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ETHIONAMIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Ethionamide is a thioamide derivative.

Specific Substances

    1) Ethionamidum
    2) Etionamida
    3) 3-ethylisothionicotinamide
    4) 2-ethylisothionicotinamide
    5) 2-ethyl-4-thiocarbamoylpyridine
    6) alpha-ethylisonicotinoylthioamide
    7) amidazine
    8) Molecular Formula: C8-H10-N2-S
    9) CAS 536-33-4
    10) 1314 TH
    11) BAYER 5312
    12) TH 1314
    1.2.1) MOLECULAR FORMULA
    1) C8H10N2S

Available Forms Sources

    A) FORMS
    1) Ethionamide is available as 250 mg tablets (Prod Info Trecator(R) oral film coated tablets, 2013).
    B) USES
    1) Ethionamide is an antituberculosis drug used as second-line therapy only in combination with other efficacious agents and only when therapy with isoniazid, rifampin, or other first-line agents has failed (Prod Info Trecator(R) oral film coated tablets, 2013).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Ethionamide is an antituberculosis drug used as second-line therapy only in combination with other efficacious agents and only when therapy with isoniazid, rifampin, or other first-line agents has failed.
    B) PHARMACOLOGY: The exact mechanism has not been fully established, but the bacteriostatic and bactericidal action of ethionamide is thought to be due to inhibition of peptide synthesis in the infecting organism.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: COMMON: Nausea, vomiting, diarrhea, headache, alopecia, metallic taste, and rashes. LESS COMMON: Encephalopathy, psychosis, headache, paresthesias, somnolence, hypothyroidism, elevated liver enzymes, thrombocytopenia, hypoglycemia, and insomnia.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: There are no reports of toxicity following acute overdose. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Encephalopathy, psychosis, headache, paresthesias, somnolence, and insomnia are uncommon effects at therapeutic doses.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, and diarrhea are common adverse events at therapeutic doses. Anorexia, abdominal pain, and taste disturbances occur less frequently.
    0.2.9) HEPATIC
    A) WITH THERAPEUTIC USE
    1) Increased liver enzyme levels have been reported in patients as an adverse effect.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Various types of rashes, as well as alopecia, have been reported following therapeutic doses.
    0.2.20) REPRODUCTIVE
    A) Use of the drug should be avoided during pregnancy or in women of childbearing potential unless the benefits outweigh its potential hazards.
    B) Developmental anomalies occured in women who received ethionamide during pregnancy; including congenital heart disease, spina bifida, spinal anomalies, Down's syndrome and possible hydrocephalus.

Laboratory Monitoring

    A) Monitor liver enzyme levels after significant overdose.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Case reports suggest that pyridoxine and nicotinamide may be useful in ethionamide-induced encephalopathy.
    C) DECONTAMINATION
    1) PREHOSPITAL: Consider activated charcoal if recent, substantial ingestion and the patient is able to protect the airway.
    2) HOSPITAL: Consider activated charcoal if resent substantial ingestion and the patient is able to protect the airway.
    D) ANTIDOTE
    1) None.
    E) DISORDER OF BRAIN
    1) Pyridoxine and nicotinamide have been recommended to lessen the effects of encephalopathy, but there are no studies supporting efficacy. Doses of 100 to 150 mg/day of pyridoxine and 150 mg/day of nicotinamide have been used.
    F) ENHANCED ELIMINATION
    1) Hemodialysis can remove approximately 2% of a therapeutic dose; however, its place in the management of ethionamide overdose has not been determined.
    G) PATIENT DISPOSITION
    1) OBSERVATION CRITERIA: All patients with overdose ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve.
    2) ADMISSION CRITERIA: Patients demonstrating severe encephalopathy should be admitted.
    3) CONSULT CRITERIA: Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    H) PITFALLS
    1) When managing a suspected ethionamide overdose, the possibility of coingestants should be considered.
    I) PHARMACOKINETICS
    1) Oral absorption is nearly complete, maximum serum concentrations are reached in approximately 1 hour after administration. Ethionamide is approximately 30% protein bound and has a mean volume of distribution of 93.5 L. It is extensively metabolized in the liver and the mean half-life is approximately 1.9 hours (SD=0.27).
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes other antituberculosis agents that may cause encephalopathy (eg, isoniazid).

Range Of Toxicity

    A) The toxic dose of ethionamide is not established. Adults have tolerated single oral doses of 90 mg/kg.

