Ethionamide (Trecator SC) vs Top TB Drug Alternatives - 2025 Guide

Oct, 26 2025

Quick Takeaways

Ethionamide is a second‑line TB drug mainly used for multidrug‑resistant cases.
Newer agents like Bedaquiline and Delamanid offer higher cure rates but cost more.
Fluoroquinolones (Moxifloxacin, Levofloxacin) are versatile alternatives with good oral bioavailability.
Side‑effect profiles differ: Ethionamide often causes gastrointestinal upset, while Linezolid can trigger bone‑marrow suppression.
Choosing an alternative depends on resistance pattern, patient comorbidities, and budget.

When doctors treat multidrug‑resistant tuberculosis (MDR‑TB), Ethionamide is one of the go‑to drugs. Sold as Trecator SC, it works by blocking the bacterial enzyme involved in mycolic‑acid synthesis. While effective, Ethionamide brings a lineup of gastrointestinal and hepatic side effects that make many clinicians ask: are there better options?

Below we compare Ethionamide with the most widely accepted alternatives on the market today. The goal isn’t to pick a “winner” but to give you a clear picture of each drug’s mechanism, typical use, side‑effect profile, drug‑interaction risk, and cost in Australia (2025). Armed with that data, patients and prescribers can decide which regimen fits their clinical and financial situation.

How Ethionamide Works and Who Uses It

Ethionamide is a thioamide that inhibits the enzyme InhA, a key step in mycolic‑acid production for Mycobacterium tuberculosis. It’s classified as a second‑line agent, meaning it’s reserved for cases where first‑line drugs (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) fail or the strain is resistant.

Typical dosing in adults is 15-20 mg/kg per day, split into two doses. Treatment usually lasts 6-24 months depending on disease severity and sputum conversion. Because it’s available only in a sustained‑release (SC) tablet, adherence can be a challenge.

Leading Alternatives at a Glance

Key attributes of Ethionamide and five major alternatives (2025 AU$ prices are approximate)
Drug	Class / Mechanism	Typical Indication	Common Side Effects	Key Drug Interactions	Cost (AU$ per month)
Ethionamide	Thioamide - InhA inhibitor	MDR‑TB, especially when resistance to fluoroquinolones exists	nausea, vomiting, hepatotoxicity, hypothyroidism	Concurrent use with antacids reduces absorption; CYP2C19 inhibitors raise levels	~120
Bedaquiline	Diarylquinoline - ATP synthase inhibitor	Extensively drug‑resistant TB (XDR‑TB) and MDR‑TB	QT prolongation, hepatic enzymes rise, arthralgia	Strong CYP3A4 inducers (e.g., Rifampicin) lower efficacy	~3,200
Delamanid	Nitro‑imidazooxazole - Mycolic‑acid synthesis blocker	MDR‑TB, used when fluoroquinolones not tolerated	QT prolongation, nausea, headache	Co‑administration with other QT‑prolonging drugs requires ECG monitoring	~2,800
Linezolid	Oxazolidinone - Protein synthesis inhibition	MDR‑TB, XDR‑TB, often as part of a rescue regimen	Peripheral neuropathy, myelosuppression, visual disturbances	MAO inhibitors - risk of serotonin syndrome; warfarin potency may increase	~850
Moxifloxacin	Fluoroquinolone - DNA gyrase inhibitor	First‑line companion in MDR‑TB regimens; also used for drug‑sensitive TB when fluoroquinolones are preferred	Tendinitis, QT prolongation, GI upset	Antacids, iron supplements reduce absorption; CYP1A2 inhibitors raise levels	~200

When a Newer Agent Makes Sense: Bedaquiline & Delamanid

Bedaquiline entered the market in 2012 and quickly became a cornerstone for XDR‑TB. Its unique ATP‑synthase inhibition means it works even against strains resistant to all classic drugs. The downside? Price. At roughly AU$3,200 per month, it’s out of reach for many patients without government subsidies. Additionally, the QT‑prolongation risk demands baseline and periodic ECGs.

Delamanid offers a similar potency but with a slightly lower price tag (AU$2,800). It’s favored when clinicians need an oral option that avoids the injectable toxicity of older agents like aminoglycosides. Like Bedaquiline, cardiac monitoring is essential, especially if combined with Moxifloxacin or other QT‑affecting drugs.

Day of the Dead altar showing Bedaquiline and Delamanid as glowing skull warriors with ECG strips and coins.

Old‑School but Reliable: Fluoroquinolones

Fluoroquinolones such as Moxifloxacin remain the workhorse for many MDR‑TB regimens. Their oral bioavailability (~90 %) allows patients to stay at home, reducing hospitalization costs. Side effects are generally manageable-mainly gastrointestinal upset and occasional tendon issues. However, resistance is rising in areas with over‑use for respiratory infections, so susceptibility testing is a must.

If a patient can’t tolerate Moxifloxacin, Levofloxacin (not in the table) is an alternative with a slightly better safety profile but a lower MIC against TB strains. Both require caution with antacids, as the high pH impairs absorption.

