Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/75
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Trecator (Tablet, Film Coated)
|
| dailymed-instance:dosage |
In the treatment of tuberculosis, a major cause of
the emergence of drug-resistant organisms, and thus treatment failure,
is patient nonadherence to prescribed treatment. Treatment failure
and drug-resistant organisms can be life-threatening and may result
in other serious health risks. It is, therefore, important that patients
adhere to the drug regimen for the full duration of treatment. Directly
observed therapy is recommended when patients are receiving treatment
for tuberculosis. Consultation with an expert in the treatment of
drug-resistant tuberculosis is advised for patients in whom drug-resistant
tuberculosis is suspected or likely. Ethionamide should be administered
with at least one, sometimes two, other drugs to which the organism
is known to be susceptible . Trecator is administered orally. The usual adult dose
is 15 to 20 mg/kg/day, administered once daily or, if patient
exhibits poor gastrointestinal tolerance, in divided doses, with a
maximum daily dosage of 1 gram. Trecator
tablets have been reformulated from a sugar-coated tablet to a film-coated
tablet. Patients should be monitored and have their dosage retitrated
when switching from the sugar-coated tablet to the film-coated tablet
. Therapy should be initiated at
a dose of 250 mg daily, with gradual titration to optimal doses as
tolerated by the patient. A regimen of 250 mg daily for 1 or 2 days,
followed by 250 mg twice daily for 1 or 2 days with a subsequent increase
to 1 gm in 3 or 4 divided doses has been reported.4,5 Thus far, there is insufficient evidence
to indicate the lowest effective dosage levels. Therefore, in order
to minimize the risk of resistance developing to the drug or to the
companion drug, the principle of giving the highest tolerated dose
(based on gastrointestinal intolerance) has been followed. In the
adult this would seem to be between 0.5 and 1.0 gm daily, with
an average of 0.75 gm daily. The optimum dosage
for pediatric patients has not been established. However, pediatric
dosages of 10 to 20 mg/kg p.o. daily in 2 or 3 divided doses
given after meals or 15 mg/kg/24 hrs as a single daily dose have
been recommended.1,2 As with
adults, ethionamide may be administered to pediatric patients once
daily. It should be noted that in patients with concomitant tuberculosis
and HIV infection, malabsorption syndrome may be present. Drug malabsorption
should be suspected in patients who adhere to therapy, but who fail
to respond appropriately. In such cases, consideration should be given
to therapeutic drug monitoring . The best times of administration are those which the individual
patient finds most suitable in order to avoid or minimize gastrointestinal
intolerance, which is usually at mealtimes. Every effort should be
made to encourage patients to persevere with treatment when gastrointestinal
side effects appear, since they may diminish in severity as treatment
proceeds. Concomitant administration of pyridoxine
is recommended. Duration of treatment should
be based on individual clinical response. In general, continue therapy
until bacteriological conversion has become permanent and maximal
clinical improvement has occurred.
|
| dailymed-instance:descripti... |
Trecator (ethionamide tablets, USP)
is used in the treatment of tuberculosis. The chemical name for ethionamide
is 2-ethylthioisonicotinamide with the following structural formula: Ethionamide is a yellow crystalline, nonhygroscopic
compound with a faint to moderate sulfide odor and a melting point
of 162��C. It is practically insoluble in water and ether, but
soluble in methanol and ethanol. It has a partition coefficient (octanol/water)
Log P value of 0.3699. Trecator tablets contain 250 mg of ethionamide.
The inactive ingredients present are croscarmellose sodium, FD&C
Yellow #6, magnesium stearate, microcrystalline cellulose, polyethylene
glycol, polyvinyl alcohol, povidone, silicon dioxide, talc, and titanium
dioxide.
|
| dailymed-instance:clinicalP... |
Absorption: Ethionamide is essentially completely absorbed following
oral administration and is not subjected to any appreciable first
pass metabolism. Ethionamide tablets may be administered without regard
to the timing of meals. The pharmacokinetic
parameters of ethionamide following single oral-dose administration
of 250 mg of Trecator film-coated tablets under fasted conditions
to 40 healthy adult volunteers are provided in Table 1. Trecator tablets have been reformulated from a
sugar-coated tablet to a film-coated tablet. The Cfor
the film-coated tablets (2.16��g/mL) was significantly higher
than that of sugar-coated tablets (1.48��g/mL) .<br/>Distribution: Ethionamide is rapidly and widely distributed into
body tissues and fluids following administration of a sugar-coated
tablet, with concentrations in plasma and various organs being approximately
equal. Significant concentrations are also present in cerebrospinal
fluid following administration of a sugar-coated tablet. Distribution
of ethionamide into the same body tissues and fluids, including cerebrospinal
fluid following administration of the film-coated tablet, has not
been studied, but is not expected to differ significantly from that
of the sugar-coated tablet. The drug is approximately 30% bound to
proteins. The mean (SD) apparent oral volume of distribution observed
in 40 healthy volunteers following a 250 mg oral dose of film-coated
tablets was 93.5 (19.2) L.<br/>Metabolism: Ethionamide is extensively metabolized to active
and inactive metabolites. Metabolism is presumed to occur in the liver
and thus far 6 metabolites have been isolated: 2-ethylisonicotinamide,
carbonyl-dihydropyridine, thiocarbonyl-dihydropyridine, S-oxocarbamoyl
dihydropyridine, 2-ethylthioiso-nicotinamide, and ethionamide sulphoxide.
