis. It is typically given with isoniazid, rifampin, and ethambutol during the initial intensive phase.

It is a prodrug converted by Mycobacterium tuberculosis to pyrazinoic acid via the enzyme pyrazinamidase. The drug is most active at acidic pH and kills semi-dormant bacilli in granulomas, complementing other first-line drugs.

Pharmacokinetics: taken orally with good absorption. It is metabolized in the liver to pyrazinoic acid and excreted by the kidneys. The elimination half-life is about 9–11 hours and may be prolonged in liver disease.

Clinical use: standard regimens include a two-month intensive phase with isoniazid, rifampin, pyrazinamide, and ethambutol, followed by a continuation phase with isoniazid and rifampin. Pyrazinamide is not routinely used for latent TB or most resistant forms without specialist guidance.

Safety: common adverse effects are hepatotoxicity and hyperuricemia, which can cause gout. Other effects include nausea and rash. Liver function and uric acid levels are monitored. It is contraindicated in significant hepatic impairment; alcohol increases hepatotoxic risk.

Resistance typically results from mutations in the pncA gene encoding pyrazinamidase.

Pregnancy: generally considered safe to use as part of recommended TB regimens under medical supervision.