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# Ethionamide

A second-line TB drug related to isoniazid that blocks the same enzyme, InhA. It is poorly tolerated: stomach upset, liver injury and hypothyroidism.

Updated 2026-11-01

- Class: [Antituberculosis drugs](https://durgical.com/en/pharmacology/classes/antituberculosis-drugs/)
- Enzyme: Enoyl-ACP reductase InhA (M. tuberculosis)
- ATC code: J04AD03
- WHO Model List of Essential Medicines

Also called: Eto

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

ⓘ The figure shows the ethionamide–NAD adduct (its active form after EthA activation) bound in InhA of M. tuberculosis.

**Target in 3D:** Enoyl-ACP reductase InhA (M. tuberculosis). PDB structure 2H9I (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/2H9I) · Drag to rotate · pinch to zoom

## Mechanism of action

Ethionamide is a prodrug. The mycobacterial monooxygenase EthA activates it, and the active form inhibits InhA, the same enzyme of mycolic acid synthesis that isoniazid blocks. Strains that overproduce InhA can show low-level resistance to both drugs.

- EthA activates ethionamide inside the bacillus
- The active form blocks InhA
- Mycolic acid synthesis stops

## Pharmacokinetics

**Absorption**
Nearly complete by mouth

## Indications

- Multidrug- or rifampicin-resistant tuberculosis, only when bedaquiline, linezolid, clofazimine or delamanid cannot be used [Tuberculosis →](https://durgical.com/en/conditions/tuberculosis/)

## Adverse effects

### Common

- Nausea, vomiting, loss of appetite, metallic taste
- Drowsiness, low mood, dizziness, postural hypotension
- Gynaecomastia, hair loss, acne, impotence, menstrual changes

### Serious (rare, important)

- Hepatitis
- Reversible hypothyroidism
- Neurotoxicity (paresthesias, blurred vision, depression)

## Contraindications

- Hypersensitivity to ethionamide

## Key interactions

**Cycloserine**
Adds to nervous system toxicity

## What is monitored

- Liver tests at regular intervals
- Thyroid function
- Mood and neurological symptoms
- Food intake and weight

## Administration and safety

- By mouth; taking it with food or at bedtime eases stomach upset
- Pyridoxine is given with it to prevent neurological effects

## Nursing care

- Ask about nausea and appetite; intolerance is the main reason it is stopped
- Teach the signs of hepatitis
- Watch for tiredness, cold intolerance or weight gain (hypothyroidism)
- Check that pyridoxine is given

## Memory aid

Ethionamide is isoniazid's cousin with a sour stomach and a slow thyroid.

## Test yourself

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

## Which enzyme do ethionamide and isoniazid share as target?

InhA, the enoyl-ACP reductase of mycolic acid synthesis.

## Which endocrine effect of ethionamide is checked with blood tests?

Hypothyroidism, which is reversible.

## Where does ethionamide fit in current WHO guidance?

Only in longer MDR/RR-TB regimens when bedaquiline, linezolid, clofazimine or delamanid cannot be used.

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## Related drugs

- [Isoniazid](https://durgical.com/en/pharmacology/isoniazid/)
- [Cycloserine](https://durgical.com/en/pharmacology/cycloserine/)
- [Aminosalicylic acid](https://durgical.com/en/pharmacology/aminosalicylic-acid/)

## Related conditions

- [Tuberculosis](https://durgical.com/en/conditions/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: [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=J04AD03) (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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