DRUGS & SUPPLEMENTS
How old is patient?
Ebutol (Ethambutol Hydrochloride) Ebutol (Ethambutol Hydrochloride) hydrochloride is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. The structural formula is:
Ebutol (Ethambutol Hydrochloride) 100 and 400 mg tablets contain the following inactive ingredients: Gelatin, Hydroxypropyl Methylcellulose, Magnesium Stearate, Sodium Lauryl Sulfate, Sorbitol, Stearic Acid, Sucrose, Titanium Dioxide and other ingredients.
Ebutol (Ethambutol Hydrochloride), following a single oral dose of 25 mg/kg of body weight, attains a peak of 2 to 5 mg/mL in serum 2 to 4 hours after administration. When the drug is administered daily for longer periods of time at this dose, serum levels are similar. The serum level of Ebutol (Ethambutol Hydrochloride) falls to undetectable levels by 24 hours after the last dose except in some patients with abnormal renal function. The intracellular concentrations of erythrocytes reach peak values approximately twice those of plasma and maintain this ratio throughout the 24 hours.
During the 24-hour period following oral administration of Ebutol (Ethambutol Hydrochloride) approximately 50 percent of the initial dose is excreted unchanged in the urine, while an additional 8 to 15 percent appears in the form of metabolites. The main path of metabolism appears to be an initial oxidation of the alcohol to an aldehydic intermediate, followed by conversion to a dicarboxylic acid. From 20 to 22 percent of the initial dose is excreted in the feces as unchanged drug. No drug accumulation has been observed with consecutive single daily doses of 25 mg/kg in patients with normal kidney function, although marked accumulation has been demonstrated in patients with renal insufficiency.
Ebutol (Ethambutol Hydrochloride) diffuses into actively growing mycobacterium cells such as tubercle bacilli. Ebutol (Ethambutol Hydrochloride) appears to inhibit the synthesis of one or more metabolites, thus causing impairment of cell metabolism, arrest of multiplication, and cell death. No cross resistance with other available antimycobacterial agents has been demonstrated.
Ebutol (Ethambutol Hydrochloride) has been shown to be effective against strains of Mycobacterium tuberculosis but does not seem to be active against fungi, viruses, or other bacteria. Mycobacterium tuberculosis strains previously unexposed to Ebutol (Ethambutol Hydrochloride) have been uniformly sensitive to concentrations of 8 or less mcg/mL, depending on the nature of the culture media. When Ebutol (Ethambutol Hydrochloride) has been used alone for treatment of tuberculosis, tubercle bacilli from these patients have developed resistance to Ebutol (Ethambutol Hydrochloride) (ethambutol hydrochloride) by in-vitro susceptibility tests; the development of resistance has been unpredictable and appears to occur in a step-like manner. No cross resistance between Ebutol (Ethambutol Hydrochloride) and other antituberculous drugs has been reported. Ebutol (Ethambutol Hydrochloride) has reduced the incidence of the emergence of mycobacterial resistance to isoniazid when both drugs have been used concurrently.
An agar diffusion microbiologic assay, based upon inhibition of Mycobacterium smegmatis (ATCC 607) may be used to determine concentrations of Ebutol (Ethambutol Hydrochloride) in serum and urine.
Toxicological studies in dogs on high prolonged doses produced evidence of myocardial damage and failure, and depigmentation of the tapetum lucidum of the eyes, the significance of which is not known. Degenerative changes in the central nervous system, apparently not dose-related, have also been noted in dogs receiving Ebutol (Ethambutol Hydrochloride) hydrochloride over a prolonged period.
In the rhesus monkey, neurological signs appeared after treatment with high doses given daily over a period of several months. These were correlated with specific serum levels of Ebutol (Ethambutol Hydrochloride) and with definite neuroanatomical changes in the central nervous system. Focal interstitial carditis was also noted in monkeys which received Ebutol (Ethambutol Hydrochloride) hydrochloride in high doses for a prolonged period.
Ebutol (Ethambutol Hydrochloride) is indicated for the treatment of pulmonary tuberculosis. It should not be used as the sole antituberculous drug, but should be used in conjunction with at least one other antituberculous drug. Selection of the companion drug should be based on clinical experience, considerations of comparative safety, and appropriate in-vitro susceptibility studies. In patients who have not received previous antituberculous therapy, ie, initial treatment, the most frequently used regimens have been the following:
Ebutol (Ethambutol Hydrochloride) plus isoniazid
Ebutol (Ethambutol Hydrochloride) plus isoniazid plus streptomycin.
