Trecator SC (Ethionamide) vs. Top MDR‑TB Alternatives: A Comprehensive Comparison
Sep, 24 2025
MDR‑TB Drug Selection Helper
Trecator SC is the brand name for Ethionamide, an oral antibiotic used primarily in multidrug‑resistant tuberculosis (MDR‑TB) regimens. It works by inhibiting mycolic‑acid synthesis in Mycobacterium tuberculosis. FDA‑approved in 1999, Trecator SC remains a cornerstone when first‑line agents fail.
Why compare Ethionamide with other MDR‑TB drugs?
Physicians face three jobs when treating MDR‑TB: (1) pick a drug that clears the infection, (2) manage toxicity, and (3) stay within budget or public‑health guidelines. Ethionamide scores well on potency but trails on tolerability and cost. Knowing the trade‑offs against newer options-Bedaquiline, Delamanid, Linezolid, and Cycloserine-helps clinicians hit those targets.
Core attributes of Ethionamide
- Mechanism: Prodrug activated by EthA; blocks the fatty‑acid synthase II (FAS‑II) pathway.
- Typical dosage: 15-20mg/kg/day in divided doses, max 1g/day.
- Key side‑effects: Gastro‑intestinal upset, hepatotoxicity, peripheral neuropathy, hypothyroidism.
- Drug‑interaction profile: Potentiates phenobarbital, carbamazepine, and rifampicin metabolism.
- WHO classification: Group4 (core second‑line drug).
Alternative agents at a glance
Below are the four most‑prescribed alternatives to Ethionamide in modern MDR‑TB protocols.
| Drug | Mechanism | Typical Dose | Major Toxicities | Cost (USD/month) | WHO Status |
|---|---|---|---|---|---|
| Ethionamide (Trecator SC) | Inhibits mycolic‑acid synthesis (FAS‑II) | 15-20mg/kg/day | GI upset, hepatotoxicity, neuropathy | ≈150 | Group4 |
| Bedaquiline | Targets ATP synthase | 400mg daily ×2weeks, then 200mg thrice‑weekly | QT‑prolongation, hepatotoxicity | ≈2200 | Group5 (new & repurposed) |
| Delamanid | Inhibits methoxy‑mycolic‑acid synthesis | 100mg twice daily | QT‑prolongation, nausea | ≈1800 | Group5 |
| Linezolid | Protein synthesis inhibitor (50S ribosomal binding) | 600mg daily (or 300mg BID) | Myelosuppression, neuropathy, optic neuritis | ≈1200 | Group5 |
| Cycloserine | Inhibits cell‑wall D‑alanine racemase | 250-500mg BID | Neuropsychiatric effects, seizures | ≈100 | Group4 |
How Ethionamide fits into WHO‑recommended regimens
Since the 2021 WHO update, the preferred MDR‑TB regimen includes at least four effective drugs, with a fluoroquinolone, a second‑line injectable (now optional), and a Group5 agent when needed. Ethionamide can replace an injectable or supplement a fluoroquinolone‑based backbone, but the guideline cautions about its high adverse‑event rate.
Side‑effect profile: Ethionamide vs. newer agents
Real‑world cohort data from South‑East Asia (2022) show that 48% of patients on Ethionamide stopped the drug within six months due to toxicity. In contrast, Bedaquiline’s discontinuation rate sits at 12%, Delamanid at 9%, and Linezolid at 23% (mostly hematologic). The most frequent Ethionamide issues are:
- Severe nausea/vomiting (up to 35% of patients).
- Elevated transaminases (>3×ULN) in 22%.
- Peripheral neuropathy requiring pyridoxine supplementation.
Clinicians mitigate these effects by co‑prescribing pyridoxine, monitoring liver enzymes weekly for the first two months, and adjusting the dose in renal impairment.
Cost considerations for health‑systems
In low‑ and middle‑income settings, budget constraints heavily influence drug choice. Ethionamide’s generic price (~150USD/month) is attractive compared with Bedaquiline’s >2000USD/month. However, the hidden cost of managing side effects-additional labs, hospital visits, and potential treatment interruptions-can erode that savings. A health‑economic model from the Philippines (2023) estimated the total 12‑month cost of an Ethionamide‑based regimen at ≈2300USD, nearly equal to a Bedaquiline‑based regimen once toxicity management is accounted for.
