Ethionamide Chemical formula
Synonyms: Ethionamid; Éthionamide; Ethionamidum; 2-Ethylthioisonicotinamide; Etionamid; Etionamida; Etionamidas; Etionamide; Etionamidi; 1314-TH. 2-Ethylpyridine-4-carbothioamide.
Cyrillic synonym: Этионамид.

💊 Chemical information

Chemical formula: C8H10N2S = 166.2.
CAS — 536-33-4.
ATC — J04AD03.
ATC Vet — QJ04AD03.


In Eur., Int., Jpn, and US.

Ph. Eur. 6.2

( Ethionamide). Small yellow crystals or a yellow crystalline powder. Practically insoluble in water; sparingly soluble in alcohol; soluble in methyl alcohol.

USP 31

( Ethionamide). A bright yellow powder having a faint to moderate sulfide-like odour. Slightly soluble in water, in chloroform, and in ether; sparingly soluble in alcohol and in propylene glycol; soluble in methyl alcohol. pH of a 1% slurry in water is between 6.0 and 7.0. Store in airtight containers.

💊 Adverse Effects and Treatment

Many patients cannot tolerate therapeutic doses of ethionamide and have to stop treatment. The most common adverse effects are dose-related gastrointestinal disturbances, including nausea, vomiting, diarrhoea, anorexia, excessive salivation, a metallic taste, stomatitis, and abdominal pain. Tolerance may be improved by reducing the dose, adjusting the timing of dosage, or giving an antiemetic. Mental disturbances including depression, anxiety, and psychosis have been provoked. Dizziness, drowsiness, headache, postural hypotension, and asthenia may also occur occasionally. Peripheral and optic neuropathy, diplopia and blurred vision, and a pellagra-like syndrome have occurred. Pyridoxine or nicotinamide have been suggested for the treatment or prevention of neurotoxic effects. Hepatitis may occur occasionally, with or without jaundice. The incidence of hepatotoxicity is increased when ethionamide is given with rifampicin. Other adverse effects reported include hypersensitivity reactions, thrombocytopenia and purpura, alopecia, dermatitis (including photodermatitis), endocrine disturbances, hypoglycaemia, and hypothyroidism with or without goitre. Teratogenic effects have been reported in animals.

Effects on the liver.

Use of ethionamide or protionamide with rifampicin for the treatment of multibacillary leprosy has been associated with a high incidence of hepatotoxicity. A hepatitis incidence of 4.5 to 5% has been reported for patients on ethionamide or protionamide, rifampicin, and either dapsone or clofazimine.1,2 In these studies, diagnosis of hepatitis was based on clinical assessment. When laboratory monitoring was used, an incidence of 13% was reported with a regimen of ethionamide or protionamide with rifampicin and dapsone.3 A regimen of protionamide, dapsone, rifampicin, and clofazimine has been associated with a 22% incidence based on laboratory monitoring.4Use of ethionamide with pyrazinamide has also resulted in a high incidence of abnormal liver function tests.5 In the above studies rifampicin was given daily during part or all of the regimens. The incidence of hepatotoxicity when ethionamide or protionamide is used with once-monthly rifampicin may be lower; hepatotoxicity was not reported in patients receiving monthly rifampicin and daily protionamide, isoniazid, and dapsone.6
1. Pattyn SR, et al. Hepatotoxicity of the combination of rifampinethionamide in the treatment of multibacillary leprosy. Int J Lepr 1984; 52: 1–6
2. Pattyn SR, et al. Combined regimens of one year duration in the treatment of multibacillary leprosy—II: combined regimens with rifampicin administered during 6 months. Lepr Rev 1989; 60: 118–23
3. Cartel J-L, et al. Hepatitis in leprosy patients treated by a daily combination of dapsone, rifampin, and a thioamide. Int J Lepr 1983; 51: 461–5
4. Ji B, et al. Hepatotoxicity of combined therapy with rifampicin and daily prothionamide for leprosy. Lepr Rev 1984; 55: 283–9
5. Schless JM, et al. The use of ethionamide in combined drug regimens in the re-treatment of isoniazid-resistant pulmonary tuberculosis. Am Rev Respir Dis 1965; 91: 728–37
6. Ellard GA, et al. Long-term prothionamide compliance: a study carried out in India using a combined formulation containing prothionamide, dapsone and isoniazid. Lepr Rev 1988; 59: 163–75.

