Trecator SC (Ethionamide)

Uses

Tuberculosis

Active Tuberculosis

Trecator (ethionamide) is used with other anti-tuberculosis medications to treat active tuberculosis, mainly when Mycobacterium tuberculosis is resistant to isoniazid or rifampin, or when those drugs cannot be used because of intolerance. In Canada, it is generally reserved for specialist-managed treatment of drug-resistant TB. Ethionamide should not be used on its own because resistance can develop quickly.

Standard regimens for drug-susceptible pulmonary tuberculosis usually last at least 6 months (about 26 weeks). In Canada, treatment for drug-resistant tuberculosis is individualized and often longer, and patients should be managed in consultation with an expert in drug-resistant TB.

If ethionamide is added as a new drug to a regimen in patients with proven or suspected drug-resistant tuberculosis, it should be used with other active drugs based on susceptibility testing.

Other Mycobacterial Infections

Ethionamide has been used off-label as part of salvage regimens for some nontuberculous mycobacterial infections. It should only be used this way under the guidance of clinicians experienced in treating these infections.

Administration

Ethionamide is taken by mouth.

Ethionamide tablets can be taken with or without food. If stomach upset occurs, taking the dose with food or at bedtime and/or splitting the daily dose may improve tolerability.

Dosage

Active Tuberculosis

When treating active tuberculosis, ethionamide should not be given alone. The usual adult dose when used with other anti-tuberculosis agents is 15-20 mg/kg/day (maximum 1 g (1,000 mg) daily). The dose may be taken once daily or, if GI intolerance occurs, in divided doses.

Starting treatment with 250 mg daily and gradually increasing to the best-tolerated dose may be helpful. One reported regimen uses ethionamide 250 mg daily for 1-2 days, followed by 250 mg twice daily for 1-2 days, then increased to 1 g (1,000 mg) daily in 3 or 4 divided doses.

Pediatric Dosage

Because data are limited, ethionamide generally should not be used in children younger than 12 years unless the organisms are clearly resistant to first-line therapy and widespread infection or other life-threatening complications of tuberculosis are considered imminent. Recommended pediatric dosing in references ranges from 10-20 mg/kg/day (up to 1 g (1,000 mg) daily) given in 2 or 3 divided doses; once-daily dosing has also been used in some situations under specialist supervision.

Cautions

GI Effects

Gastrointestinal problems are the most common side effects of ethionamide and may be dose-related. GI side effects include nausea, vomiting, diarrhea, abdominal pain, excessive salivation, a metallic taste, stomatitis, loss of appetite, and weight loss. These effects may be reduced by lowering the dose, changing when it is taken, splitting the daily dose, or using anti-nausea treatment when appropriate.

Nervous System and Special Senses Effects

Psychiatric and neurologic effects (for example, depression, restlessness, drowsiness, dizziness, headache) have been reported. Rarely, peripheral neuritis, paresthesia, seizures, tremors, hallucinations, diplopia, optic neuritis, and blurred vision have occurred. Some clinicians use pyridoxine (vitamin B6) to help prevent or manage neuropathy, especially when other neurotoxic anti-tuberculosis drugs are used at the same time.

Hepatic Effects

Temporary increases in serum bilirubin and transaminases (AST/ALT) have been reported. Hepatitis, with or without jaundice, has also been reported. Hepatotoxicity is generally reversible after the drug is stopped.

Severe Skin Reactions

Severe skin reactions (for example, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP) have been reported with anti-tuberculosis drug combinations that included ethionamide. If symptoms or signs of a severe skin reaction occur, stop the suspected drug(s) right away and seek urgent medical care.

Precautions and Contraindications

Ethionamide is contraindicated in patients with severe hepatic impairment and in patients who are hypersensitive to the drug.

In clinical practice, serum transaminases (AST/ALT) should be checked before treatment starts and monitored monthly during therapy. If transaminases become elevated, ethionamide and the accompanying anti-tuberculosis drug(s) may be stopped temporarily until the abnormalities resolve, then restarted one at a time to identify the causative agent(s).

Eye examinations, including ophthalmoscopy, should be done before treatment and periodically during therapy. Patients should be advised to contact their clinician if blurred vision or any loss of vision, with or without eye pain, occurs.

Blood glucose should be checked before treatment and periodically during therapy; patients with diabetes should watch for episodes of hypoglycemia. Periodic monitoring of thyroid function is recommended, as hypothyroidism, with or without goiter, has been reported.

Pregnancy and Lactation

The safe use of ethionamide during pregnancy has not been established. Animal studies indicate teratogenic potential, and ethionamide should generally be avoided in women who are pregnant or likely to become pregnant unless the clinician considers it an essential part of treatment.

Because there is no information on whether ethionamide passes into human milk, it should be given to nursing mothers only if the benefits outweigh the risks. Breastfed infants should be monitored for side effects.

Drug Interactions

Antituberculosis Agents

Ethionamide has been reported to temporarily raise serum concentrations of isoniazid. It may also increase the side effects of other anti-tuberculosis drugs given at the same time. Convulsions have been reported when ethionamide is given with cycloserine; use caution when the regimen includes both drugs.

Avoid excessive alcohol use because a psychotic reaction has been reported.

Mechanism of Action

Ethionamide may be bacteriostatic or bactericidal depending on the drug concentration at the infection site and the susceptibility of the organism. Its exact mechanism of action has not been fully established; ethionamide appears to inhibit peptide synthesis in susceptible organisms.

Pharmacokinetics

Absorption

Ethionamide is essentially completely absorbed after oral administration and does not undergo any appreciable first-pass metabolism. Ethionamide tablets may be taken without regard to meals.

Distribution

Ethionamide is widely distributed in body tissues and fluids and is approximately 30% bound to plasma proteins. Significant concentrations have been reported in cerebrospinal fluid in studies using earlier formulations.

Elimination

The mean half-life reported for the film-coated tablet is approximately 1.9 hours. Less than 1% of an oral dose is excreted in the urine as ethionamide.

Storage

Store at 20-25°C (68-77°F). Dispense in a tight container and keep the container tightly closed.