In patients who have received previous antituberculous therapy, mycobacterial resistance to other drugs used in initial therapy is frequent. Consequently, in such retreatment patients, Ebutol (Ethambutol Hydrochloride) should be combined with at least one of the second line drugs not previously administered to the patient and to which bacterial susceptibility has been indicated by appropriate in-vitro studies. Antituberculous drugs used with Ebutol (Ethambutol Hydrochloride) have included cycloserine, ethionamide, pyrazinamide, viomycin and other drugs. Isoniazid, aminosalicylic acid, and streptomycin have also been used in multiple drug regimens. Alternating drug regimens have also been utilized.
Ebutol (Ethambutol Hydrochloride) is contraindicated in patients who are known to be hypersensitive to this drug. It is also contraindicated in patients with known optic neuritis unless clinical judgment determines that it may be used. Ebutol (Ethambutol Hydrochloride) is contraindicated in patients who are unable to appreciate and report visual side effects or changes in vision (e.g., young children, unconscious patients).
Ebutol (Ethambutol Hydrochloride) may produce decreases in visual acuity which appear to be due to optic neuritis. This effect may be related to dose and duration of treatment. This effect is generally reversible when administration of the drug is discontinued promptly. However, irreversible blindness has been reported. (See PRECAUTIONS and ADVERSE REACTIONS ).
Liver toxicities including fatalities have been reported. Baseline and periodic assessment of hepatic function should be performed.
Ebutol Ebutol (Ethambutol Hydrochloride) hydrochloride is not recommended for use in pediatric patients under thirteen years of age since safe conditions for use have not been established.
Patients with decreased renal function need the dosage reduced as determined by serum levels of Ebutol (Ethambutol Hydrochloride), since the main path of excretion of this drug is by the kidneys.
Because this drug may have adverse effects on vision, physical examination should include ophthalmoscopy, finger perimetry and testing of color discrimination. In patients with visual defects such as cataracts, recurrent inflammatory conditions of the eye, optic neuritis, and diabetic retinopathy, the evaluation of changes in visual acuity is more difficult, and care should be taken to be sure the variations in vision are not due to the underlying disease conditions. In such patients, consideration should be given to relationship between benefits expected and possible visual deterioration since evaluation of visual changes is difficult. (For recommended procedures, see next paragraphs under ADVERSE REACTIONS ).
As with any potent drug, baseline and periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, should be performed.
The results of a study of coadministration of Ebutol (Ethambutol Hydrochloride) (50mg/kg) with an aluminum hydroxide containing antacid to 13 patients with tuberculosis showed a reduction of mean serum concentrations and urinary excretion of Ebutol (Ethambutol Hydrochloride) of approximately 20% and 13%, respectively, suggesting that the oral absorption of Ebutol (Ethambutol Hydrochloride) may be reduced by these antacid products. It is recommended to avoid concurrent administration of Ebutol (Ethambutol Hydrochloride) with aluminum hydroxide containing antacids for at least 4 hours following Ebutol (Ethambutol Hydrochloride) administration.
Teratogenic Effects: Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. There are reports of ophthalmic abnormalities occurring in
infants born to women on antituberculous therapy that included Ebutol. Ebutol (Ethambutol Hydrochloride) should be used during pregnancy
only if the benefit justifies the potential risk to the fetus.
Ebutol (Ethambutol Hydrochloride) has been shown to be teratogenic in pregnant mice and rabbits when given in high doses. When pregnant mice or
rabbits were treated with high doses of Ebutol (Ethambutol Hydrochloride) hydrochloride, fetal mortality was slightly but not significantly (P>0.05) increased.
Female rats treated with Ebutol (Ethambutol Hydrochloride) hydrochloride displayed slight but insignificant (P>0.05) decreases in fertility and litter size.
In fetuses born of mice treated with high doses of Ebutol (Ethambutol Hydrochloride) during pregnancy, a low incidence of cleft palate, exencephaly
and abnormality of the vertebral column were observed. Minor abnormalities of the cervical vertebra were seen in the newborn of
rats treated with high doses of Ebutol (Ethambutol Hydrochloride) hydrochloride during pregnancy. Rabbits receiving high doses of Ebutol (Ethambutol Hydrochloride) during
pregnancy gave birth to two fetuses with monophthalmia, one with a shortened right forearm accompanied by bilateral wrist-joint
contracture and one with hare lip and cleft palate.
Ebutol (Ethambutol Hydrochloride) is excreted into breast milk. The use of Ebutol (Ethambutol Hydrochloride) should be considered only if the expected benefit to the mother outweighs the potential risk to the infant.
Ebutol (ethambutol hydrochloride) is not recommended for use in pediatric patients under thirteen years of age since safe conditions for use have not been established.
