Trecator SC (Ethionamide)

Uses

Tuberculosis

Active Tuberculosis

Trecator (ethionamide) is used with other anti-tuberculosis medicines to treat active tuberculosis, mainly when Mycobacterium tuberculosis is resistant to isoniazid or rifampicin, or when those medicines cannot be used because of intolerance. In Australian clinical practice, it is generally reserved for specialist management 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). Treatment for drug-resistant tuberculosis is individualised and often longer; in Australia, patients should be managed in consultation with an expert in drug-resistant TB.

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

Other Mycobacterial Infections

Ethionamide has been used off-label as part of salvage regimens for certain non-tuberculous 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 help improve tolerability.

Dosage

Active Tuberculosis

When treating active tuberculosis, ethionamide should not be given on its own. The usual adult dosage when used with other anti-tuberculosis medicines 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 dosage may be helpful. One reported regimen is 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 treatment and systemic spread or other life-threatening complications of tuberculosis are considered imminent. Recommended paediatric 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, diarrhoea, abdominal pain, excessive salivation, metallic taste, stomatitis, loss of appetite, and weight loss. These side effects may be reduced by lowering the dosage, changing when the medicine is taken, dividing the daily dose, or using an antiemetic if appropriate.

Nervous System and Special Senses Effects

Psychiatric and neurological effects (such as depression, restlessness, drowsiness, dizziness, and headache) have been reported. Rarely, peripheral neuritis, paraesthesia, seizures, tremor, 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 medicines 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 generally reverses after the medicine is stopped.

Severe Skin Reactions

Severe skin reactions (for example, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, and 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 medicine(s) straight 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 medicine.

Serum transaminases (AST/ALT) should be checked before treatment starts and monitored monthly during treatment. If transaminase levels become raised, ethionamide and the other anti-tuberculosis medicine(s) may be stopped temporarily until the abnormalities resolve, then reintroduced one by one to identify the causative agent(s).

Eye examinations (including ophthalmoscopy) should be performed before treatment starts and periodically during treatment. Australian patients should be advised to speak with their clinician if blurred vision or any loss of vision, with or without eye pain, occurs.

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

Pregnancy and Lactation

Safe use of ethionamide during pregnancy has not been established. Animal studies suggest a risk of harm to the developing baby, and in Australia, 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 breast milk, it should be given to breastfeeding 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. Ethionamide may increase the side effects of other anti-tuberculosis medicines used at the same time. Convulsions have been reported when ethionamide is used with cycloserine; use caution when the regimen includes both medicines.

Avoid excessive alcohol intake 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. The exact mechanism of action has not been fully clarified; ethionamide appears to inhibit peptide synthesis in susceptible organisms.

Pharmacokinetics

Absorption

Ethionamide is almost completely absorbed after oral administration and is not subject to any appreciable first-pass metabolism. Ethionamide tablets may be taken regardless of mealtimes.

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 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 tightly closed container and keep the container tightly closed.