Pharmacology · Antituberculosis drugs
Pyrazinamide !
A first-line TB drug that works in acidic sites and allows treatment to last 6 months instead of 9. It raises uric acid and can harm the liver.
Updated 2026-11-01
Also called: Z, PZA
The figure shows pyrazinoic acid, the active form of pyrazinamide, bound to PanD of M. tuberculosis; other targets are also proposed.
Mechanism of action
Pyrazinamide is a prodrug and a nicotinamide analogue. The bacterial enzyme pyrazinamidase (gene pncA) turns it into pyrazinoic acid, which is active only at acidic pH: inside macrophages and in necrotic lesions. Pyrazinoic acid binds PanD, needed for coenzyme A synthesis, and other targets have been proposed. It adds sterilising power to the regimen. Most resistance comes from pncA mutations.
- Pyrazinamidase (pncA) turns it into pyrazinoic acid
- Pyrazinoic acid acts in acidic sites
- It hits PanD and coenzyme A synthesis
Pharmacokinetics
- Absorption
- Well absorbed by mouth
- Distribution
- Wide, including liver, lung and cerebrospinal fluid
- Metabolism
- Liver hydrolysis to pyrazinoic acid
- Elimination
- Urine, by glomerular filtration
- Half-life
- About 9 to 10 hours, longer in kidney or liver failure
Indications
- Tuberculosis: intensive phase of the regimen Tuberculosis →
- Pulmonary tuberculosis Pulmonary tuberculosis →
- Spinal tuberculosis (Pott disease) Spinal tuberculosis (Pott disease) →
- Some regimens for drug-resistant tuberculosis
Adverse effects
Common
- Raised uric acid (usually without symptoms)
- Joint and muscle pain
- Nausea, vomiting, loss of appetite
- Rash, itching, photosensitivity
Contraindications
- Severe liver damage
- Acute gout
- Previous hypersensitivity to pyrazinamide
Key interactions
- Urine ketone test strips
- It can colour the strip and give a false reading
- Alcohol or pre-existing liver disease
- Higher risk of drug-induced hepatitis: closer follow-up
What is monitored
- Liver enzymes and uric acid at baseline and periodically
- Joint pain or swelling
- Glucose control in diabetes
Administration and safety
- By mouth, usually in fixed-dose combinations during the intensive phase
- It is stopped for good after hepatocellular damage or gouty arthritis
Nursing care
- Ask about joint pain, especially in the big toe
- Teach to report fever, loss of appetite, nausea, dark urine or jaundice
- Advise sun protection
- In diabetes, watch glucose more closely
Pregnancy and breastfeeding
The US label notes that no animal reproduction studies exist and advises use only if clearly needed.
Test yourself
Think of the answer, then tap the question to see it.
Why does pyrazinamide only work in certain places?
Its active form, pyrazinoic acid, works only at acidic pH: inside macrophages and in necrotic lesions.
Which lab value typically rises with pyrazinamide?
Uric acid, because it reduces renal urate excretion; it can trigger gout.
What does pyrazinamide add to the regimen?
Sterilising activity that lets drug-susceptible TB treatment be shortened from 9 to 6 months.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - PYRAZINAMIDE tablet (DailyMed (U.S. National Library of Medicine), 2024); WHO consolidated guidelines on tuberculosis: module 4: treatment and care (World Health Organization (WHO), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 65 (McGraw Hill, 2023).
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Representative model, for educational purposes only.