Clinical Effects

Summary Of Exposure

    A) USES: Ethionamide is an antituberculosis drug used as second-line therapy only in combination with other efficacious agents and only when therapy with isoniazid, rifampin, or other first-line agents has failed.
    B) PHARMACOLOGY: The exact mechanism has not been fully established, but the bacteriostatic and bactericidal action of ethionamide is thought to be due to inhibition of peptide synthesis in the infecting organism.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: COMMON: Nausea, vomiting, diarrhea, headache, alopecia, metallic taste, and rashes. LESS COMMON: Encephalopathy, psychosis, headache, paresthesias, somnolence, hypothyroidism, elevated liver enzymes, thrombocytopenia, hypoglycemia, and insomnia.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: There are no reports of toxicity following acute overdose. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) Visual disturbances have been reported with therapeutic use (Fox et al, 1969).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Encephalopathy, psychosis, headache, paresthesias, somnolence, and insomnia are uncommon effects at therapeutic doses.
    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Swash et al (1972) described 3 patients who developed encephalopathy while taking ethionamide in conjunction with other drugs (isoniazid in 2 patients, cycloserine and ethambutol in the third). Effects included confusion, irritability, incontinence, difficulty standing and walking, ataxia, slowed mentation, and abnormal reflexes (suck, grasp, jaw jerk, brisk tendon reflexes). All 3 patients improved after treatment with vitamins (nicotinamide 100 to 150 milligrams/day; pyridoxine and a parenteral multiple vitamin preparation).
    b) CASE REPORT: A 36-year-old man with a history of significant ethanol abuse developed leg weakness, difficulty speaking, ataxia, decreased responsiveness, and organic brain syndrome while taking ethionamide, isoniazid, and streptomycin (Lansdown et al, 1967). He improved within 8 days after his antituberculosis drugs were discontinued and vitamin supplements were started.
    B) PSYCHOTIC DISORDER
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 30-year-old man developed violent behavior, incoherence, and disorientation while taking ethionamide, pyrazinamide, streptomycin and isoniazid, and pyridoxine (Narang, 1972).
    b) CASE REPORT: A 16-year-old developed restlessness, incoherence, confusion, and violent behavior 1 day after beginning therapy with streptomycin, isoniazid, and thiacetazone (Sharma et al, 1979). He was treated with pyridoxine and a sedative; his antituberculosis drugs were withdrawn and he improved. His symptoms did not recur when streptomycin was resumed but recurred with isoniazid. Symptoms recurred again when he was treated with ethionamide, PAS and ethambutol, although he later tolerated therapy with PAS and ethambutol.
    C) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache has been reported with therapeutic use (Gupta, 1977; Gupta et al, 1975; Fox et al, 1969; Simon et al, 1969; Anon, 1968) .
    D) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) Paresthesias have been reported with therapeutic use (Gupta, 1977; Gupta et al, 1975; Anon, 1968).
    E) DROWSY
    1) WITH THERAPEUTIC USE
    a) Sleepiness has been reported with therapeutic use; in some cases it has been severe enough to withdraw therapy (Gupta, 1977; Gupta et al, 1975; Anon, 1968) .
    F) TREMOR
    1) WITH THERAPEUTIC USE
    a) Weakness and tremor have been reported with therapeutic use (Simon et al, 1969).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, and diarrhea are common adverse events at therapeutic doses. Anorexia, abdominal pain, and taste disturbances occur less frequently.
    3.8.2) CLINICAL EFFECTS
    A) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) WITH THERAPEUTIC USE
    a) Nausea, vomiting, diarrhea, abdominal pain, excessive salivation, stomatitis, anorexia, and weight loss are the most common side effects of ethionamide. These effects appear to be dose related, with approximately 50% of patients unable to tolerate 1 gram as a single dose (Prod Info TRECATOR(R) oral tablets, 2005; Donald et al, 1987; Gupta, 1977; Devadatta et al, 1970; Fox et al, 1969; Anon, 1968) .
    b) Abdominal discomfort, described as epigastric pain or burning, is common with therapeutic doses, and was reported in 38% of patients in one study (Gupta, 1977).
    B) TASTE SENSE ALTERED
    1) WITH THERAPEUTIC USE
    a) Unpleasant or metallic tastes are reported by 15% to 19% of patients taking therapeutic doses (Prod Info TRECATOR(R) oral tablets, 2005; Gupta, 1977; Devadatta et al, 1970) .

Hepatic

    3.9.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Increased liver enzyme levels have been reported in patients as an adverse effect.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Liver function abnormalities have been reported in patients taking therapeutic doses of ethionamide (Prod Info TRECATOR(R) oral tablets, 2005; de Carsalade et al, 1997; See et al, 1986; Pattyn et al, 1984) . Abnormalities have included increased serum transaminase concentrations (Simon et al, 1969; Anon, 1968; Kuntz et al, 1968), elevated serum bilirubin concentrations (Gupta et al, 1975; Kuntz et al, 1968), elevated alkaline phosphatase (Tala & Tevola, 1969; Kuntz et al, 1968), and hepatitis (with or without jaundice) (Prod Info TRECATOR(R) oral tablets, 2005; Anon, 1975).
    b) Many of these patients were taking several hepatotoxic drugs simultaneously, and it is difficult to determine with certainty which agent was responsible for the observed hepatotoxicity (Gryminski et al, 1970).
    c) In a series of 32 patients treated with ethionamide for tuberculosis or leprosy, 9 (28%) developed hepatotoxicity (de Carsalade et al, 1997).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Thrombocytopenia has been reported rarely during ethionamide therapy (Prod Info TRECATOR(R) oral tablets, 2005).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Various types of rashes, as well as alopecia, have been reported following therapeutic doses.
    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Various rashes have been reported with therapeutic use, including urticaria, punctate erythema, seborrheic dermatitis, acneiform eruptions, photosensitivity reactions, ichthyosis, and morbilliform purpura (Holdiness, 1985; Levantine & Almeyda, 1972) .
    B) ALOPECIA
    1) WITH THERAPEUTIC USE
    a) Alopecia has been reported with therapeutic use (Gupta, 1977; Simon et al, 1969) .

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCULOSKELETAL FINDING
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Algodystrophy (a painful local disturbance of growth) with an atypical shoulder-hand syndrome and pain in the knees, wrists, ankles, and interphalangeal deformities has been reported with therapeutic use of ethionamide (Lequesne & Moghtader, 1966). The patient improved when the ethionamide was discontinued.

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 68-year-old man developed severe hypoglycemia (coma with blood glucose less than 30 milligrams/deciliter) while being treated with streptomycin, isoniazid, and ethionamide for pulmonary tuberculosis (Cameron & Crompton, 1967). He was extremely thin and had a history of ethanol abuse, which may have contributed to the hypoglycemia.
    B) HYPOTHYROIDISM
    1) WITH THERAPEUTIC USE
    a) Hypothyroidism has been reported in 3 patients receiving ethionamide for treatment of pulmonary tuberculosis (Drucker et al, 1984; Moulding & Fraser, 1970). Signs and symptoms resolved and thyroid function tests returned to normal after the ethionamide was discontinued.
    C) DISORDER OF MENSTRUATION
    1) WITH THERAPEUTIC USE
    a) Menstrual irregularities have been reported with therapeutic use (Simon et al, 1969).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reactions including rash, photosensitivity, thrombocytopenia, and purpura have rarely been observed (Prod Info TRECATOR(R) oral tablets, 2005).
    b) CASE REPORT: A 35-year-old woman developed recurrent fevers, rash, nausea and vomiting, and twitching after receiving ethionamide and isoniazid (Carey, 1965). The reaction recurred when ethionamide alone was administered again. She underwent successful desensitization and continued therapy uneventfully.

Reproductive

    3.20.1) SUMMARY
    A) Use of the drug should be avoided during pregnancy or in women of childbearing potential unless the benefits outweigh its potential hazards.
    B) Developmental anomalies occured in women who received ethionamide during pregnancy; including congenital heart disease, spina bifida, spinal anomalies, Down's syndrome and possible hydrocephalus.
    3.20.2) TERATOGENICITY
    A) SUMMARY
    1) Use of the drug should be avoided during pregnancy or in women of childbearing potential unless the benefits outweigh its potential hazards (Prod Info Trecator-SC(R), ethionamide, 2000).
    B) CASE SERIES
    1) In a series of 16 children born to women who received ethionamide during pregnancy, 7 showed developmental anomalies (Potworowska et al, 1966).
    a) Two children were exposed only during the month prior to delivery; one of these had congenital heart disease and the other had spina bifida with multiple anomalies of the spine.
    b) Four patients were exposed during pregnancy. One of these children had Downs syndrome, short extremities, calcaneo-valgus deformity of the feet, and marked occult spina bifida.
    c) Four patients were exposed immediately prior to and during pregnancy. One of these children had Downs syndrome, poor psychomotor development and nystagmus; another had short extremities, a large head (possibly hydrocephalus), possible congenital heart disease and a hemangioma.
    C) ANIMAL STUDIES
    1) Studies in mice revealed no abnormalities when exposed to doses 10 times as high as those used in humans. With doses of 200 milligrams/kilogram administered on the 6th to 16th day in rats, abortion was common. With doses of 120 milligrams/kilogram in rats, congenital anomalies were common, most often involving the heart, roof of the palate and limbs (Bhatia & Raj, 1966).
    2) In rabbits, no teratogenic effects were found at doses of 15 milligrams/kilogram. At 100 milligrams/kilogram/day anomalies of the roof of the palate and limbs were observed. At 200 milligrams/kilogram/day abortions were common (Bhatia & Raj, 1966).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor liver enzyme levels after significant overdose.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor liver enzyme levels after significant overdose. Monitor serum electrolytes in patients with severe vomiting or diarrhea.

