Ethionamide is a second-line drug used to treat patients with tuberculosis. It is indicated in patients with multidrug resistant tuberculosis or those who are intolerant to other antituberculosis drugs. It is usually given in combination with other second line medications including an injectable (aminoglycoside such as amikacin, capreomycin, or kanamycin) in the treatment of multidrug resistant tuberculosis.

Ethionamide Uses:

• Tuberculosis:

  • It is intended for the treatment of tuberculosis in patients who are intolerant to other medications or who have developed multidrug resistance. It is administered along with other antituberculous medications.

Ethionamide Dose in Adults

Dose in the treatment of Tuberculosis as a second-line agent: Oral:

• 15 to 20 mg/kg/day orally one one or two divided doses.
• The usual daily dose is 500 to 750 mg/day.
• The highest daily dose advised is 1000 mg.

• Manufacturer’s labeling:

  • The dose recommendations given by the manufacturer may not reflect the current clinical practice guidelines.
  • The manufacturer recommends giving it at a dose of 15 to 20 mg/kg per day.
  • The typical starting dose for the treatment is 250 mg once daily for 2 to 3 days. The dose is then increased to the recommended dose by 250 mg per day, divided into two doses, every third day.
  • the average adult dose is 750 mg/day.
  • The maximum daily recommended dose is 1000 mg administered in two or three divided doses.

Ethionamide Dose in Children

Ethionamide Dose as a second-line treatment of Active Tuberculosis excluding meningitis:

Note: It should be used as a part of multidrug regimen. An infectious disease expert may be consulted prior to using second-line drugs to make an effective second line tuberculosis regimen.

• Infants, Children, and Adolescents:

  • Oral administration of 15–20 mg/kg/day in one or two split doses.
  • The usual adult dose is 250 - 500 mg per dose to a maximum daily dose of 1000 mg.
  • In HIV infected or exposed patients, the dose may be administered in two or three equally divided doses.

Note:

• The drug may not be tolerated when given in full strength i.e. 500 mg two times a day. It is therefore recommended that a low once daily dose may be initiated and gradually titrated to the required daily dose.
• Some experts recommend measuring drug levels for appropriate dose.

Pregnancy Risk Category: N (Not assigned)

• The drug crosses the placental boundary.
• It is not recommended to be used during pregnancy.

Use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• Breastfeeding should not be interrupted if the drug is necessary.

Ethionamide Dose in Kidney Disease:

• The manufacturer has not recommended any adjustment in the dose, however, the following dose adjustments may be made:
• CrCl ≥30 mL/minute:
  • Adjustment in the dose is not necessary.
• CrCl <30 mL/minute:
  • 250 to 500 mg/day
• End-stage renal disease (ESRD) on hemodialysis:
  • 250 to 500 mg/day

Ethionamide Dose in Liver disease:

• Mild or moderate impairment:

  • The manufacturer has not recommended any adjustments in the dose, however, it should be used with caution.

• Severe impairment:

  • In severe liver disease, the drug is contraindicated.

Side effects of ethionmide:

• Cardiovascular:

  • Orthostatic Hypotension

• Central Nervous System:

  • Altered Sense Of Smell
  • Depression
  • Dizziness
  • Drowsiness
  • Headache
  • Metallic Taste
  • Peripheral Neuritis
  • Psychiatric Disturbance
  • Restlessness
  • Seizure

• Dermatologic:

  • Acne Vulgaris
  • Alopecia
  • Purpura
  • Skin Photosensitivity
  • Skin Rash

• Endocrine & Metabolic:

  • Goiter
  • Gynecomastia
  • Hypoglycemia
  • Hypothyroidism
  • Menstrual Disease
  • Pellagra (Pellagra-Like Syndrome)
  • Weight Loss

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Diarrhea
  • Sialorrhea
  • Nausea
  • Stomatitis
  • Vomiting

• Genitourinary:

  • Impotence

• Hematologic & Oncologic:

  • Leukopenia
  • Thrombocytopenia

• Hepatic:

  • Hepatitis
  • Increased Liver Enzymes
  • Increased Serum Bilirubin
  • Jaundice

• Hypersensitivity:

  • Hypersensitivity Reaction

• Neuromuscular & Skeletal:

  • Arthralgia

• Ophthalmic:

  • Blurred Vision
  • Diplopia
  • Optic Neuritis

Contraindications to Ethionamide:

• Allergy reactions to the drug, or any component thereof;
• Grave hepatic impairment

Warnings and precautions

• Diabetes:

  • It can cause hypoglycemia.
  • Diabetes patients may be advised to take the drug with caution.

• Hepatotoxicity:

  • It can cause hepatotoxicity.
  • Liver function tests ought to be carried out in the beginning.

• Porphyria

  • Porphyria patients should stay away from it.

• Thyroid dysfunction:

  • Hypothyroidism may be caused by its use.
  • Patients suffering from thyroid dysfunction should be cautious when taking the drug.

Monitoring parameters:

• Liver functions tests at baseline and monthly thereafter.
• Ophthalmic examination at baseline and periodically thereafter as required.
• Blood glucose and TSH levels periodically.

Ethionamide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

How to administer Ethionamide?

• It may be administered with or without meals. To reduce the gastrointestinal side effects of the drug, it may be administered with meals or administered with antiemetic drugs.
• It should be administered with vitamin B6 (Pyridoxine) to prevent the neurotoxicity associated with its use.
• It should be preferably administered as a DOT therapy (directly observed therapy).

Mechanism of action of Ethionamide:

It acts as a bacteriostatic (a nicotinic Acid derivative) by inducing bacterial peptide production.

Absorption:

• It is almost entirely absorbed.

Distribution:

• It is found in body fluids, including the cerebrospinal fluid, and tissues.

Protein binding:

• About 30%

Metabolism:

• It is a prodrug.
• The drug is extensively metabolized in the liver to active and inactive metabolites

Half-life elimination:

• About 2 hours

Time to peak, serum concentration:

• About one hour

Excretion:

• Urine (<1% of the drug is excreted as unchanged drug or as metabolites)

International Brand Names of Ethionamide:

• Trecator
• Enamide
• Enazmide
• Ethatyl
• Ethiobin
• Ethiocol
• Ethomid
• Eton-250
• Mycotuf
• Myobid-250
• Trecator
• Tumid

Ethionamide Brand Names in Pakistan: