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Ethionamide

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: Oral:

Manufacturer’s labeling: 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)

Alternate dosing: 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).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Tuberculosis: Children and Adolescents: Oral:

Manufacturer’s labeling: 10 to 20 mg/kg/day in 2 to 3 divided doses or 15 mg/kg/day as a single daily dose.

Alternate recommendations: 15 to 20 mg/kg/day in 1 to 2 divided doses (maximum daily dose: 1,000 mg/day) (HHS OI [pediatric] 2013; WHO 2008)

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer's labeling; however, the following adjustments for adults have been reported in the literature (Blumberg 2003; WHO 2008):

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

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.

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. 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 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, headache, agitation, metallic taste, mouth irritation, mouth sores, fatigue, drooling, 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 jaundice), 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, tachycardia, 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.

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