Ethionamide is a second-line anti-TB drug of the thioamide group, with bacteriostatic activity against Mycobacterium tuberculosis. It is used in MDR-TB regimens.
Also known as: Trecator
Ethionamide and isoniazid are both hepatotoxic. Coadministration increases the risk of hepatotoxicity.
Isoniazid causes hepatotoxicity via reactive metabolites (hydrazine, acetylhydrazine) that form adducts with hepatic proteins. Ethionamide causes hepatotoxicity via sulfoxide metabolites that induce oxidative stress. Although the mechanisms differ, the final result is additive hepatocellular damage. Studies demonstrated that severe hepatotoxicity incidence (ALT >5x ULN) is ~5% with isoniazid alone, but may reach 10-15% with the combination. Mandatory monitoring: ALT/AST weekly for the first 2 months, then monthly. Discontinue if ALT >5x ULN or if symptoms develop (nausea, jaundice, right hypochondrial pain).
Ethionamide + isoniazid: additive hepatotoxicity. Monitor transaminases weekly.
Both cause hepatotoxicity by different mechanisms — isoniazid via reactive metabolites (hydrazine) and ethionamide via sulfoxide metabolites. The combination potentiates liver damage.
ALT/AST, bilirubin, INR, symptoms (nausea, jaundice, right hypochondrial pain).
Severe drug-induced hepatitis, hepatic failure.
Monitor transaminases (ALT/AST) weekly for the first 2 months, then monthly. Discontinue if ALT >5x ULN or symptoms of hepatotoxicity.
EMC-UK (MHRA) — approved Ethionamide SmPC: https://www.medicines.org.uk/emc/product/6740/smpc ; DailyMed/FDA (NIH/NLM) — approved Isoniazid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6f269898-c9e5-4b73-b141-b5e8e6a4d7b3
Food improves absorption and reduces nausea. Tyramine-rich foods may cause cheese-like reaction.
Always take with food. Avoid tyramine-rich foods (cured cheese, processed meats, fermented foods).
EMC-UK (MHRA) — approved Ethionamide SmPC: https://www.medicines.org.uk/emc/product/6740/smpc
Ethionamide may inhibit MAO, causing hypertensive reaction with tyramine-rich foods.
Avoid: cured cheese, cured meats, soy sauce, beer, red wine.
EMC-UK (MHRA) — approved Ethionamide SmPC: https://www.medicines.org.uk/emc/product/6740/smpc
No documented disease interactions.
Animal studies demonstrated fetal effects. Limited human data. Use only for severe MDR-TB.
Avoid in 1st trimester. Use in 2nd/3rd trimesters only when other options are exhausted.
Unknown if excreted in breast milk. Artificial feeding is recommended.
Reliable contraception is recommended.
EMC-UK (MHRA) — approved Ethionamide SmPC: https://www.medicines.org.uk/emc/product/6740/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Ethionamide is a prodrug that requires activation by the M. tuberculosis LiuA enzyme (monooxygenase) to produce the active metabolite (ethionic sulfinic acid) that inhibits mycolic acid synthesis.
Activated by LiuA (mycobacterial monooxygenase) to the active sulfoxide, which inhibits mycolic acid synthesis (essential components of mycobacterial cell wall).
Oral bioavailability: nearly complete. Tmax: 2-3 hours. Absorption improved with food.
Hepatically metabolised (sulfoxidation). Half-life: 2-3 hours. The active metabolite half-life is longer.
2-3 hours (parent drug); active metabolite longer. Elimination: urine (metabolites).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
