Pyrazinamide, the pyrazine analogue of nicotinamide, is an antituberculous agent.
Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents. (The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months.* 4)
(Patients with drug-resistant disease should be treated with regimens individualized to their situation. Pyrazinamide frequently will be an important component of such therapy.)
(In patients with concomitant HIV infection, the physician should be aware of current recommendations of CDC. It is possible these patients may require a longer course of treatment.)
It is also indicated after treatment failure with other primary drugs in any form of active tuberculosis.
Pyrazinamide should only be used in conjunction with other effective antituberculous agents.
*See recommendations of Center for Disease Control (CDC) and American Thoracic Society for complete regimen and dosage recommendations. 4
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Published Studies Related to Pyrazinamide
14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and
moxifloxacin combinations: a randomised trial. 
first 14 days of treatment to assess their suitability for future development... INTERPRETATION: PA-824-moxifloxacin-pyrazinamide is potentially suitable for
Pyrazinamide blood concentrations in children suffering from tuberculosis: a comparative study at two doses. [2008.03]
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Pyrazinamide is recommended in doses varying from 15 to 40 mg kg(-1). The most commonly used average daily dose is 25 mg kg(-1). Its use is associated with dose dependent hepatotoxicity. Lower doses are not used because of lack of pharmacokinetic data especially in children. There is only one detailed study of pyrazinamide in children at a dose of 35 mg kg(-1). WHAT THIS STUDY ADDS: This is the first study evaluating serum concentrations of pyrazinamide in children at a dose of 15 mg kg(-1) which is on the lower side of the recommended dose. The study also compared the serum concentrations and pharmacokinetics achieved with this dose with the widely used dose of 25 mg kg(-1) in children suffering from tuberculosis. The pharmacokinetics and pharmacodynamic indices of pyrazinamide were comparable with the 25 and 15 mg kg(-1) doses. AIMS: To evaluate the pharmacokinetics and pharmacodynamic indices of pyrazinamide at doses of 15 and 25 mg kg(-1) in children suffering from tuberculosis... CONCLUSIONS: The study indicates that comparable serum concentrations of pyrazinamide are attained with 25 mg kg(-1) and 15 mg kg(-1) doses in children. The elimination half-life was longer and volume of distribution greater in children than in the adult population.
Biological evaluation of pyrazinamide liposomes for treatment of Mycobacterium tuberculosis. [2007.02.07]
Pyrazinamide liposomes were prepared employing the phospholipid molar ratios; dipalmitoyl phosphatidyl choline (7):cholesterol (2) neutral and dipalmitoyl phosphatidyl choline (7):cholesterol (2):dicetyl phosphate (1) negatively charged. Swelling at 52 degrees C led to higher trapping efficiencies...
Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. [2006.04.15]
RATIONALE: Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies. OBJECTIVES: To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil... CONCLUSIONS: Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.
Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus? [2005.03]
SETTING: Nine public health care centres in four Spanish cities. OBJECTIVE: To evaluate the efficacy and safety of 2 months of rifampicin (R) plus pyrazinamide (Z) therapy (2RZ) compared with a 6-month course of isoniazid therapy (6H) for treating latent tuberculosis infection (LTBI).We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible.
Clinical Trials Related to Pyrazinamide
Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide [Recruiting]
Multidrug resistant tuberculosis (MDR-TB) is difficult to treat and raises a great challenge
to TB control program. That pyrazinamide can shorten the course of treatment and facilitate
bacilli clearance has been proved recently. In 2011, WHO recommended to use pyrazinamide
throughout the course of treatment for MDR-TB. However, pyrazinamide susceptibility testing
has not been widely used in clinic. And the conventional testing is time-consuming and
unreliable. In contrast, the detection of pncA and rpsA mutations with molecular methods can
provide rapid results of pyrazinamide susceptibility. The purpose of this study is to
evaluate the efficacy of the introduce the molecular testing of pyrazinamide susceptibility
in optimizing the MDR-TB treatment regimen.
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) [Active, not recruiting]
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral
administration of TMC207 plus PA-824 plus Pyrazinamide plus Clofazimine, TMC207 plus PA-824
plus Pyrazinamide, TMC207 plus PA-824 plus Clofazimine alone, TMC207 plus Pyrazinamide plus
Clofazimine, Pyrazinamide alone, Clofazimine alone, and standard first line TB treatment as
per South African TB Guidelines (Rifafour e-275) as determined by the rate of change of log
CFU per ml sputum over the time period Day 0-14 in participants with smear positive
pulmonary tuberculosis (TB). A control group will receive standard treatment.
A Bioequivalence Study Comparing A Fixed Dose Combination Formulation Of Myrin P Forte That Contains Rifampicin, Isoniazid, Ethambutol And Pyrazinamide Per Tablet To An Equivalent Dose Of Single Drug Reference Preparations Of Similar Combination Following Oral Administration In Healthy Adults [Completed]
Shortening Treatment by Advancing Novel Drugs [Recruiting]
The purpose of this study is to assess the efficacy, safety and tolerability of a
combination of moxifloxacin, PA-824, and pyrazinamide treatments with varying doses and
treatment lengths from 4 to 6 months in subjects with drug-sensitive (DS) pulmonary TB
compared to standard HRZE treatment.
This study will also assess the efficacy, safety and tolerability of a combination of
moxifloxacin, PA-824, and pyrazinamide treatments after 6 months of treatment in subjects
with multi drug-resistant (MDR) pulmonary TB compared to a combination of moxifloxacin,
PA-824, and pyrazinamide treatments in DS-TB subjects.
A Phase 2 Open Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of Combinations of Bedaquiline, Moxifloxacin, PA-824 and Pyrazinamide in Adult Subjects With Drug-Sensitive or Multi Drug-Resistant Pulmonary Tuberculosis. [Recruiting]
The purpose of this study is to determine the mycobactericidal activity of combinations of
bedaquiline (J), moxifloxacin (M), PA-824 (Pa) and pyrazinamide (Z) regimens during 8 weeks
Reports of Suspected Pyrazinamide Side Effects
Acute Hepatic Failure (34),
Hepatic Encephalopathy (13),
Paradoxical Drug Reaction (11),
Drug Rash With Eosinophilia and Systemic Symptoms (10),
Peritoneal Tuberculosis (9),
Hepatic Function Abnormal (8),
Hepatotoxicity (8), more >>