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[Pharmacology](https://durgical.com/en/pharmacology/) · [Antituberculosis drugs](https://durgical.com/en/pharmacology/classes/antituberculosis-drugs/)

# Isoniazid

A first-line tuberculosis drug that blocks the bacillus's cell wall. Its key risks are hepatitis and peripheral neuropathy (prevented with vitamin B6).

Updated 2026-11-01

- Class: [Antituberculosis drugs](https://durgical.com/en/pharmacology/classes/antituberculosis-drugs/)
- Enzyme: Enoyl-ACP reductase InhA (M. tuberculosis)
- ATC code: J04AC01
- WHO Model List of Essential Medicines

Also called: INH, H

✂**Enoyl-ACP reductase InhA (M. tuberculosis)**Isoniazid

ⓘ The figure shows the isoniazid–NAD adduct (the active form made after KatG activates the drug) bound in InhA of M. tuberculosis.

**Target in 3D:** Enoyl-ACP reductase InhA (M. tuberculosis). PDB structure 2IDZ (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/2IDZ) · Drag to rotate · pinch to zoom

## Mechanism of action

Isoniazid is a prodrug. Inside the bacillus the catalase-peroxidase KatG converts it into a reactive radical that joins NAD; this adduct blocks InhA, an enzyme needed to make mycolic acids, the long fatty acids of the mycobacterial wall. It kills actively dividing bacilli quickly. Resistance comes mainly from mutations in katG or in inhA and its promoter.

- KatG activates isoniazid inside the bacillus
- The active form binds NAD and blocks InhA
- Mycolic acid synthesis stops and the wall fails

## Pharmacokinetics

**Absorption**
Well absorbed by mouth; food reduces absorption

**Distribution**
Into all body fluids and tissues; crosses the placenta and reaches breast milk

**Metabolism**
Liver acetylation by NAT2; slow acetylators reach higher levels and more toxicity

**Elimination**
Urine, mostly as metabolites

## Indications

- Tuberculosis, always in combination [Tuberculosis →](https://durgical.com/en/conditions/tuberculosis/)
- Pulmonary tuberculosis (HRZE intensive phase, HR continuation) [Pulmonary tuberculosis →](https://durgical.com/en/conditions/pulmonary-tuberculosis/)
- Spinal tuberculosis (Pott disease), within the combined regimen [Spinal tuberculosis (Pott disease) →](https://durgical.com/en/conditions/spinal-tuberculosis/)
- TB infection: preventive treatment alone or with rifapentine

## Adverse effects

### Common

- Peripheral neuropathy (tingling of hands and feet)
- Asymptomatic rise in liver enzymes
- Nausea and epigastric discomfort
- Rash, fever

### Serious (rare, important)

- Severe, sometimes fatal hepatitis; risk rises with age, daily alcohol use and chronic liver disease
- Seizures, psychosis and toxic encephalopathy
- Drug-induced lupus
- Overdose: refractory seizures, metabolic acidosis and coma (antidote: pyridoxine)

## Contraindications

- Previous isoniazid-associated hepatic injury
- Acute liver disease of any cause
- Previous severe reactions to isoniazid (drug fever, chills, arthritis)

## Key interactions

**Phenytoin, carbamazepine**
Isoniazid raises their levels: levels and toxicity are watched

**Paracetamol (acetaminophen)**
More toxic liver metabolites have been reported

**Alcohol**
Daily use raises the risk of hepatitis

**Tyramine- or histamine-rich foods (aged cheese, some fish)**
The label advises avoiding them during treatment because of reactions to these foods

## What is monitored

- Symptoms of hepatitis at every visit
- Liver enzymes at baseline and during treatment in people at risk
- Numbness or tingling in hands and feet
- Levels of interacting anticonvulsants

## Administration and safety

- By mouth on an empty stomach; food lowers absorption
- Usually given with pyridoxine in people at risk of neuropathy
- Directly observed treatment helps adherence
- Isoniazid also comes in fixed-dose combinations with rifampicin, pyrazinamide and ethambutol

## Nursing care

- Teach the warning signs of hepatitis: loss of appetite, nausea, dark urine, jaundice; report them at once
- Ask about tingling or burning in the feet
- Advise avoiding alcohol during treatment
- Check that pyridoxine is given to people at risk of neuropathy: malnutrition, alcohol use, diabetes
- Support adherence: stopping early breeds resistance

## Pregnancy and breastfeeding

Treatment of active tuberculosis in pregnancy is considered justified; isoniazid crosses the placenta, and preventive treatment is usually started after delivery.

## Memory aid

Isoniazid travels with two bodyguards: vitamin B6 for the nerves and liver checks for the hepatitis.

## Test yourself

Think of the answer, then tap the question to see it.

## Which bacterial enzyme activates isoniazid?

KatG, the catalase-peroxidase of M. tuberculosis; katG mutations cause high-level resistance.

## Why is pyridoxine given with isoniazid?

Isoniazid depletes vitamin B6 and causes peripheral neuropathy; pyridoxine prevents it in people at risk.

## What makes isoniazid hepatitis more likely?

Older age, daily alcohol use, chronic liver disease and injection drug use.

## What is the antidote for isoniazid overdose with seizures?

Intravenous pyridoxine (vitamin B6), with benzodiazepines.

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## Related drugs

- [Rifampicin](https://durgical.com/en/pharmacology/rifampicin/)
- [Pyrazinamide](https://durgical.com/en/pharmacology/pyrazinamide/)
- [Ethambutol](https://durgical.com/en/pharmacology/ethambutol/)
- [Ethionamide](https://durgical.com/en/pharmacology/ethionamide/)

## 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 - ISONIAZID tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9499f1cf-2f46-4047-8b71-90aee7dee854) (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=J04AC01) (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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