Pyrazinamide

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Pyrazinamide is a medicine used to treat tuberculosis (TB). It is an antimicrobial drug that is always given together with other TB drugs, such as isoniazid and rifampicin. It is not used to treat latent TB and is not given by itself.

How it is used
- Taken by mouth.
- Usually given during the first two months of TB treatment as part of a four-drug regimen to shorten the total treatment time. Without pyrazinamide, TB treatment typically lasts much longer.

Common and serious side effects
- Common: nausea, loss of appetite, muscle and joint pains, and rash.
- Serious: liver toxicity (hepatitis) and gout flares due to higher uric acid; some people may be sensitive to sunlight.
- It should be avoided in people with significant liver disease or porphyria.
- Pregnancy safety varies by country; many guidelines allow its use, but some places are more cautious. It is removed by dialysis, so dosing may be adjusted around dialysis sessions.

How it works
- Pyrazinamide is a prodrug. The TB bacteria convert it into an active form, pyrazinoic acid, which builds up inside the bacteria and helps kill them, especially in acidic parts of the infection. The exact way it works is not fully understood, and it may affect multiple bacterial processes.

Resistance and testing
- Most resistance comes from mutations in the pncA gene, which prevents activation of the drug.
- Some resistance has been linked to other bacterial changes, but this is less clear.
- Tests to detect resistance include growing the bacteria with the drug, measuring the enzyme that activates it, or checking the pncA gene.

Other notes
- Pyrazinamide is available as a generic drug and is included in fixed-dose TB combinations.
- It has a long history in TB treatment and is included in guidelines as an essential medicine in many parts of the world.