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Ethionamide

Medically reviewed by Drugs.com. Last updated on Aug 17, 2020.

Pronunciation

(e thye on AM ide)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Trecator: 250 mg [contains fd&c yellow #6 (sunset yellow)]

Brand Names: U.S.

  • Trecator

Pharmacologic Category

  • Antitubercular Agent

Pharmacology

Inhibits peptide synthesis; bacteriostatic

Absorption

Essentially complete absorption

Distribution

Vd: 93.5 L; widely distributed into body tissues and fluids including CSF

Metabolism

Prodrug; extensively hepatic to active and inactive metabolites

Excretion

Urine (<1% as unchanged drug; as active and inactive metabolites)

Time to Peak

Serum: ~1 hour

Half-Life Elimination

~2 hours

Protein Binding

~30%

Use: Labeled 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.

Contraindications

Hypersensitivity to ethionamide or any component of the formulation; severe hepatic impairment

Dosing: Adult

Tuberculosis, drug resistant (alternative agent): Note: Expert consultation for optimal regimen and duration of treatment is advised; coadministration of pyridoxine is recommended for prevention of neurotoxic effects.

Oral: 15 to 20 mg/kg/day in 1 or 2 divided doses (usually 250 or 500 mg once or twice daily) in combination with additional appropriate antituberculosis agents. Some experts recommend starting with 250 mg once daily and gradually increasing over 1 week; few patients tolerate 500 mg twice daily (maximum daily dose: 1 g/day) (ATS/CDC/ERS/IDSA [Nahid 2019]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Active TB 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 (ATS/CDC/IDSA [Nahid 2016]). 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/-positive, 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 (ATS/CDC/IDSA [Nahid 2016]; HHS [OI pediatric 2020]; Seddon 2012).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Directly observed therapy is recommended. Administer with or without meals. GI adverse effects may be decreased by administration at meals or bedtime, decreased dose, or giving with antiemetics.

Dietary Considerations

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

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Alcohol (Ethyl): May enhance the adverse/toxic effect of Ethionamide. Specifically, there may be a risk for a psychotic episode/reaction. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

CycloSERINE: Ethionamide may enhance the adverse/toxic effect of CycloSERINE. Monitor therapy

Isoniazid: Ethionamide may increase the serum concentration of Isoniazid. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Orthostatic hypotension

Dermatologic: Acne vulgaris, skin photosensitivity, skin rash

Endocrine & metabolic: Goiter, gynecomastia, hypoglycemia, hypothyroidism, pellagra (pellagra-like syndrome), weight loss

Gastrointestinal: Abdominal pain, anorexia, diarrhea, nausea, sialorrhea, stomatitis, vomiting

Genitourinary: Impotence

Hematologic & oncologic: Purpuric disease, thrombocytopenia

Hepatic: Hepatitis, increased serum alanine aminotransferase, increased aspartate aminotransferase, increased serum bilirubin, jaundice

Hypersensitivity: Hypersensitivity reaction

Nervous system: Depression, dizziness, drowsiness, headache, metallic taste, peripheral neuritis, psychiatric disturbance, restlessness

Ophthalmic: Blurred vision, diplopia, optic neuritis

Warnings/Precautions

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.

• Porphyria: Use not recommended; porphyria-inducing in animal and in vitro studies (WHO 2008).

• 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.

Monitoring Parameters

Baseline and monthly serum ALT and AST; baseline and periodic ophthalmic exams; periodic blood glucose and TSH; signs and symptoms of severe cutaneous adverse reactions.

Reproductive Considerations

Evaluate pregnancy status prior to treatment of multidrug resistant tuberculosis in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug resistant tuberculosis (Esmail 2018).

Pregnancy Considerations

Based on data from animal reproduction studies and limited human data, in utero exposure to ethionamide may cause fetal harm (HHS [OI 2020]). In addition, ethionamide may increase the risk of nausea and vomiting in pregnant patients (Esmail 2018).

Active tuberculosis infection is associated with adverse fetal outcomes including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020) as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).

Data is limited for use of second line drugs during pregnancy (ie, ethionamide) (ATS/CDC/ERS/IDSA [Nahid 2019]). The treatment of multidrug resistant tuberculosis in pregnant patients should be individualized; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020). Use of ethionamide should be avoided when possible (HHS [OI 2020]).

Patient Education

What is this drug used for?

• It is used to treat TB (tuberculosis).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Stomach pain or diarrhea

• Upset stomach or throwing up

• More saliva

• Restlessness

• Metallic taste

• Mouth irritation or mouth sores

• Feeling sleepy

• Not hungry

• Weight loss

• Dizziness or headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Low thyroid level like constipation; not able to handle cold; memory problems; mood changes; or a burning, numbness, or tingling feeling that is not normal

• Lump on your neck

• Very bad dizziness or passing out

• Depression or other mood changes

• Change in eyesight, eye pain, or very bad eye irritation

• Loss of eyesight

• Fever

• Swollen gland

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Low blood sugar like dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.