Ethomid

Ethomid is yellow, circular, deep biconvex, film-coated tablets having plain surface on both sides.
Each film-coated tablet contains Ethionamide 250 mg.
It is composed of ethionamide which is used in the treatment of tuberculosis. The chemical name for ethionamide is 2-ethylthioisonicotinamide. Its molecular formula is C₈H₁₀N₂S and its molecular mass is 166.244 g/mol.

Pharmacology: Pharmacodynamics: 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. Ethionamide is active in vitro and in vivo against M. tuberculosis, M. bovis, M. kansasii, and some strains of M. avium complex (MAC) and M. intracellulare.
Pharmacokinetics: Absorption: Ethionamide is essentially completely absorbed following oral administration. Following a single 250 mg oral dose of ethionamide given as film-coated tablets in fasting adults, peak plasma concentrations of ethionamide average 2.16 mcg/mL and are attained within 1 hour.
Distribution: The mean apparent oral volume of distribution reported in healthy adults is 93.5 L. Ethionamide is about 30% bound to plasma proteins.
Elimination: The plasma half-life of ethionamide is approximately 1.92 hrs. Ethionamide is extensively metabolized to active and inactive metabolites, probably in the liver. At least 6 metabolites have been identified; the sulfoxide metabolite is active against Mycobacterium tuberculosis. Less than 1% of an oral dose of ethionamide is excreted in urine as active drug and metabolites; the remainder is excreted in urine as inactive metabolites. Only low concentrations of ethionamide are removed by hemodialysis.

Ethionamide is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis.
Ethionamide is considered a second-line antituberculosis agent for use in these regimens. The drug usually is used in the treatment of drug-resistant tuberculosis caused by Mycobacterium tuberculosis known or presumed to be susceptible to the drug, especially when isoniazid and/or rifampin cannot be used because of resistance and/or intolerance.

Recommended Dose: Ethionamide is administered orally without regard to meals. Ethionamide usually is administered once daily, but may be given in divided doses if GI intolerance occurs. If ethionamide is given as a single daily dose, it should be given at the time of day that the patient find most suitable in order to avoid or minimize GI intolerance.
Adult dosage: For use in conjunction with other antituberculosis agents for the treatment of active tuberculosis in adults, the usual dosage of ethionamide is 15-20 mg/kg daily. The recommended initial dosage is 250 mg daily, with gradual titration to optimal dosage based on patient tolerance (Maximum dose: 1 g/day).
Pediatric dosage: The optimum pediatric dosage has not been established, but dosages of 10-20 mg/kg daily given in 2 or 3 divided doses after meals or 15 mg/kg once daily have been recommended for children.
Hepatic impairment: Ethionamide is almost completely metabolised in the liver. Its use should be avoided in patients with severe hepatic impairment and should be used with caution in patients with less severe hepatic impairment.
Renal impairment: Although some clinicians state that dosage adjustments are not necessary in patients with renal impairment, others state that ethionamide dosage should be reduced to 250-500 mg daily in patients with creatinine clearance less than 30 mL/minute and in those undergoing hemodialysis.
Duration of therapy: Therapy for tuberculosis should be continued long enough to prevent relapse. The minimum duration of treatment currently recommended for patients with culture-positive pulmonary tuberculosis is 6 months (26 weeks) and recommended regimens consist of an initial intensive phase (2 months) and a continuation phase (usually either 4 or 7 months). Duration of treatment should be based on individual clinical response. In general, continue therapy until bacteriological conversion has become permanent and maximal clinical improvement has occurred.
Mode of Administration: Orally.

Overdose and Treatment: If overdosage of ethionamide occurs, standard procedures to evacuate gastric contents and supportive care should be employed. Only low concentrations of ethionamide are removed by hemodialysis.

In patients with severe hepatic impairment and in patients who are hypersensitive to the drug.

