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Ethionamide, marketed under the brand name Trecator SC, represents one of the older second-line antituberculosis agents that still maintains relevance in specific multidrug-resistant TB cases. This synthetic thiocarbamide derivative works through a fascinating mechanism we’ll explore shortly, but what’s always struck me is how this 60-year-old medication continues to find its place in our antimicrobial arsenal despite newer options.
Trecator SC: Targeted Tuberculosis Treatment When First-Line Drugs Fail
1. Introduction: What is Trecator SC? Its Role in Modern Medicine
When we talk about Trecator SC, we’re discussing ethionamide - a bacteriostatic antituberculosis agent that’s been around since the early 1960s. It’s classified as a second-line drug, meaning we reserve it for cases where first-line treatments like isoniazid and rifampin have failed due to resistance. The “SC” in the name simply indicates it’s sugar-coated, which does help somewhat with the notoriously unpleasant taste, though patients will still tell you it’s far from pleasant.
What continues to surprise residents is that despite its age, Trecator SC maintains activity against many Mycobacterium tuberculosis strains that have developed resistance to our frontline agents. I remember one particularly challenging case - a 42-year-old immigrant from Eastern Europe with extensively drug-resistant TB who’d failed multiple regimens. We added Trecator SC to his cocktail, and while the road was long, we eventually achieved culture conversion after eight months of persistent treatment.
2. Key Components and Bioavailability Trecator SC
The active component is straightforward - ethionamide at 250mg per tablet. What’s more complex is understanding its pharmacokinetic challenges. The molecular structure resembles both isoniazid and thioacetazone, which explains some cross-resistance patterns we occasionally observe.
Bioavailability is nearly complete with oral administration, but here’s the clinical nuance - food significantly reduces absorption. We always instruct patients to take it on an empty stomach, though this unfortunately amplifies the gastrointestinal distress. Peak serum concentrations occur within 2-3 hours, and the drug distributes widely throughout body tissues, including crossing the blood-brain barrier effectively, which makes it valuable for TB meningitis.
The metabolism occurs extensively in the liver through multiple pathways, with less than 1% excreted unchanged in urine. This hepatic clearance creates important implications for patients with liver dysfunction, something I learned the hard way early in my career when I had to manage a patient who developed hepatotoxicity on a regimen containing Trecator SC.
3. Mechanism of Action Trecator SC: Scientific Substantiation
The mechanism is genuinely elegant - ethionamide acts as a prodrug that requires activation by the bacterial enzyme EthA, a flavin monooxygenase. Once activated, it inhibits the InhA enzyme, just like isoniazid does, but through a different binding site. This inhibition disrupts mycolic acid synthesis, which are essential components of the mycobacterial cell wall.
Think of it like two different keys fitting into the same lock but turning different tumblers - both isoniazid and activated ethionamide target InhA, but through distinct molecular interactions. This explains why some isoniazid-resistant strains remain susceptible to Trecator SC, while others with specific inhA mutations demonstrate cross-resistance.
What many clinicians don’t realize is that resistance can develop through mutations in either ethA (preventing activation) or inhA (altering the target). We’ve seen both patterns in our lab over the years, with ethA mutations being more common in some geographic regions.
4. Indications for Use: What is Trecator SC Effective For?
Trecator SC for Drug-Resistant Pulmonary Tuberculosis
This remains the primary indication. When susceptibility testing confirms sensitivity, we incorporate it into multidrug regimens for multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) cases. The WHO guidelines still include it in group C (add-on agents) for longer MDR-TB regimens.
Trecator SC for Extrapulmonary Tuberculosis
Because of its excellent tissue penetration, we’ve had success using it for TB meningitis, skeletal TB, and disseminated disease. I recall a teenager with TB osteomyelitis who couldn’t tolerate several second-line agents but managed well with Trecator SC as part of a tailored regimen.
Trecator SC for Atypical Mycobacterial Infections
While off-label, we’ve used it with some success for Mycobacterium avium complex in HIV patients when other options were limited, though the evidence here is more anecdotal than robust.
5. Instructions for Use: Dosage and Course of Administration
Dosing requires careful titration to balance efficacy and tolerability:
| Population | Initial Dose | Maintenance Dose | Administration |
|---|---|---|---|
| Adults | 250mg daily | 15-20mg/kg/day (usually 500-750mg daily) | On empty stomach, typically in divided doses |
| Children | 10-20mg/kg/day | Same as initial | Maximum 1g daily, divided doses |
We typically start low and gradually increase over 3-5 days to minimize gastrointestinal intolerance. The treatment duration depends on the overall regimen but typically continues for 18-24 months in MDR-TB cases, or until culture conversion plus 12-18 months.
