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Pyrazinamide ball-and-stick.png
Clinical data
Trade names Rifater, Tebrazid, others[1]
AHFS/ Monograph
MedlinePlus a682402
Routes of
by mouth
ATC code
Pharmacokinetic data
Bioavailability >90%
Metabolism liver
Biological half-life 9 to 10 hours
Excretion kidney
CAS Number
PubChem CID
ECHA InfoCard 100.002.470
Chemical and physical data
Formula C5H5N3O
Molar mass 123.113 g/mol
3D model (Jmol)

Pyrazinamide is a medication used to treat tuberculosis.[2] For active tuberculosis it is often used together with rifampin, isoniazid, and either streptomycin or ethambutol.[3] It is not generally recommended for the treatment of latent tuberculosis.[2] It is taken by mouth.[1]

Common side effects include nausea, loss of appetite, muscle pains, and rash. More serious side effects include gout, liver toxicity, and sensitivity to sunlight.[2] It is not recommended in those with significant liver disease or porphyria. It is unclear if use during pregnancy is safe but it is likely okay during breastfeeding.[3] Pyrazinamide is in the antimycobacterial class of medications. It is not entirely clear how it works.[2]

Pyrazinamide was first made in 1936 but did not come into wide use until 1972.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] Pyrazinamide is available as a generic medication.[2] The wholesale cost in the developing world is about 2.76 USD per month.[6] In the United States it costs about 100 to 200 USD per month.[1]

Medical uses[edit]

Pyrazinamide is only used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis. It is never used on its own. It has no other indicated medical uses. In particular, it is not used to treat other mycobacteria; Mycobacterium bovis and Mycobacterium leprae are innately resistant to pyrazinamide.

Pyrazinamide is used in the first two months of treatment to reduce the duration of treatment required.[7] Regimens not containing pyrazinamide must be taken for nine months or more.

Pyrazinamide is a potent antiuricosuric drug[8] and consequently has an off-label use in the diagnosis of causes of hypouricemia and hyperuricosuria.[9] It acts on URAT1.[9]

Adverse effects[edit]

The most common (approximately 1%) side effect of pyrazinamide is joint pains (arthralgia), but this is not usually so severe that patients need to stop taking the pyrazinamide.[10][11] Pyrazinamide can precipitate gout flares by decreasing renal excretion of uric acid.[12]

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. In the standard four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol), pyrazinamide is the most common cause of drug-induced hepatitis.[13] 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.


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 WHO recommend its use in pregnancy; and there is extensive clinical experience to show that it is safe. In the U.S., pyrazinamide is not used in pregnancy, citing insufficient evidence of safety.[14] Pyrazinamide is removed by haemodialysis and therefore doses should always be given at the end of a dialysis session.

Mechanism of action[edit]

Pyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis.

Pyrazinamide diffuses into the granuloma of M. tuberculosis, where the tuberculosis enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid.[15] Under acidic conditions of pH 5 to 6, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH.[15][16]

Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids[17] although this has been discounted.[18][19] It was also suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid also binds to the ribosomal protein S1 (RpsA) and inhibits trans-translation, which may explain the ability of the drug to kill dormant mycobacteria.[20]


Mutations in the pncA gene of tuberculosis, which encodes a pyrazinamidase and converts pyrazinamide to its active form, is responsible for the appearance of most pyrazinamide resistant M. tuberculosis strains.[21] A few pyrazinamidase resistant strains with mutations in the rpsA gene have also been identified.[20] There are currently three main methods of testing 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.[15] There have been concerns that the most widely used method for phenotypic resistance testing may overestimate the amount of resistant strains.[22][23]

Global resistance of tuberculosis to pyrazinamide has been estimated to be in 16% of all cases, and 60% of people with multidrug-resistant tuberculosis.[15]


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.


Pyrazinamide is a generic drug, and is available in a wide variety of presentations. Pyrazinamide tablets form the bulkiest part of the standard tuberculosis treatment regimen. Pyrazinamide tablets are so large, some people find them impossible to swallow: pyrazinamide syrup is an option.

Pyrazinamide is also available as part of fixed-dose combinations with other TB drugs such as isoniazid and rifampicin (Rifater is an example).


Pyrazinamide was first discovered and patented in 1936 but not used against tuberculosis until 1952.[19] Its discovery as an anti-tubercular agent was remarkable since it has no activity against tuberculosis in-vitro, due to not being active at a neutral pH, so would ordinarily not be expected to work in-vivo.[24] However, it was known that nicotinamide had activity against tuberculosis and pyrazinamide was thought to have a similar effect. Experiments in mice at Lederle and Merck confirmed its ability to kill tuberculosis and it was rapidly used in humans.[24]


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