Pyrazinamide

Agent: pyrazinamide

Pyrazinamide is a first-line drug for the treatment of tuberculosis. It is added to the initial 4-drug regimen to shorten the overall duration of therapy from 9 months to 6 months. Pyrazinamide has bactericidal activity against even slow-growing  M. tuberculosis by inhibiting fatty acid synthesis at a different step than isoniazid does. It is generally used only in the first 2 months of tuberculosis therapy.

Spectrum

Active only against M. tuberculosis.

Adverse Effects

The key adverse effects for pyrazinamide are hyperuricemia and hepatotoxicity. Hepatotoxicity (chiefly hepatitis) is dose-dependent and less common at the lower doses given today than the higher ones previously used. Hyperuricemia is predictable and can rarely precipitate gout, leading to withdrawal of pyrazinamide from the regimen and an extension of the duration of tuberculosis therapy. Arthralgias also occur and are separate from hyperuricemia; these can be managed with over-the-counter pain medications.

Important Facts

• Interestingly, pyrazinamide is active only in acidic environments (pH  >  6). This would be problematic for some diseases, but it is perfect for the caseous granulomas that active tuberculosis forms. It also works intracellularly in phagocytes.

• Pyrazinamide is no longer used in combination with rifampin as an alternative for latent tuberculosis because of high rates of hepatitis.

• Be careful not to confuse this drug with pyridoxine, which most patients with tuberculosis should also be taking.

What It’s Good For

Pyrazinamide’s only use is in the initial phase of ac-tive tuberculosis treatment.

Don’t Forget!

Tell your patients to report any signs of hepatitis  (dark urine, abdominal pain, loss of appetite) when they are on pyrazinamide or any first-line tuberculosis therapy.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.