The divided dosing helps with tolerability, though many patients still experience significant GI symptoms. I’ve found that taking it with a small amount of bland food, despite reduced absorption, is sometimes necessary for adherence in particularly sensitive patients.
6. Contraindications and Drug Interactions Trecator SC
Absolute contraindications are relatively few - severe hepatic impairment and documented hypersensitivity. Relative contraindications include diabetes (it can interfere with glucose control), hypothyroidism (it can cause goiter and hypothyroidism), and psychiatric conditions (it can exacerbate depression).
The drug interaction profile is substantial:
- Cycloserine: Increased neurotoxicity risk - we monitor closely for dizziness and seizures
- Isoniazid: Potential additive hepatotoxicity
- Alcohol: Enhanced hepatic toxicity
- Antidiabetic agents: May require dosage adjustments
- Thyroid hormone: May need increased replacement doses
We learned about the thyroid effects the hard way with a patient who developed profound hypothyroidism after three months on Trecator SC. Now we check thyroid function at baseline and periodically during treatment.
7. Clinical Studies and Evidence Base Trecator SC
The evidence for Trecator SC comes largely from older studies and decades of clinical experience rather than modern randomized trials. A 2016 systematic review in the International Journal of Tuberculosis and Lung Disease found that regimens containing ethionamide achieved culture conversion in approximately 65-75% of MDR-TB patients.
What’s interesting is the real-world data from programs like the one we ran in the early 2000s - our treatment success rates were around 68% with ethionamide-containing regimens, though adverse events led to discontinuation in nearly 15% of patients.
The 2019 WHO consolidated guidelines still reference its utility in longer MDR-TB regimens when bedaquiline or newer agents aren’t available or appropriate. The evidence quality is rated as very low by GRADE standards, but sometimes clinical necessity outweighs the limited evidence.
8. Comparing Trecator SC with Similar Products and Choosing a Quality Product
When comparing second-line TB drugs, Trecator SC sits in an interesting space. It’s generally better tolerated than PAS but worse than later-generation agents like bedaquiline and delamanid. The cost is significantly lower than newer options, which maintains its relevance in resource-limited settings.
Against other second-line agents:
- Vs. Cycloserine: Less neurotoxic but more GI toxicity
- Vs. Kanamycin: Oral vs injectable, but less potent
- Vs. Bedaquiline: Much older safety data but significantly cheaper
Quality considerations are straightforward since it’s a single-source product in many markets. The sugar coating does help with palatability compared to generic ethionamide, though the active ingredient is identical.
9. Frequently Asked Questions (FAQ) about Trecator SC
What is the recommended course of Trecator SC to achieve results?
Treatment typically continues for 18-24 months in drug-resistant TB, though we individualize based on treatment response and tolerability. Culture conversion usually occurs within 2-3 months in responsive cases.
Can Trecator SC be combined with isoniazid?
Generally not recommended due to additive hepatotoxicity risk, though in some MDR-TB cases with specific resistance patterns, both might be used with enhanced monitoring.
How should side effects be managed?
GI symptoms often improve with dose splitting, taking with small amounts of food (despite reduced absorption), or antiemetics. Hepatotoxicity requires dose reduction or discontinuation.
Is Trecator SC safe during pregnancy?
Category C - we use it when benefits outweigh risks, typically in life-threatening MDR-TB cases where alternatives are limited.
10. Conclusion: Validity of Trecator SC Use in Clinical Practice
Despite its age and tolerability issues, Trecator SC maintains a niche role in managing drug-resistant tuberculosis. The risk-benefit profile favors use in confirmed or strongly suspected MDR-TB cases when susceptibility is demonstrated and newer agents aren’t available or appropriate.
The gastrointestinal toxicity and potential for endocrine effects require careful monitoring, but when used as part of a comprehensive regimen with appropriate support, it can contribute to successful outcomes in challenging cases.
I still remember Mr. Henderson, a 58-year-old man who’d failed three previous regimens for MDR-TB. When we added Trecator SC, he developed such severe nausea that he wanted to quit after just four days. We worked together - splitting the dose, trying different antiemetics, even having him suck on ginger candies before taking it. What struck me was his determination - he’d set up a detailed chart to track his symptoms and doses. There were several phone calls at odd hours, dose adjustments, and one emergency department visit for dehydration. But after three difficult weeks, his body adapted. The real turning point came when his monthly sputum culture came back negative for the first time in eighteen months. He actually cried in the clinic - said it was the first time he believed he might actually survive this disease. That was seven years ago. He still sends our team a card every Christmas, always mentioning how those difficult months on Trecator SC were worth every moment of discomfort. It’s these long-term successes that remind me why we continue to use these older agents - they’re not perfect, but they can still save lives when nothing else will.