Drug Detail

Ethionamide

Last Updated June 10, 2016

Trade Names

Ethatyl

Drug Classification

Antimycobacterial agent, synthetic thiocarbamide derivative of isonicotinic acid

Formulations

250 mg tablets

Indications and Pharmacology

Indication: used in treatment of multidrug-resistant tuberculosis in combination with other second-line drugs.

Mechanism of action: not precisely defined, appears to inhibit peptide synthesis; may be bacteriostatic or bactericidal depending on concentration.

Pharmacokinetics: Rapidly absorbed and widely distributed in the body; metabolized in liver to active and inactive metabolites; half-life 3 hours. Good penetration of blood–brain barrier.*

Dosage

Adult Dose: 15-20 mg/kg once daily, maximum 1 g/day; dose may be divided or reduced to improve gastrointestinal tolerance. Should be taken with food to increase gastrointestinal tolerance.*

Use in Renal or Hepatic Insufficiency:

  • Creatinine clearance < 30 mL/min or if patient on haemodialysis: 250-500 mg/day.*
  • Contraindicated in patients with severe hepatic impairment.

Use in Pregnancy and Breastfeeding: Pregnancy category C. Teratogenicity in animals has been reported. Avoid use in pregnancy.*

Use in Children:

  • ≥ 10 yrs of age: adult dose.
  • < 10 yrs of age: 10 mg/kg/day increased over 1 week to 15-20 mg/kg/day (in 2 doses until well tolerated), maximum 1 g/day.

Tuberculosis meningitis in children: 20 mg/kg daily.*

Warnings

Contraindicated in patients with severe hepatic impairment, porphyria, and those hypersensitive to the drug.

Concomitant administration of pyridoxine may prevent or reduce neurotoxicity.

Use alone or failure to complete full treatment regimen may result in rapid development of resistance.

Diabetes may be difficult to control after starting this drug.

Ophthalmologic, thyroid function, and laboratory exams (serum transaminases, blood glucose) should be considered before and during therapy.*

Dose may be divided or reduced, or timing of dosage changed to improve gastrointestinal tolerance.

Caution should be used in patients with depression, psychiatric illness, chronic alcoholism, epilepsy, hypothyroidism, and diabetes.

Use alone or failure to complete full treatment regimen may result in rapid development of resistance.

Vitamin B6 (pyridoxine) 150 mg can minimise or prevent peripheral neuropathy.

Pellagra-type encephalopathy responds to niacin treatment.

Assess monthly for signs of hypothyroidism, measure thyroid stimulating hormone every 6 months in adults and every 2 months in children.*

Ethionamide has good penetration of blood–brain barrier, so consider using for miliary tuberculosis or tuberculosis meningitis.*

Drug–Drug Interactions

Increased concentration of concomitant medication: isoniazid.

Potentiation of adverse effects of concomitant medication: cycloserineterizidone (convulsions and other central nervous system toxicity); pyrazinamide (hepatotoxicity and hyperuricemia)*; ethambutol.*

Considerations for Special Populations

Drug malabsorption may occur with concomitant HIV.

Diabetes may be difficult to control.

See above for pregnancy and lactation.

Adverse Effects

Gastrointestinal intolerance (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, diarrhoea, weight loss); central nervous system effects (seizures, pellagra-like encephalopathy, acute psychosis, anxiety and depression, optic neuritis, peripheral neuropathy); hepatotoxicity; hypothyroidism, especially in HIV patients or if used with para-aminosalicylic acid.

Gynaecomastia, impotence, amenorrhoea, hypoglycaemia, hypersensitivity, alopecia, photosensitivity, arthralgia may also occur in rare instances.

*Information from Aurum Institute Drugs on the Go.
Information from US Prescribing Information.