ETHIONAMIDE

Indications

• Tuberculosis
• Drug-resistant tuberculosis

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Ethionamide's exact mechanism of action is not fully understood, but it is believed to inhibit peptide synthesis in susceptible organisms. It may act similarly to isoniazid, which inhibits the synthesis of mycolic acids by forming a covalent adduct with the NAD cofactor, leading to inhibition of the enoyl reductase enzyme InhA in Mycobacterium tuberculosis.

Pharmacodynamics

Ethionamide is primarily bacteriostatic against Mycobacterium tuberculosis. In animal studies, initial administration of oral ethionamide decreased the number of viable M. tuberculosis bacteria. However, resistance can develop with prolonged monotherapy, which highlights the importance of combination therapy with other antitubercular drugs like streptomycin or isoniazid to prevent resistance.

Pharmacokinetics

Ethionamide is well absorbed when administered orally and undergoes hepatic metabolism. The drug's pharmacokinetics can be influenced by factors such as food intake and liver function. Its elimination half-life can vary, necessitating careful monitoring of plasma levels in patients receiving the drug. The specifics of its absorption, distribution, metabolism, and excretion profiles remain to be fully defined.

Adverse effects

• Nausea
• Vomiting
• Anorexia
• Abdominal pain
• Dizziness
• Neuropsychiatric effects
• Hepatotoxicity
• Skin rash

Interactions

• Caution with other hepatotoxic drugs
• May affect the metabolism of other drugs due to liver enzyme induction

Precautions

• Monitor liver function tests regularly
• Use with caution in patients with a history of mental health disorders
• Patients should be monitored for signs of peripheral neuropathy

Pregnancy

Ethionamide is classified as a category C drug. The potential benefits must be weighed against risks.

Breast-feeding

It is recommended to avoid breastfeeding while taking ethionamide due to potential adverse effects in the infant.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Mechanism of action

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 <i>Mycobacterium tuberculosis</i>, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA. 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. The exact mechanism of action of ethionamide has not been fully elucidated, but the drug appears to inhibit peptide synthesis in susceptible organisms.

Pharmacodynamics

Ethinamate is bacteriostatic against <i>M. tuberculosis</i>. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturable <i>Mycobacterium tuberculosis</i> 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.