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)]
Pharmacology
Mechanism of Action
Inhibits peptide synthesis; bacteriostatic
Pharmacokinetics/Pharmacodynamics
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
Dosage and Administration
Dosing: Adult
Tuberculosis: Oral:
15 to 20 mg/kg/day in 1 or 2 divided doses (usually 500 to 750 mg/day; maximum daily dose: 1 g/day) (Blumberg 2003).
Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. 15 to 20 mg/kg/day; initiate dose at 250 mg daily for 1 to 2 days, then increase to 250 mg twice daily for 1 to 2 days, with gradual increases to highest tolerated dose; average adult dose: 750 mg/day (maximum daily dose: 1 g/day in 3 to 4 divided doses)
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]). 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 2016], Seddon 2012)
Administration
Directly observed therapy (DOT) is recommended. Neurotoxic effects may be prevented or relieved by the coadministration of pyridoxine (see Pyridoxine monograph for dosing). Administer with or without meals. Gastrointestinal 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: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Adverse Reactions
Frequency not defined.
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
Warnings/Precautions
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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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
Pregnancy
Pregnancy Considerations
Ethionamide crosses the placenta. Use during pregnancy is not recommended (Blumberg 2003).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience abdominal pain, nausea, vomiting, diarrhea, increased saliva, headache, agitation, metallic taste, mouth irritation, mouth sores, fatigue, lack of appetite, or weight loss. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of a low thyroid level (constipation; difficulty handling heat or cold; memory problems; mood changes; or burning, numbness, or tingling feeling), neck lump, severe dizziness, passing out, depression, vision changes, eye pain, severe eye irritation, blindness, mood changes, behavioral changes, or signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
