Ethionamide

Ethionamide is an Antitubercular agent belonging to nicotinamide derivative

Ethionamide is used in the Treatment of Tuberculosis.

Ethionamide isReadily absorbed from the GI tract and get Widely distributed throughout body tissues and fluids. It Crosses placenta and CSF with Volume of distribution of 93.5 L. Plasma protein binding: 30%.It is Extensively metabolised in the liver to the active metabolite sulfoxide and some inactive metabolites.It get excreted Via urine (<1% as unchanged drug). Elimination half-life: Approx 2 hr.

The Tmax of Ethionamide was achieved within 1 hr.

Ethionamide shows common side effects like mental depression, anxiety, drowsiness, dizziness, restlessness, headache, peripheral neuritis, paraesthesia, seizures, etc.

Ethionamide is available in the form of Tablets.

Ethionamide is available in India, Germany, China, Italy, USA

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

Ethionamide is used in the Treatment of Tuberculosis.

Ethionamide is approved for use in the following clinical indications

• Tuberculosis: Treatment of active tuberculosis, in combination with other antituberculosis agents, in patients with Mycobacterium tuberculosis resistant to isoniazid or rifampin, or when there is intolerance to other drugs.

Ethionamide is available in various strengths as 250 mg

Ethionamide is available in the form of Tablets.

• Dosage Adjustment in Hepatic impairment Patient

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

• Dosage Adjustment for Pediatric Patients

Active tuberculosis infection (excluding meningitis), treatment (second-line therapy):

• Note: Recommendations often change due to epidemiology (resistance) and emerging information; consult CDC and WHO for detailed information. Always use as part of a multidrug regimen. Coadministration of pyridoxine is recommended for prevention of neurotoxic effects.

• Infants, Children, and Adolescents: Oral: 15 to 20 mg/kg/day in divided doses once or twice daily (in HIV-exposed/-infected, divided doses three times daily have also been recommended); usual adult dose range: 250 to 500 mg/dose; maximum daily dose: 1,000 mg/day. Note: Ethionamide causes nausea and patients are often unable to tolerate the maximum dose divided twice daily (eg, in adults, 500 mg twice daily); therefore, experts suggest beginning with a low once daily dose and gradually increasing as tolerated; may consider therapeutic drug monitoring to aid in determining appropriate dose

Healthcare provider may recommend an increase in dietary intake of pyridoxine to prevent neurotoxic effects of ethionamide. Avoid alcohol.

Hypersensitivity to Ethionamide or other quinolone antibiotics. Patient with history of tendon disorders, myasthenia gravis, QT interval prolongation, ventricular arrhythmias, proarrhythmic conditions (e.g. bradycardia, acute MI), peripheral neuropathy, uncorrected electrolyte disorders (e.g. hypokalaemia, hypomagnesemia). Concomitant use with Class 1A and Class III antiarrhythmics, antihistamines, and other drugs that prolong QT interval (e.g. cisapride, erythromycin, antipsychotics, and TCA).

Concerns related to adverse effects:

• Dermatologic reactions: Cases of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms syndrome have been reported. Discontinue treatment immediately and institute appropriate therapy if signs or symptoms of SCAR develop.

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus; may cause hypoglycemia.

• Hepatotoxicity: May cause hepatotoxicity; monitor liver function tests at baseline and monthly.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction; hypothyroidism (reversible; with and without goiter) has been reported.

Other warnings/precautions:

• Appropriate use: Drug-resistant tuberculosis develops rapidly if ethionamide is used alone; must administer with other antituberculosis agents. Directly observed therapy (DOT) is recommended.
• Ethanol use: Avoid excessive ethanol intake; psychotic reaction may occur.
• Eye exams: Eye exams are recommended at baseline and periodically during therapy.

Ethionamide may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Absorption is not affected by administration with a high-fat meal or yogurt.

• Common Adverse effects

Psychotic disturbances, mental depression, anxiety, drowsiness, dizziness, restlessness, headache, peripheral neuritis, paraesthesia, seizures, tremors, pellagra-like syndrome, hallucination

• Less Common Adverse effects:

Nausea, vomiting, diarrhea, abdominal pain, excessive salivation, metallic taste, stomatitis, anorexia, wt loss., Olfactory disturbances. Hepatic: Hepatitis, transient increase in serum bilirubin

• Rare Adverse effects

Diplopia, optic neuritis, blurred vision. Dermatologic: Rash, photosensitivity, purpura, acne, dermatitis, alopecia.

May potentiate Adverse reactions of other anti-TB drugs. Additive CNS effect w/ isoniazid and cycloserine. May cause seizures w/ cycloserine.

The common side effects of Ethionamide include the following nausea; diarrhea; headache; vomiting; dizziness; nervousness; agitation; nightmares

Pharmacodynamic

Ethionamide is a DNA gyrase inhibitor, and also inhibits topoisomerase IV. DNA gyrase (topoisomerase II) is an essential bacterial enzyme that maintains the superhelical structure of DNA. DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; inhibition is bactericidal.

Pharmacokinetics

• Absorption: Readily absorbed from the GI tract. Time to peak serum concentration: Approx 1 hr.
• Distribution: Widely distributed throughout body tissues and fluids. Crosses placenta and CSF. Volume of distribution: 93.5 L. Plasma protein binding: 30%.
• Metabolism: Extensively metabolised in the liver to the active metabolite sulfoxide and some inactive metabolites.
• Excretion: Via urine (<1% as unchanged drug). Elimination half-life: Approx 2 hr.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
• https://reference.medscape.com/drug/colestid-Ethionamide -342452
• https://go.drugbank.com/drugs/DB00375
• https://www.sciencedirect.com/topics/medicine-and-dentistry/Ethionamide
• https://europepmc.org/article/med/6988203