Drug information of Ethionamide

Ethionamide


Ethionamide is a second line drug in the therapy of tuberculosis used only in combination with other agents and for drug-resistance tuberculosis.  Ethionamide has been linked to transient, asymptomatic elevations in serum aminotransferase levels and in uncommon instances of acute liver injury, which can be severe.

Mechanism of effect

Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Ethionamide, like prothionamide and pyrazinamide, is a nicotinic acid derivative related to isoniazid. It is thought that ethionamide undergoes intracellular modification and acts in a similar fashion to isoniazid. Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. 

Pharmacodynamic

Ethinamate is bacteriostatic against M. tuberculosis. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturable Mycobacterium tuberculosis organisms from the lungs of H37Rv infected mice. Drug resistance developed with continued ethionamide monotherapy, but did not occur when mice received ethionamide in combination with streptomycin or isoniazid.

Pharmacokinetics

Absorption: Essentially completely absorbed following oral administration and not subjected to any appreciable first pass metabolism. Bioavailability approximately 100%.

Volume of distribution: 93.5 L [healthy volunteers]

Protein binding: Approximately 30% bound to proteins.

Metabolism: Hepatic and extensive. Metabolized to the active metabolite sulfoxide, and several inactive metabolites. The sulphoxide metabolite has been demonstrated to have antimicrobial activity against Mycobacterium tuberculosis.

Route of elimination: Less than 1% of the oral dose is excreted as ethionamide in urine. Ethionamide is extensively metabolized to active and inactive metabolites.

Half-life: 2 to 3 hours

  • Indication:

Tuberculosis, Active

Dosage

Initiate dose at 250 mg/day for 1-2 days; THEN increase to 250 mg twice daily for 1-2 days with gradual increases to highest tolerated dose; 750 mg/day average dose.

Not to exceed 1000 mg/day in 3-4 divided doses

Alerts

The use of Ethionamide alone in the treatment of tuberculosis results in rapid development of resistance. Ethionamide should be administered with at least one, sometimes two, other drugs to which the organism is known to be susceptible

Patient compliance is essential to the success of the antituberculosis therapy and to prevent the emergence of drug-resistant organisms. Therefore, patients should adhere to the drug regimen for the full duration of treatment.

Ethionamide may potentiate the adverse effects of the other antituberculous drugs administered concomitantly. Ophthalmologic examinations (including ophthalmoscopy) should be performed before and periodically during therapy with Trecator.

Ethionamide may cause live bacterial vaccines (such as typhoid vaccine) to not work as well. Do not have any immunizations/vaccinations while using this medication unless your doctor tells you to.

Prescribing Ethionamide in the absence of a proven or strongly suspected bacterial infection indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Points of recommendation

Before taking ethionamide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

If this medication causes stomach upset or nausea/vomiting, take this medication with meals.

Continue to take this medication (and other TB medications) until the full prescribed amount is finished, even if symptoms disappear. Stopping the medication too early or skipping doses may allow the bacteria to continue to grow, which may result in a return of the infection and cause the infection to be more difficult to treat (resistant).

Pregnancy level

C


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