💊 Precautions

Ethionamide should not be used in severe hepatic impairment. Liver function tests should be carried out before, and regularly during, treatment with ethionamide. Caution is necessary in patients with depression or other psychiatric illness. Difficulty may be experienced in the management of diabetes mellitus. Periodic monitoring of blood glucose, thyroid function, and visual function is desirable. Ethionamide is teratogenic in animals.


Ethionamide is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals or in-vitro systems.

💊 Interactions

The adverse effects of other antimycobacterials may be increased when ethionamide is used.


A psychotic reaction has been reported in a patient receiving ethionamide after excessive intake of alcohol.1
1. Lansdown FS, et al. Psychotoxic reaction during ethionamide therapy. Am Rev Respir Dis 1967; 95: 1053–5.

💊 Antimicrobial Action

Ethionamide is active only against mycobacteria including Mycobacterium tuberculosis, M. kansasii, M. leprae, and some strains of M. avium complex. Resistance develops rapidly if used alone and there is complete cross-resistance between ethionamide and protionamide. Crossresistance has been reported in vitro with isoniazid or with thioacetazone.

💊 Pharmacokinetics

Ethionamide has been given as a sugar-coated tablet or more recently as a more stable film-coated tablet. Both formulations are readily absorbed from the gastrointestinal tract: after an oral dose of 250 mg, sugar-coated tablets produce a peak plasma concentration of about 1.5 micrograms/mL after 1.5 hours, while filmcoated tablets give a peak plasma concentration of 2.16 micrograms/mL after about 1 hour. Distribution of ethionamide from the film-coated tablet into body tissues and fluids has not been studied, but is expected to be similar to that of the sugarcoated tablets. Ethionamide from sugar-coated tablets is widely distributed throughout body tissues and fluids. It crosses the placenta and penetrates the uninflamed meninges, appearing in the CSF in concentrations equivalent to those in serum. It is about 30% bound to plasma proteins. The half-life for the sugar-coated tablet is reported to be 2 to 3 hours and 1.92 hours for the filmcoated tablet. Ethionamide is extensively metabolised, probably in the liver, to the active sulfoxide and other inactive metabolites and less than 1% of a dose appears in the urine as unchanged drug.


After single oral doses of ethionamide 15 or 20 mg/kg in children with tuberculous meningitis, the peak spinal fluid concentration was reached in 1 ⁄ to 2 ⁄ hours.1 A wide range of concentrations was reported but doses of 20 mg/kg were more likely to produce spinal fluid concentrations above 2.5 micrograms/mL, the concentration considered by the authors to be essential for therapeutic success.
1. Donald PR, Seifart HI. Cerebrospinal fluid concentrations of ethionamide in children with tuberculous meningitis. J Pediatr 1989; 115: 483–6.

💊 Uses and Administration

Ethionamide is a thioamide derivative considered to be interchangeable with protionamide. It is used with other antituberculous drugs for the treatment of tuberculosis when resistance to primary drugs has developed. It has also been used, as a substitute for clofazimine, in regimens for the treatment of leprosy but less toxic alternatives are now preferred. In the treatment of resistant tuberculosis, adults may be given 15 to 20 mg/kg daily (maximum 1 g daily) orally. Ethionamide may be given in divided doses with meals, or as a single daily dose after the evening meal, or at bedtime, to minimise gastrointestinal adverse effects. For details of doses in infants, children, and adolescents, see below. Similar doses were used for the treatment of leprosy. Ethionamide has also been used as rectal suppositories; the hydrochloride has been given intravenously.

Administration in children.

For the treatment of drug-resistant tuberculosis in infants, children, and adolescents the American Academy of Pediatrics suggests an oral dose of ethionamide 15 to 20 mg/kg (to a maximum of 1 g) daily, given in 2 to 3 divided doses.

💊 Preparations

USP 31: Ethionamide Tablets.

Proprietary Preparations

Gr.: Trecator; India: Ethide; Myobid; S.Afr.: Ethatyl; Thai.: Eton; Tu rk .: Etyomid; USA: Trecator.
Published February 07, 2019.