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Ethionamide: Drug information

Ethionamide: Drug information
(For additional information see "Ethionamide: Patient drug information" and see "Ethionamide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Trecator
Pharmacologic Category
  • Antitubercular Agent
Dosing: Adult
Tuberculosis, drug resistant

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: Kidney Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling; however, the following adjustments have been reported in the literature (ATS/CDC/IDSA [Nahid 2016]):

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: 250 to 500 mg/day.

End-stage renal disease (ESRD) on hemodialysis: 250 to 500 mg/day.

Dosing: Hepatic Impairment: Adult

Mild or moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution (ATS/CDC/IDSA [Blumberg 2003]).

Severe impairment: Use is contraindicated.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Ethionamide: Pediatric drug information")

Active tuberculosis infection, treatment

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 (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/-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 (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.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer labeling nor recommendations specific for pediatric patients; experience in adult patients suggests that dosage adjustment may be necessary.

Dosing: Hepatic Impairment: Pediatric

Mild or moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution (Blumberg 2003).

Severe impairment: Use is contraindicated.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions may be from combination antituberculosis regimens.

Frequency not defined:

Cardiovascular: Orthostatic hypotension

Dermatologic: Acne vulgaris, acute generalized exanthematous pustulosis, skin photosensitivity, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis

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

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

Genitourinary: Erectile dysfunction

Hematologic & oncologic: Purpuric disease, thrombocytopenia

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

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms, hypersensitivity reaction

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

Ophthalmic: Blurred vision, diplopia, optic neuritis

Contraindications

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

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.

• 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.

Dosage Forms: US

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)]

Generic Equivalent Available: US

No

Pricing: US

Tablets (Trecator Oral)

250 mg (per each): $6.73

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

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.

Administration: Pediatric

Oral: Administer with meals or at bedtime to decrease GI distress (nausea)

Use: Labeled Indications

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

Medication Safety Issues
Sound-alike/look-alike issues:

Ethionamide may be confused with ethosuximide.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

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

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: 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. Risk X: Avoid combination

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

Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination

Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

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

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

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).

Tuberculosis (TB) disease (active TB) 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 are limited for use of second line drugs during pregnancy (ie, ethionamide) (ATS/CDC/ERS/IDSA [Nahid 2019]). The treatment of multidrug resistant TB 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]).

Breastfeeding Considerations

It is not known if ethionamide is present in breast milk.

If ethionamide is used while breastfeeding, monitor the infant for adverse effects. Patients with multidrug resistant tuberculosis and a sputum smear-positive test should avoid breastfeeding when possible (Esmail 2018).

Dietary Considerations

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

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; ethionamide serum concentrations (when clinically indicated).

Reference Range

Note: Obtain samples at 2 and 6 hours post dose to detect delayed absorption or malabsorption (Peloquin 2002).

Therapeutic peak levels: 1 to 5 mcg/mL after a 250 to 500 mg dose (Peloquin 2002).

Mechanism of Action

Inhibits peptide synthesis; bacteriostatic

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Essentially complete absorption

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

Protein binding: ~30%

Metabolism: Prodrug; extensively hepatic to active and inactive metabolites

Half-life elimination: ~2 hours

Time to peak, serum: ~1 hour

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Trecator;
  • (BR) Brazil: Farmanguinhos etionamida;
  • (FI) Finland: Nicotion;
  • (FR) France: Trecator;
  • (GR) Greece: Ethatyl | Trecator;
  • (IE) Ireland: Trecator;
  • (IN) India: E-thio | Ethide | Ethimax | Ethiobin | Ethiocid | Ethomid | Etomide | Etumide | Mycotuf | Myobid | Thiomid e;
  • (JP) Japan: Ethimide | Ethinamin | Ethionamide yamanouchi | Itiocide | Sertinon | Teberus | Thioniden | Tubermin | Tuberoson;
  • (KE) Kenya: Ethomid;
  • (MY) Malaysia: Ethomid;
  • (PE) Peru: Ethiocol | Etionamida;
  • (PK) Pakistan: Ethomid;
  • (PL) Poland: Etionamid | Thiomid e | Trecator sc | Tumid;
  • (PR) Puerto Rico: Trecator;
  • (PT) Portugal: Etionamida | Trecator sc;
  • (RO) Romania: Etionamida atb;
  • (RU) Russian Federation: Ethomid | Etid | Myobid | Reginicid;
  • (TH) Thailand: Eton;
  • (TN) Tunisia: Trecator;
  • (UA) Ukraine: Ethionamid | Ethomid;
  • (UG) Uganda: Ethomid;
  • (ZA) South Africa: Ethatyl | Ethionamide macleods;
  • (ZM) Zambia: Ethide | Ethomid
  1. Arbex MA, Varella Mde C, de Siqueira HR, et al, "Antituberculosis Drugs: Drug Interactions, Adverse Effects, and Use in Special Situations. Part 2: Second-Line Drugs," J Bras Pneumol, 2010, 36(5):641-56. [PubMed 21085831]
  2. Blumberg HM, Burman WJ, Chaisson RE, et al, “American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis,” Am J Respir Crit Care Med, 2003, 167(4):603-62. [PubMed 12588714]
  3. Centers for Disease Control and Prevention (CDC), "Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children," MMWR Recomm Rep, 2009, 58(RR-11):1-166. [PubMed 19730409]
  4. Centers for Disease Control and Prevention, “Treatment of Tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society of America,” MMWR Recomm Rep, 2003, 52(RR11);26, 64.
  5. Donald PR and Seifart HI, “Cerebrospinal Fluid Concentrations of Ethionamide in Children With Tuberculous Meningitis,” J Pediatr, 1989, 115(3):483-6. [PubMed 2769511]
  6. Esmail A, Sabur NF, Okpechi I, Dheda K. Management of drug-resistant tuberculosis in special sub-populations including those with HIV co-infection, pregnancy, diabetes, organ-specific dysfunction, and in the critically ill. J Thorac Dis. 2018;10(5):3102-3118. doi:10.21037/jtd.2018.05.11 [PubMed 29997980]
  7. HHS Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Department of Health and Human Services. November 2013. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/pediatric-oi/tables-pediatric-oi.pdf. Accessed June 2020.
  8. Miele K, Bamrah Morris S, Tepper NK. Tuberculosis in pregnancy. Obstet Gynecol. 2020;135(6):1444-1453. doi:10.1097/AOG.0000000000003890 [PubMed 32459437]
  9. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147-195. [PubMed 27516382]
  10. Nahid P, Mase SR, Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med. 2019;200(10):e93-e142. doi:10.1164/rccm.201909-1874ST [PubMed 31729908]
  11. Pattyn SR, Janssens L, Bourland J, et al, “Hepatotoxicity of the Combination of Rifampin-Ethionamide in the Treatment of Multibacillary Leprosy,” Int J Lepr Other Mycobact Dis, 1984, 52(1):1-6. [PubMed 6368424]
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  15. Trecator (ethionamide) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; July 2020.
  16. Trecator (ethionamide) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; July 2023.
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