Trecator SC (Ethionamide)

Uses

Tuberculosis

Active Tuberculosis

Trecator (ethionamide) is used with other anti-tuberculosis drugs for the treatment of active tuberculosis, primarily when Mycobacterium tuberculosis is resistant to isoniazid or rifampin, or when these drugs cannot be used due to intolerance. Ethionamide should not be used alone because resistance can develop rapidly.

Standard regimens for drug-susceptible pulmonary tuberculosis are typically at least 6 months (about 26 weeks). Treatment for drug-resistant tuberculosis is individualized and often longer; 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 accompanied by other active drugs based on susceptibility testing.

Other Mycobacterial Infections

Ethionamide has been used off-label as part of salvage regimens for certain nontuberculous mycobacterial infections. Such use should be undertaken only under the guidance of clinicians experienced in treating these infections.

Administration

Ethionamide is administered orally.

Ethionamide tablets may be taken with or without food. If gastrointestinal intolerance occurs, taking the dose with food or at bedtime and/or dividing the daily dose may improve tolerability.

Dosage

Active Tuberculosis

In the treatment of active tuberculosis, ethionamide should not be given alone. The usual adult dosage for use in conjunction with other anti-tuberculosis agents is 15–20 mg/kg/day (maximum 1 g (1,000 mg) daily). The dose may be administered once daily or, if GI intolerance occurs, in divided doses.

Initiation of therapy with 250 mg daily with gradual titration to the optimal dosage as tolerated may be beneficial. A regimen consisting of ethionamide 250 mg daily for 1–2 days, followed by 250 mg twice daily for 1–2 days with a subsequent increase to 1 g (1,000 mg) daily in 3 or 4 divided doses, has been reported.

Pediatric Dosage

Due to limited data, ethionamide generally should not be used in children younger than 12 years except when the organisms are definitely resistant to primary therapy and systemic dissemination or other life-threatening complications of tuberculosis are judged to be 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 disturbances are the most frequent adverse effects of ethionamide and may be dose related. Adverse GI effects include nausea, vomiting, diarrhea, abdominal pain, excessive salivation, metallic taste, stomatitis, anorexia, and weight loss. Adverse GI effects may be minimized by decreasing the dosage, changing the time of administration, dividing the daily dose, or using antiemetic therapy if appropriate.

Nervous System and Special Senses Effects

Psychiatric and neurologic effects (e.g., mental 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 concurrently.

Hepatic Effects

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

Severe Skin Reactions

Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP) have been reported with anti-tuberculosis drug combinations that included ethionamide. If symptoms or signs of severe skin reactions occur, discontinue suspect drug(s) immediately 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.

Serum transaminases (AST/ALT) should be determined prior to initiation and monitored monthly during therapy. If transaminases become elevated, ethionamide and companion anti-tuberculosis drug(s) may be discontinued temporarily until abnormalities resolve, then reintroduced sequentially to identify the causative agent(s).

Ophthalmologic examinations (including ophthalmoscopy) should be performed prior to and periodically during therapy. Patients should be advised to consult their clinician if blurred vision or any loss of vision, with or without ocular pain, occurs.

Blood glucose determinations should be performed prior to and periodically during therapy; diabetic patients should be alert for episodes of hypoglycemia. Periodic monitoring of thyroid function tests is recommended as hypothyroidism, with or without goiter, has been reported.

Pregnancy and Lactation

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 no information is available on excretion of ethionamide in human milk, ethionamide should be administered to nursing mothers only if the benefits outweigh the risks. Breastfed infants should be monitored for adverse effects.

Drug Interactions

Antituberculosis Agents

Ethionamide has been reported to temporarily raise serum concentrations of isoniazid. Ethionamide may potentiate adverse effects of other anti-tuberculosis drugs administered concomitantly. Convulsions have been reported when ethionamide is administered with cycloserine; use caution when the regimen includes both drugs.

Excessive ingestion of alcoholic beverages should be avoided because a psychotic reaction has been reported.

Mechanism of Action

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

Pharmacokinetics

Absorption

Ethionamide is essentially completely absorbed following oral administration and is not subjected to any appreciable first-pass metabolism. Ethionamide tablets may be administered without regard to the timing of meals.

Distribution

Ethionamide is widely distributed into body tissues and fluids and is approximately 30% bound to plasma proteins. Significant concentrations have been reported in cerebrospinal fluid in studies with 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 as ethionamide in urine.

Storage

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