Resistance: The use of ethionamide alone in the treatment of tuberculosis results in rapid development of resistance. It is essential, therefore, to give a suitable companion, the choice being based on results of susceptibility testing. However, therapy may be initiated prior to receiving the results of susceptibility tests as deemed appropriate by the physician.
Liver toxicity: Serum AST (SGOT) and ALT (SGPT) concentration should be determined prior to and at monthly intervals during ethionamide therapy. If serum transaminases become elevated during ethionamide therapy, the drug and concomitant antituberculosis agents may be discontinued temporarily until laboratory abnormalities resolve. Ethionamide and concomitant antituberculosis drugs should then be reintroduced sequentially to determine which drug(s) is responsible for the hepatotoxicity.
Neurological effects: Psychotic disturbances, mental depression, restlessness, drowsiness, dizziness, headache, postural hypotension, and asthenia occur occasionally with ethionamide. Rarely, peripheral neuritis, paresthesia, seizures, tremors, a pellagra-like syndrome, hallucinations, diplopia, optic neuritis, blurred vision, and olfactory disturbances have been reported. It recommends concomitant use of pyridoxine to prevent or relieve neurotoxic effects during ethionamide treatment.
Blood glucose: Blood glucose concentrations should be determined prior to and periodically during ethionamide therapy. The management of patients with diabetes mellitus may become more difficult during ethionamide therapy. Diabetic patients should be particularly alert for hypoglycemic episodes.
Hypothyroidism: Thyroid function tests should be monitored periodically (e.g., at baseline and at monthly intervals) since hypothyroidism, with or without goiter, has been reported during ethionamide therapy.
Allergic reactions: Hypersensitivity reactions including rash, photosensitivity, thrombocytopenia, and purpura have been reported rarely with ethionamide.

Pregnancy Category: C.
Safe use of ethionamide during pregnancy has not been established. The drug has caused teratogenic effects in rabbits and rats when administered in high doses. There are no adequate and controlled studies to date using ethionamide in pregnant women, and it is stated that the drug should not be used in women who are or may become pregnant unless the clinician considers the drug essential to treatment.
The effect to ethionamide on labor and delivery in pregnant women is unknown. Because it is not known whether ethionamide is distributed into human milk, the drug should be administered to nursing mothers only if the benefits of therapy outweighs the potential risks to the infant. It is stated that if ethionamide is administered during breastfeeding, the infant should be monitored for adverse effects.

CNS: Psychotic disturbances (including mental depression), drowsiness, dizziness, restlessness, headache, and postural hypotension have been reported with ethionamide. Rare reports of peripheral neuritis, optic neuritis, diplopia, blurred vision, and a pellagra-like syndrome also have been reported. Concurrent administration of pyridoxine has been recommended to prevent or relieve neurotoxic effects.
GI: The most common side effects of ethionamide are gastrointestinal disturbances including nausea, vomiting, diarrhea, abdominal pain, excessive salivation, metallic taste, stomatitis, anorexia and weight loss.
Adverse gastrointestinal effects appear to be dose related, with ~50% of patients unable to tolerate 1 g as a single dose. Gastrointestinal effects may be minimized by decreasing dosage, by changing the time of drug administration, or by the concurrent administration of an antiemetic agent.
Hepatic: Transient increases in serum bilirubin, AST, ALT; hepatitis (with or without jaundice).
Hypersensitivity: Hypersensitivity reactions including rash, photosensitivity, thrombocytopenia and purpura have been reported rarely.
Miscellaneous: Hypoglycemia, gynecomastia, impotence, and acne also have occurred. The management of patients with diabetes mellitus may become more difficult in those receiving ethionamide.

Alcohol: Patients receiving ethionamide should avoid excessive ingestion of alcohol because a psychotic reaction has been reported in this situation.
Antituberculosis agents: Serum concentrations of isoniazid may increase temporarily during concomitant ethionamide therapy. Ethionamide may potentiate the adverse effects of other antituberculosis agents included in the treatment regimen. There is some evidence that adverse nervous system effects of ethionamide, cycloserine, and isoniazid may be additive. Seizures have been reported in patients receiving regimen that included both ethionamide and cycloserine and caution is advised if these drugs are used concomitantly.

Storage Condition: Do not store above 30°C. Protect from light.

Anti-TB Agents

J04AD03 - ethionamide ; Belongs to the class of thiocarbamide derivatives. Used in the systemic treatment of tuberculosis.

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