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# 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

- Class: [Antituberculosis drugs](https://durgical.com/en/pharmacology/classes/antituberculosis-drugs/)
- Enzyme: Aspartate decarboxylase PanD (M. tuberculosis), target of pyrazinoic acid
- ATC code: J04AK01
- WHO Model List of Essential Medicines

Also called: Z, PZA

✂**Aspartate decarboxylase PanD (M. tuberculosis), target of pyrazinoic acid**Pyrazinamide

ⓘ The figure shows pyrazinoic acid, the active form of pyrazinamide, bound to PanD of M. tuberculosis; other targets are also proposed.

**Target in 3D:** Aspartate decarboxylase PanD (M. tuberculosis), target of pyrazinoic acid. PDB structure 6OYY (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6OYY) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/tuberculosis/)
- Pulmonary tuberculosis [Pulmonary tuberculosis →](https://durgical.com/en/conditions/pulmonary-tuberculosis/)
- Spinal tuberculosis (Pott disease) [Spinal tuberculosis (Pott disease) →](https://durgical.com/en/conditions/spinal-tuberculosis/)
- 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

### Serious (rare, important)

- Hepatotoxicity (its main serious effect)
- Acute gout
- Rarely thrombocytopenia, sideroblastic anaemia or interstitial nephritis

## 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.

## Memory aid

Pyrazinamide's two Ps: Prefers acid pH, Pushes up uric acid.

## 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.

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## Related drugs

- [Isoniazid](https://durgical.com/en/pharmacology/isoniazid/)
- [Rifampicin](https://durgical.com/en/pharmacology/rifampicin/)
- [Ethambutol](https://durgical.com/en/pharmacology/ethambutol/)

## Related conditions

- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)
- [Pulmonary tuberculosis](https://durgical.com/en/conditions/pulmonary-tuberculosis/)
- [Spinal tuberculosis (Pott disease)](https://durgical.com/en/conditions/spinal-tuberculosis/)

[← Back to the class: Antituberculosis drugs](https://durgical.com/en/pharmacology/classes/antituberculosis-drugs/)

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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=566db230-3d73-482f-b67d-defd0b2dc46c) (DailyMed (U.S. National Library of Medicine), 2024); [WHO consolidated guidelines on tuberculosis: module 4: treatment and care](https://www.who.int/publications/i/item/9789240107243) (World Health Organization (WHO), 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J04AK01) (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.

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