The sulphoxide metabolite has been demonstrated to have antimicrobial
activity against Mycobacterium tuberculosis.<br/>Elimination: The mean (SD) half-life observed in 40 healthy volunteers
following a 250 mg oral dose of film-coated tablets was 1.92 (0.27)
hours. Less than 1% of the oral dose is excreted as ethionamide in
urine.<br/>Mechanism of Action: Ethionamide may be bacteriostatic or bactericidal
in action, depending on the concentration of the drug attained at
the site of infection and the susceptibility of the infecting organism.
The exact mechanism of action of ethionamide has not been fully elucidated,
but the drug appears to inhibit peptide synthesis in susceptible organisms.<br/>Microbiology:<br/>In Vitro Activity: Ethionamide exhibits bacteriostatic activity against
extracellular and intracellular Mycobacterium
tuberculosis organisms. The development of ethionamide resistant M. tuberculosis isolates can be obtained
by repeated subculturing in liquid or on solid media containing increasing
concentrations of ethionamide. Multi-drug resistant strains of M. tuberculosis may have acquired
resistance to both isoniazid and ethionamide. However, the majority
of M. tuberculosisisolates
that are resistant to one are usually susceptible to the other. There
is no evidence of cross-resistance between ethionamide and para-aminosalicylic
acid (PAS), streptomycin, or cycloserine. However, limited data suggest
that cross-resistance may exist between ethionamide and thiosemicarbazones
(i.e., thiacetazone) as well as isoniazid.<br/>In Vivo Activity: Ethionamide administered orally initially decreased
the number of culturable Mycobacterium
tuberculosis organisms from the lungs of H37Rv infected
mice. Drug resistance developed with continued ethionamide monotherapy,
but did not occur when mice received ethionamide in combination with
streptomycin or isoniazid.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Ethionamide is contraindicated in patients with severe
hepatic impairment and in patients who are hypersensitive to the drug.
|
| dailymed-instance:supply |
Trecator (ethionamide tablets, USP)
are supplied in bottles of 100 tablets as follows: 250 mg, orange film-coated tablet marked���W���on
one side and���4117���on reverse side, NDC 0008-4117-01. Store at controlled room temperature
20��to 25��C (68��to 77��F).
Dispense in a tight container.
|
| dailymed-instance:genericDr... | |
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:FD&C_Yellow_6,
dailymed-ingredient:croscarmellose_sodium,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:polyvinyl_alcohol,
dailymed-ingredient:povidone,
dailymed-ingredient:silicon_dioxide,
dailymed-ingredient:talc,
dailymed-ingredient:titanium_dioxide
|
| dailymed-instance:precautio... |
General: Ethionamide may potentiate the adverse effects of
the other antituberculous drugs administered concomitantly (see Drug Interactions). Ophthalmologic examinations (including ophthalmoscopy)
should be performed before and periodically during therapy with Trecator.<br/>Information For Patients: Patients should be advised to consult their physician
should blurred vision or any loss of vision, with or without eye pain,
occur during treatment. Excessive ethanol ingestion
should be avoided because a psychotic reaction has been reported.<br/>Laboratory Tests: Determination of serum transaminases (SGOT, SGPT)
should be made prior to initiation of therapy and should be monitored
monthly. If serum transaminases become elevated during therapy, ethionamide
and the companion antituberculosis drug or drugs may be discontinued
temporarily until the laboratory abnormalities have resolved. Ethionamide
and the companion antituberculosis medication(s) then should be reintroduced
sequentially to determine which drug (or drugs) is (are) responsible
for the hepatotoxicity. Blood glucose determinations
should be made prior to and periodically throughout therapy with Trecator.
Diabetic patients should be particularly alert for episodes of hypoglycemia. Periodic monitoring of thyroid function tests is recommended
as hypothyroidism, with or without goiter, has been reported with
ethionamide therapy.<br/>Drug Interactions: Trecator has been found to temporarily raise serum
concentrations of isoniazid. Trecator may potentiate the adverse effects
of other antituberculous drugs administered concomitantly. In particular,
convulsions have been reported when ethionamide is administered with
cycloserine and special care should be taken when the treatment regimen
includes both of these drugs. Excessive ethanol ingestion should be
avoided because a psychotic reaction has been reported.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility:<br/>Teratogenic Effects: Pregnancy Category C: Animal studies conducted with Trecator indicate that
the drug has teratogenic potential in rabbits and rats. The doses
used in these studies on a mg/kg basis were considerably in excess
of those recommended in humans. There are no adequate and well-controlled
studies in pregnant women. Because of these animal studies, however,
it must be recommended that Trecator be withheld from women who are
pregnant, or who are likely to become pregnant while under therapy,
unless the prescribing physician considers it to be an essential part
of the treatment.<br/>Labor and Delivery: The effect of Trecator on labor and delivery in pregnant
women is unknown.<br/>Nursing Mothers: Because no information is available on the excretion
of ethionamide in human milk, Trecator should be administered to nursing
mothers only if the benefits outweigh the risks. Newborns who are
breast-fed by mothers who are taking Trecator should be monitored
for adverse effects.<br/>Pediatric Use: Due to the fact that pulmonary tuberculosis resistant
to primary therapy is rarely found in neonates, infants, and children,
investigations have been limited in these age groups. At present,
the drug should not be used in pediatric patients under 12 years of
age except when the organisms are definitely resistant to primary
therapy and systemic dissemination of the disease, or other life-threatening
complications of tuberculosis, is judged to be imminent.