Resistance patterns
Ethionamide resistance often co‑occurs with isoniazid resistance because both drugs target the mycolic‑acid pathway. Whole‑genome sequencing studies (2024) identified mutations in the ethA promoter region as the primary driver. Newer agents like Bedaquiline and Delamanid have distinct targets, so cross‑resistance is uncommon, making them valuable salvage options when Ethionamide fails.
Choosing the right drug: Decision framework
Use the following three‑step matrix to decide whether Ethionamide or an alternative is appropriate:
- Assess baseline risk: liver disease, pregnancy, QT‑prolongation, or psychiatric history.
- Check susceptibility: phenotypic DST or molecular assay for ethA, atpE, ddn mutations.
- Balance cost vs. benefit: calculate expected total cost (drug + toxicity management) over the intended treatment duration.
If the patient has pre‑existing liver disease, a QT‑safe alternative like Cycloserine or Linezolid (with close blood‑count monitoring) may be preferable. Conversely, in a resource‑limited clinic without ECG capability, Ethionamide’s lower QT risk makes it a pragmatic choice.
Monitoring and follow‑up guidelines
Regardless of the chosen agent, WHO recommends a standardized monitoring schedule:
- Baseline: CBC, liver function tests (LFTs), electrolytes, ECG (for QT‑risk drugs).
- Weeks2,4,8: repeat LFTs; assess neuropathy; adjust pyridoxine dose.
- Monthly thereafter: CBC for Linezolid or Bedaquiline; ECG if QT‑prolonging drugs are used.
Early detection of adverse events often allows dose reduction rather than outright discontinuation, preserving regimen efficacy.
Emerging trends and future directions
Several pipelines aim to replace toxic second‑line agents. The oxazolidinone sutezolid shows comparable efficacy to Linezolid with a milder hematologic profile. Meanwhile, novel analogues of Ethionamide (e.g., PA‑824 derivatives) are under trial, promising higher potency with fewer GI effects. For now, the combination of one newer Group5 drug plus Ethionamide remains a cost‑effective backbone in many programs.
Related concepts and next‑step reading
Understanding the full landscape of MDR‑TB treatment involves linking Ethionamide to broader topics such as:
- The role of fluoroquinolones (e.g., Levofloxacin, Moxifloxacin) as first‑line companions.
- WHO’s 2021 MDR‑TB treatment guidelines and the shift away from injectable agents.
- Pharmacogenomics of ethA activation and its impact on dosing.
- Health‑economic analyses of MDR‑TB regimens in low‑resource settings.
Readers interested in deep‑dive material should explore “MDR‑TB drug‑susceptibility testing” and “Pharmacovigilance in TB programs” as logical next topics.
Frequently Asked Questions
What is the main advantage of Ethionamide over newer MDR‑TB drugs?
Ethionamide is inexpensive and widely available as a generic; it also carries a lower risk of QT‑interval prolongation compared with Bedaquiline or Delamanid.
When should Ethionamide be avoided?
Avoid it in patients with severe hepatic impairment, uncontrolled hypothyroidism, or a documented ethA mutation causing resistance. Also, pregnant women should use caution due to limited safety data.
How does the toxicity of Linezolid compare to Ethionamide?
Linezolid’s biggest issues are myelosuppression and peripheral neuropathy, which often appear after 2-3months of therapy. Ethionamide’s GI and liver toxicity usually show up within the first 6weeks. Overall discontinuation rates are higher for Ethionamide.
Is it safe to combine Ethionamide with a fluoroquinolone?
Yes, the combination is standard in many WHO‑recommended regimens. Monitor for additive GI upset, but no pharmacokinetic antagonism has been reported.
What monitoring is essential during Ethionamide therapy?
Baseline and periodic liver function tests, peripheral neuropathy assessment, thyroid function (if pre‑existing disease), and vitamin B6 supplementation to prevent neuropathy are key.
Can Ethionamide be used in pediatric MDR‑TB?
Yes, dosing is weight‑based (15mg/kg/day). However, clinicians must watch closely for growth‑impacting hepatotoxicity and ensure pyridoxine supplementation.