Targeting the Niche: Cycloserine & PAS

Cycloserine is a bacteriostatic agent that interferes with cell‑wall synthesis. It’s useful when the regimen needs an additional oral pill without overlapping toxicity. The catch is its neuropsychiatric side‑effect-patients can develop anxiety, depression, or seizures, especially if they have a prior psychiatric history.

p‑aminosalicylic acid (PAS) (often just called PAS) is another older oral drug. It’s effective but notorious for causing severe GI irritation and hyperuricemia. Because of these unpleasant effects, PAS is typically reserved for patients who have exhausted newer options.

Putting It All Together: Decision Guide

Choosing the right alternative to Ethionamide hinges on three pillars: resistance profile, patient tolerance, and budget.

Resistance profile: If a sputum culture shows fluoroquinolone susceptibility, Moxifloxacin is the logical first swap. If resistance extends to fluoroquinolones, look to Bedaquiline or Delamanid.
Patient tolerance: Patients with liver disease may struggle with Ethionamide’s hepatotoxicity. In such cases, Linezolid (monitor blood counts) or a fluoroquinolone may be safer.
Budget: For publicly funded patients under the Australian Pharmaceutical Benefits Scheme (PBS), Bedaquiline and Delamanid are subsidised but still costlier than Ethionamide or Moxifloxacin. Discuss financial assistance early.

Doctor skeleton consulting a patient skeleton, surrounded by a decision tree, money, and ECG monitor.

Practical Tips for Switching from Ethionamide

Confirm drug‑susceptibility results before making any change.
Baseline ECG: essential if the new drug can affect QT interval (Bedaquiline, Delamanid, Moxifloxacin).
Check for interactions with current meds - especially antiretrovirals in HIV‑positive patients.
Start the new agent at the recommended dose; monitor liver enzymes (ALT/AST) for the first 8 weeks.
Educate the patient about side‑effects to watch for: visual changes (Linezolid), tendon pain (fluoroquinolones), or mood swings (Cycloserine).
Schedule monthly follow‑ups for the first three months, then every two months thereafter.

Future Outlook: New Drugs on the Horizon

Research pipelines are promising. Compounds like pretomanid (a nitroimidazole) have shown high efficacy in combination with Bedaquiline and Linezolid, forming the “BPaL” regimen that may soon become a standard for XDR‑TB. While not yet widely available in Australia, clinical trials suggest cure rates above 90 % with shorter treatment durations.

Nevertheless, until those agents become mainstream, clinicians will continue to juggle existing tools-balancing efficacy, safety, and cost-to replace Ethionamide when needed.

Key Takeaways for Patients

Never stop Ethionamide without a doctor’s order; abrupt changes can worsen resistance.
If side effects become intolerable, ask about a fluoroquinolone or newer oral drugs like Bedaquiline.
Keep a medication diary - note any nausea, headaches, or mood changes and share with your healthcare team.
Ask about financial assistance programs if cost is a barrier; many newer drugs are subsidised under PBS.

What makes Ethionamide different from newer TB drugs?

Ethionamide is a second‑line thioamide that blocks mycolic‑acid synthesis. Newer drugs like Bedaquiline target ATP synthase, while fluoroquinolones inhibit DNA gyrase. These newer mechanisms often work against strains resistant to Ethionamide, but they can be pricier and may need cardiac monitoring.

When should a clinician consider switching from Ethionamide?

Switching is advised when a patient experiences severe gastrointestinal or liver toxicity, when drug‑susceptibility testing shows resistance, or when a more effective, less toxic regimen (e.g., Bedaquiline‑based) is affordable and available.

Are there any major drug interactions with Ethionamide?

Yes. Antacids containing aluminum or magnesium can lower Ethionamide absorption. CYP2C19 inhibitors (like fluvoxamine) raise its plasma levels, increasing side‑effect risk. Always review the full medication list with a pharmacist.

How do the costs of alternatives compare in Australia?

Ethionamide costs about AU$120 per month, making it the most affordable second‑line option. Moxifloxacin is around AU$200, Linezolid AU$850, while Bedaquiline and Delamanid exceed AU$2,800‑3,200 per month. PBS subsidies can offset some of the higher prices for eligible patients.

What monitoring is required when using Bedaquiline or Delamanid?

Both drugs can prolong the QT interval, so a baseline ECG is mandatory, followed by monthly ECGs for the first six months. Liver function tests should also be checked regularly, as hepatic enzymes may rise.

1 Comments

Hershel Lilly
October 26, 2025 AT 13:46

Ethionamide's role in MDR‑TB regimens is often dictated by resistance patterns rather than patient preference. The drug's bioavailability issues make adherence a real hurdle, especially with the sustained‑release formulation. In practice, clinicians balance its low cost against the gastrointestinal side‑effects that can derail therapy. Monitoring liver enzymes early on is prudent, even if the patient seems tolerable at first.