Adverse effects
The most common (roughly 1%) side effect of pyrazinamide is joint pains (arthralgia), but this is not usually so severe that patients need to stop taking it. Pyrazinamide can precipitate gout flares by decreasing renal excretion of uric acid.The most dangerous side effect of pyrazinamide is hepatotoxicity, which is dose-related. The old dose for pyrazinamide was 40–70 mg/kg daily and the incidence of drug-induced hepatitis has fallen significantly since the recommended dose has been reduced to 12–30 mg/kg daily. In the standard four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol), pyrazinamide is the most common cause of drug-induced hepatitis. It is not possible to clinically distinguish pyrazinamide-induced hepatitis from hepatitis caused by isoniazid or rifampicin; test dosing is required (this is discussed in detail in tuberculosis treatment)Other side effects include nausea and vomiting, anorexia, sideroblastic anemia, skin rash, urticaria, pruritus, dysuria, interstitial nephritis, malaise, rarely porphyria, and fever. Pharmacokinetics
Pyrazinamide is well absorbed orally. It crosses inflamed meninges and is an essential part of the treatment of tuberculous meningitis. It is metabolised by the liver and the metabolic products are excreted by the kidneys. Pyrazinamide is routinely used in pregnancy in the UK and the rest of the world;  the World Health Organization (WHO) recommends its use in pregnancy; and  extensive clinical experience shows that it is safe. In the US, pyrazinamide is not used in pregnancy, citing insufficient evidence of safety. Pyrazinamide is removed by haemodialysis, so doses should always be given at the end of a dialysis session.
Resistance
Mutations in the pncA gene of M. tuberculosis, which encodes a pyrazinamidase and converts pyrazinamide to its active form pyrazinoic acid, are responsible for the majority of pyrazinamide resistance in M. tuberculosis strains. A few pyrazinamide-resistant strains with mutations in the rpsA gene have also been identified. However, a direct association between these rpsA mutations and pyrazinamide resistance has not been established. The pyrazinamide-resistant M. tuberculosis strain DHMH444, which harbors a mutation in the carboxy terminal coding region of rpsA, is fully susceptible to pyrazinoic acid and pyrazinamide resistance of this strain was previously associated with decreased pyrazinamidase activity. Further, this strain was found to be susceptible to pyrazinamide in a mouse model of tuberculosis. Thus, current data indicate that rpsA mutations are not likely to be associated with pyrazinamide resistance. Currently, three main methods of testing are used for pyrazinamide resistance: 1) phenotypic tests where a tuberculosis strain is grown in the presence of increasing concentrations of pyrazinamide, 2) measuring levels of pyrazinamidase enzyme produced by the tuberculosis strain, or 3) looking for mutations in the pncA gene of tuberculosis. Concerns exist that the most widely used method for phenotypic resistance testing may overestimate the number of resistant strains.Global resistance of tuberculosis to pyrazinamide has been estimated to be in 16% of all cases, and 60% of people with multidrug-resistant tuberculosis. Abbreviations
The abbreviations PZA and Z are standard, and used commonly in the medical literature, although best practice discourages the abbreviating of drug names to prevent mistakes.