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
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

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 →
Pulmonary tuberculosis (HRZE intensive phase, HR continuation) Pulmonary tuberculosis →
Spinal tuberculosis (Pott disease), within the combined regimen Spinal tuberculosis (Pott disease) →
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

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.

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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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 (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.