MDR-TB Drug Comparison Tool
Select a drug to compare its properties with Ethionamide:
TL;DR
- Ethionamide (Trecator SC) is a second‑line oral TB drug that blocks mycolic‑acid synthesis.
- It’s cheaper than newer agents but carries higher risk of gastrointestinal upset and hepatotoxicity.
- Newer alternatives-Bedaquiline, Delamanid, Fluoroquinolones-offer better cure rates for MDR‑TB but are pricier.
- Choosing the right drug hinges on resistance patterns, patient comorbidities, and affordability.
- Regular drug‑susceptibility testing (DST) and monitoring are essential no matter which regimen you pick.
When clinicians face multi‑drug‑resistant tuberculosis (MDR‑TB), the drug arsenal feels like a toolbox with some worn‑out hammers and a few high‑tech power tools. Trecator SC is a tablet formulation of Ethionamide-an oral second‑line anti‑TB medication that inhibits mycolic‑acid synthesis in Mycobacterium tuberculosis. It’s been a backbone of WHO‑recommended MDR‑TB regimens for decades, but newer drugs are challenging its dominance. This article unpacks how Ethionamide stacks up against the most commonly used alternatives, so you can decide when to keep the old hammer and when to reach for a power drill.
Where Ethionamide Fits in the WHO MDR‑TB Regimen
The World Health Organization (WHO) groups anti‑TB medicines into five categories. Ethionamide belongs to Group3, the oral core drugs used when Rifampicin and Isoniazid cannot be used.
Typical WHO‑recommended adult dosing is 15‑20mg/kg daily, divided into two doses. For a 70kg adult, that means about 1g per day. Treatment lasts 18-24months, often combined with a fluoroquinolone, an injectable (like amikacin), and another Group3 drug (e.g., Cycloserine).
Key Attributes of Ethionamide
- Mechanism: Inhibits the enzyme InhA, blocking mycolic‑acid production.
- Typical dose: 15-20mg/kg per day (max 1g).
- Common side effects: Nausea, vomiting, loss of appetite, hepatotoxicity, peripheral neuropathy.
- Cost: Low‑to‑moderate; generic tablets are widely available in low‑income settings.
- Resistance profile: Often cross‑resistant with other InhA inhibitors (e.g., Isoniazid). DST is essential.
Major Alternatives to Ethionamide
Below are the six alternatives that frequently appear in modern MDR‑TB regimens.
Bedaquiline is a diarylquinoline that targets the ATP synthase of Mycobacterium tuberculosis. It’s classified as a Group5 drug (new, repurposed agents) and is taken for six months (400mg daily for two weeks, then 200mg three times weekly). Delamanid blocks mycolic‑acid synthesis via a different pathway (the methoxy‑mycolic‑acid synthase). Also a Group5 agent, the usual adult dose is 100mg twice daily for 6-24months. Fluoroquinolones (e.g., Levofloxacin, Moxifloxacin) inhibit DNA gyrase. They sit in WHO Group3 and are often the core oral drug in MDR‑TB regimens. Doses range from 500mg to 800mg daily, depending on the specific agent. Cycloserine interferes with cell‑wall peptidoglycan synthesis. It’s a Group3 oral drug, dosed at 10‑15mg/kg twice daily. Neuropsychiatric side effects are a concern. Para‑aminosalicylic acid (PAS) is a folate pathway antagonist, also in Group3. Adult dosing is 75‑100mg/kg per day in divided doses; gastrointestinal intolerance is common. Drug susceptibility testing (DST) determines which drugs a TB strain can resist. Molecular tests (e.g., Xpert MTB/RIF) and phenotypic culture guide the selection of Ethionamide versus newer alternatives.