Methods

    A) CHROMATOGRAPHY
    1) A method for determining the concentration of ethionamide in biologic fluids using high-performance liquid chromatography (HPLC) with ultraviolet detection has been described (Malone et al, 1999; Peloquin & Gilman, 1991).
    2) High-performance liquid chromatographic-tandem mass spectrometric method (HPLC-MS-MS) has been used to determine ethionamide in human plasma, bronchoalveolar lavage fluid (BAL) and alveolar cells (AC). The detection limits for ethionamide were 0.05 microg/mL and 0.005 microg/mL for plasma and BAL supernatants and alveolar cells suspensions, respectively (Conte et al, 2001).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients demonstrating severe encephalopathy should be admitted.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All patients with overdose ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve.

Monitoring

    A) Monitor liver enzyme levels after significant overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Care is symptomatic and supportive.
    B) MONITORING OF PATIENT
    1) Monitor liver enzyme concentrations after significant overdose. Monitor electrolytes in patients with severe vomiting or diarrhea. Monitor for evidence of encephalopathy after significant overdose.
    C) PYRIDOXINE
    1) Case reports suggest that pyridoxine, nicotinamide and parenteral multiple vitamins may be useful in the treatment of ethionamide-induced encephalopathy (Sharma et al, 1979; Narang, 1972; Swash & Roberts, 1972).
    2) Doses of 100 to 150 mg/day of pyridoxine and 150 mg/day of nicotinamide have been reported (Sharma et al, 1979; Narang, 1972; Swash & Roberts, 1972).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Is unlikely to be useful in overdose because of the large volume of distribution.
    2) Only 2.1% of a 500 mg dose of ethionamide was recovered from dialysate (Malone et al, 1999).

Range Of Toxicity

Summary

    A) The toxic dose of ethionamide is not established. Adults have tolerated single oral doses of 90 mg/kg.

Therapeutic Dose

    7.2.1) ADULT
    A) TUBERCULOSIS
    1) The recommended initial oral dose in adults is 250 mg daily, gradually titrated to the optimal tolerated dose (Prod Info Trecator(R) oral film coated tablets, 2013).
    2) The usual adult oral dose is 15 to 20 mg/kg once daily (maximum 1 g daily); dose can be divided if patient shows poor gastrointestinal tolerance (Prod Info Trecator(R) oral film coated tablets, 2013).
    7.2.2) PEDIATRIC
    A) TUBERCULOSIS
    1) Ethionamide should not be used in pediatric patients younger than 12 years of age, except when the organisms have proven to be resistant to primary therapy and the disease is spreading, or when other life-threatening complications of tuberculosis are imminent (Prod Info Trecator(R) oral film coated tablets, 2013).
    2) The recommended pediatric oral dose is 10 to 20 mg/kg daily, divided between 2 or 3 doses and given after meals. An oral dose of 15 mg/kg every 24 hours is also recommended (Prod Info Trecator(R) oral film coated tablets, 2013).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Adults have tolerated single oral doses of 90 mg/kg once a week (Anon, 1975).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)MOUSE:
    a) 1000 mg/kg (RTECS, 2001)
    2) LD50- (ORAL)RAT:
    a) 1320 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Ethionamide is bacteriostatic against Mycobacterium tuberculosis at therapeutic concentrations; however, it may be bacteriocidal at higher concentrations (Prod Info Trecator(R) oral film coated tablets, 2013) . Though it is a second line agent, it has been recently shown to be very cost effective for multidrug resistant strains of Mycobacterium tuberculosis in low to middle-income countries (Suarez et al, 2002).

Physicochemical

Physical Characteristics

    A) Ethionamide is a yellow crystalline, nonhygroscopic compound with a faint to moderate sulfide odor and a melting point of 162 degrees C. It is soluble in methanol and ethanol and practically insoluble in water and ether (Prod Info Trecator(R) oral tablets, 2016).

Molecular Weight

    A) 166.24 (Prod Info Trecator(R) oral tablets, 2016)

References

General Bibliography

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    3) Anon: A controlled trial of daily and intermittent rifampicin plus ethambutol in the retreatment of patients with pulmonary tuberculosis: results up to 30 months. British Medical Research Council; Tubercle 1975; 56:179-189.
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    7) Carey VCI: Allergy to ethionamide. Tubercle 1965; 46:287-289.
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    14) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    15) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    16) Fox W, Robinson DK, & Tall R: A study of acute intolerance to ethionamide, including a comparison with prothionamide, and of the influence of a vitamin b-complex additive in prophylaxis. Tubercle Lond 1969; 50:125-143.
    17) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
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