|
| dailymed-instance:overdosag... |
No specific information is available on the treatment
of overdosage with Trecator. If it should occur, standard procedures
to evacuate gastric contents and to support vital functions should
be employed.
|
| dailymed-instance:genericMe... |
ethionamide
|
| dailymed-instance:fullName |
Trecator (Tablet, Film Coated)
|
| dailymed-instance:adverseRe... |
Gastrointestinal: The most common side effects of
ethionamide are gastrointestinal disturbances including nausea, vomiting,
diarrhea, abdominal pain, excessive salivation, metallic taste, stomatitis,
anorexia and weight loss. Adverse gastrointestinal effects appear
to be dose related, with approximately 50% of patients unable to tolerate
1 gm as a single dose. Gastrointestinal effects may be minimized
by decreasing dosage, by changing the time of drug administration,
or by the concurrent administration of an antiemetic agent. Nervous System: Psychotic disturbances (including mental
depression), drowsiness, dizziness, restlessness, headache, and postural
hypotension have been reported with ethionamide. Rare reports of peripheral
neuritis, optic neuritis, diplopia, blurred vision, and a pellagra-like
syndrome also have been reported. Concurrent administration of pyridoxine
has been recommended to prevent or relieve neurotoxic effects. Hepatic: Transient increases in serum bilirubin, SGOT,
SGPT; Hepatitis (with or without jaundice). Other: Hypersensitivity reactions including rash, photosensitivity,
thrombocytopenia and purpura have been reported rarely. Hypoglycemia,
hypothyroidism, gynecomastia, impotence, and acne also have occurred.
The management of patients with diabetes mellitus may become more
difficult in those receiving ethionamide.
|
| dailymed-instance:warning |
The use of Trecator alone in the treatment of tuberculosis
results in rapid development of resistance. It is essential, therefore,
to give a suitable companion drug or drugs, the choice being based
on the results of susceptibility testing. However, therapy may be
initiated prior to receiving the results of susceptibility tests as
deemed appropriate by the physician. Ethionamide should be administered
with at least one, sometimes two, other drugs to which the organism
is known to be susceptible . Drugs which
have been used as companion agents are rifampin, ethambutol, pyrazinamide,
cycloserine, kanamycin, streptomycin, and isoniazid. The usual warnings,
precautions, and dosage regimens for these companion drugs should
be observed. Patient compliance is essential
to the success of the antituberculosis therapy and to prevent the
emergence of drug-resistant organisms. Therefore, patients should
adhere to the drug regimen for the full duration of treatment. It
is recommended that directly observed therapy be practiced when patients
are receiving antituberculous medication. Additional consultation
from experts in the treatment of drug-resistant tuberculosis is recommended
when patients develop drug-resistant organisms.
|
| dailymed-instance:indicatio... |
Trecator is primarily indicated for the treatment
of active tuberculosis in patients with M. tuberculosis resistant to isoniazid or rifampin,
or when there is intolerance on the part of the patient to other drugs.
Its use alone in the treatment of tuberculosis results in the rapid
development of resistance. It is essential, therefore, to give a suitable
companion drug or drugs, the choice being based on the results of
susceptibility tests. If the susceptibility tests indicate that the
patient's organism is resistant to one of the first-line antituberculosis
drugs (i.e., isoniazid or rifampin) yet susceptible to ethionamide,
ethionamide should be accompanied by at least one drug to which the M. tuberculosis isolate is known to
be susceptible.3 If the tuberculosis
is resistant to both isoniazid and rifampin, yet susceptible to ethionamide,
ethionamide should be accompanied by at least two other drugs to which
the M. tuberculosis isolate
is known to be susceptible.3 Patient nonadherence to prescribed treatment
can result in treatment failure and in the development of drug-resistant
tuberculosis, which can be life-threatening and lead to other serious
health risks. It is, therefore, essential that patients adhere to
the drug regimen for the full duration of treatment. Directly observed
therapy is recommended for all patients receiving treatment for tuberculosis.
Patients in whom drug-resistant M. tuberculosis organisms are isolated should be managed in consultation with an
expert in the treatment of drug-resistant tuberculosis.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Trecator
|