Side‑by‑Side Comparison
| Drug | WHO Group | Mechanism | Typical Adult Dose | Key Side Effects | Cost (USD per 30days) |
|---|---|---|---|---|---|
| Ethionamide (Trecator SC) | Group3 | InhA inhibition → blocked mycolic‑acid synthesis | 15‑20mg/kg/day (max 1g) | Nausea, hepatotoxicity, peripheral neuropathy | ≈30 |
| Bedaquiline | Group5 | ATP synthase inhibition | 400mgdaily×2weeks, then 200mgTIW | QT prolongation, hepatotoxicity | ≈1,200 |
| Delamanid | Group5 | Mycolic‑acid synthesis blocker | 100mgBID | QT prolongation, nausea | ≈1,000 |
| Levofloxacin | Group3 | DNA gyrase inhibition | 750mgQD | Tendonitis, QT prolongation | ≈45 |
| Cycloserine | Group3 | Cell‑wall synthesis inhibition | 10‑15mg/kgBID | Depression, seizures | ≈70 |
| PAS | Group3 | Folate pathway antagonist | 75‑100mg/kgQD | Gastro‑intestinal upset, hyperuricemia | ≈55 |
Decision Criteria - When to Choose Ethionamide
Even with flashier options, Ethionamide remains a solid pick under certain conditions:
- Confirmed susceptibility: DST shows the isolate is sensitive to Ethionamide.
- Budget constraints: In low‑resource programs, the drug’s low price enables broader coverage.
- Limited QT‑risk: Patients with existing cardiac issues benefit from avoiding Bedaquiline or Delamanid.
- Pregnancy considerations: While data are limited, Ethionamide is categorized as Pregnancy CategoryC, whereas some newer agents lack robust safety data.
If any of these points miss the mark, a newer oral agent may give a higher chance of sputum conversion.
Practical Considerations for Clinicians
Monitoring: Baseline liver function tests (ALT/AST) before starting Ethionamide; repeat every two weeks for the first two months. Watch for peripheral neuropathy-vitamin B6 supplementation (pyridoxine 25mg daily) can mitigate.
Drug-drug interactions: Ethionamide induces hepatic enzymes, which can lower levels of oral contraceptives and certain antiretrovirals. Adjust dosages or select alternative contraception.
Pediatric dosing: WHO recommends 20mg/kg/day divided BID for children, but careful monitoring for growth impact is essential.
Adherence challenges: The drug’s strong odor and gritty texture cause poor compliance. Directly observed therapy (DOT) and counseling improve completion rates.
Related Concepts and Next Steps
Understanding Ethionamide’s place also means grasping the broader MDR‑TB landscape. Key related topics include:
- Multi‑drug‑resistant tuberculosis (MDR‑TB): defined by resistance to at least rifampicin and isoniazid.
- WHO treatment guidelines: updated every two years, they integrate emerging drugs and resistance data.
- Drug susceptibility testing (DST): the cornerstone for personalizing regimens.
- Treatment‑shortening trials: ongoing research aims to reduce therapy duration from 18‑24months to under 12.
After reading this comparison, you might explore deeper topics such as “How to interpret molecular DST results” or “Managing adverse events in MDR‑TB therapy.” Those would be natural follow‑up reads.
Frequently Asked Questions
Is Ethionamide still effective against modern MDR‑TB strains?
Effectiveness depends on local resistance patterns. In regions where InhA‑mediated resistance is low, DST often confirms susceptibility, making Ethionamide a viable component of the regimen.
How does the safety profile of Ethionamide compare with Bedaquiline?
Ethionamide’s main concerns are gastrointestinal upset and liver toxicity, which are usually manageable with supportive care. Bedaquiline, while more potent, carries a notable risk of QT‑interval prolongation and requires cardiac monitoring.
Can Ethionamide be used during pregnancy?
Data are limited; the drug is classified as CategoryC, meaning potential risk cannot be ruled out. Clinicians often weigh the benefits against risks and may prefer safer alternatives if the fetus is at high risk.
What monitoring is required for a patient on Ethionamide?
Baseline liver function tests, visual acuity, and peripheral nerve assessment are recommended. Repeat LFTs every 2weeks for the first two months, then monthly. Add pyridoxine to prevent neuropathy.
When should a clinician switch from Ethionamide to a newer drug?
Switch is advised if DST shows resistance, if the patient develops severe hepatotoxicity, or if the regimen fails to achieve sputum conversion by 2‑3months despite adherence.
Samantha Gavrin
September 27, 2025Look, the whole pharma narrative around MDR‑TB is a smoke‑screen; they push pricey gadgets like Bedaquiline because the profit margins are obscene while the cheap workhorse Ethionamide gets sidelined, even though the data clearly show it's still viable when the strain is susceptible. The conspiratorial overlap between drug‑company lobbying and WHO guideline committees is too blatant to ignore, and anyone who claims otherwise is either willfully ignorant or complicit.