Ethionamide

Chemical structure of Ethionamide

3D space-filling model of Ethionamide

Ethionamide is a second-line antibiotic used in the treatment of tuberculosis (TB), particularly in cases of multidrug-resistant tuberculosis (MDR-TB). It is not used as monotherapy but rather in combination with other antituberculosis agents to prevent the development of resistance.

Ethionamide has been associated with transient, asymptomatic elevations in serum aminotransferase levels and, in rare cases, can cause acute hepatotoxicity. Liver injury, although uncommon, can be severe.

Mechanism of Action

Ethionamide (pronounced eth-eye-on'-uh-mide) is classified as a thio-isonicotinamide compound and is structurally related to isoniazid. Like isoniazid, ethionamide is a prodrug—it must undergo activation within the mycobacterial cell to become pharmacologically active.

• The activated form of ethionamide inhibits the enzyme enoyl-acyl carrier protein reductase (InhA), which is essential for mycolic acid synthesis, a key component of the mycobacterial cell wall.
• Despite structural similarity to isoniazid, ethionamide is activated by different mycobacterial enzymes, resulting in minimal cross-resistance between the two drugs.
• Because of this, ethionamide and isoniazid can be used together in combination regimens for MDR-TB.

Indications

Ethionamide is used in:

• Multidrug-resistant tuberculosis (MDR-TB): Typically administered in combination with agents such as isoniazid, rifampin, ethambutol, and pyrazinamide
• Cases where first-line agents are contraindicated or ineffective
• Lepromatous leprosy: As an adjunctive treatment due to its antimycobacterial properties

Dosage and Administration

Ethionamide is available in 250 mg oral tablets, marketed under various generic names and the brand name Trecator.

• Initial dose: 250 mg twice daily
• Maintenance dose: Gradually increased to 15–20 mg/kg/day, divided into two or three doses
• Maximum daily dose: 1 gram
• Adjunctive therapy: Pyridoxine (Vitamin B6, 50 mg/day) is often co-administered to reduce the risk of neurotoxicity

Adverse Effects

Common side effects include:

• Gastrointestinal upset
• Nausea, diarrhea, anorexia
• Metallic taste, stomatitis
• Depression, drowsiness, and fatigue

Less common but serious side effects:

• Hepatotoxicity
• Peripheral neuropathy (more likely without pyridoxine supplementation)
• Hypothyroidism (especially in patients with co-administration of PAS)

Pharmacology

• Absorption: Well absorbed orally
• Metabolism: Primarily hepatic
• Elimination: Metabolites excreted via urine
• Half-life: Approximately 2–3 hours

Precautions and Monitoring

• Liver function tests (LFTs) should be monitored regularly during treatment
• Neurological monitoring is important due to risk of neurotoxicity
• Caution in patients with hepatic impairment or history of mental illness

Availability

Ethionamide is listed by the World Health Organization as an essential medicine for the treatment of tuberculosis. It is distributed globally through national TB programs and specialized infectious disease centers.

See Also

• Tuberculosis
• Multidrug-resistant tuberculosis
• Isoniazid
• Rifampin
• Leprosy
• Antituberculosis drugs
• Mycolic acid

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