There are limited data on the use of ethambutol in the elderly. One study of 101 patients, 65 years and older, on multiple drug antituberculosis regimens included 94 patients on Ebutol (Ethambutol Hydrochloride). No differences in safety or tolerability were observed in these patients compared with that reported in adults in general. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Ebutol (Ethambutol Hydrochloride) may produce decreases in visual acuity, including irreversible blindness, which appear to be due to optic neuritis. Optic neuropathy including optic neuritis or retrobulbar neuritis occurring in association with Ebutol (Ethambutol Hydrochloride) therapy may be characterized by one or more of the following events: decreased visual acuity, scotoma, color blindness, and/or visual defect. These events have also been reported in the absence of a diagnosis of optic or retrobulbar neuritis.
Patients should be advised to report promptly to their physician any change of visual acuity.
The change in visual acuity may be unilateral or bilateral and hence each eye must be tested separately and both eyes tested together. Testing of visual acuity should be performed before beginning Ebutol (Ethambutol Hydrochloride) therapy and periodically during drug administration, except that it should be done monthly when a patient is on a dosage of more than 15 mg per kilogram per day. Snellen eye charts are recommended for testing of visual acuity. Studies have shown that there are definite fluctuations of one or two lines of the Snellen chart in the visual acuity of many tuberculous patients not receiving Ebutol (Ethambutol Hydrochloride).
The following table may be useful in interpreting possible changes in visual acuity attributable to Ebutol (Ethambutol Hydrochloride).
| Initial |
| Reading Indicating |
| Significant |
Number of Lines
| Decrease |
Number of Points
In general, changes in visual acuity less than those indicated under “Significant Number of Lines” and “Decrease Number of Points” may be due to chance variation, limitations of the testing method, or physiologic variability. Conversely, changes in visual acuity equaling or exceeding those under “Significant Number of Lines” and “Decrease Number of Points” indicate need for retesting and careful evaluation of the patient's visual status. If careful evaluation confirms the magnitude of visual change and fails to reveal another cause, Ebutol (Ethambutol Hydrochloride) should be discontinued and the patient reevaluated at frequent intervals. Progressive decreases in visual acuity during therapy must be considered to be due to Ebutol (Ethambutol Hydrochloride).
If corrective glasses are used prior to treatment, these must be worn during visual acuity testing. During 1 to 2 years of therapy, a refractive error may develop which must be corrected in order to obtain accurate test results. Testing the visual acuity through a pinhole eliminates refractive error. Patients developing visual abnormality during Ebutol (Ethambutol Hydrochloride) treatment may show subjective visual symptoms before, or simultaneously with, the demonstration of decreases in visual acuity, and all patients receiving Ebutol (Ethambutol Hydrochloride) should be questioned periodically about blurred vision and other subjective eye symptoms.
Recovery of visual acuity generally occurs over a period of weeks to months after the drug has been discontinued. Some patients have received Ebutol (Ethambutol Hydrochloride) (ethambutol hydrochloride) again after such recovery without recurrence of loss of visual acuity.
Other adverse reactions reported include: hypersensitivity, anaphylactic/anaphylactoid reaction, dermatitis, erythema multiforme, pruritus, and joint pain; anorexia, nausea, vomiting, gastrointestinal upset, and abdominal pain; fever, malaise, headache, and dizziness; mental confusion, disorientation, and possible hallucinations; thrombocytopenia, leucopenia, and neutropenia. Numbness and tingling of the extremities due to peripheral neuritis have been reported.
Elevated serum uric acid levels occur and precipitation of acute gout has been reported. Pulmonary infiltrates, with or without eosinophilia, also have been reported during Ebutol (Ethambutol Hydrochloride) therapy. Liver toxicities, including fatalities, have been reported (See WARNINGS. ) Since Ebutol (Ethambutol Hydrochloride) is recommended for therapy in conjunction with one or more other antituberculous drugs, these changes may be related to the concurrent therapy. Hypersensitivity syndrome consisting ot cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, pericarditis. Fever and lymphadenopathy may be present.
Ebutol should not be used alone, in initial treatment or in retreatment. Ebutol (Ethambutol Hydrochloride) should be administered on a once every 24-hour basis only. Absorption is not significantly altered by administration with food. Therapy, in general, should be continued until bacteriological conversion has become permanent and maximal clinical improvement has occurred.
Ebutol (Ethambutol Hydrochloride) is not recommended for use in pediatric patients under thirteen years of age since safe conditions for use have not been established.
In patients who have not received previous antituberculous therapy, administer Ebutol (Ethambutol Hydrochloride) 15 mg/kg (7 mg/ lb) of body weight, as a single oral dose once every 24 hours. In the more recent studies, isoniazid has been administered concurrently in a single, daily, oral dose.
In patients who have received previous antituberculous therapy, administer Ebutol (Ethambutol Hydrochloride) 25 mg/kg (11 mg/lb) of body weight, as a single oral dose once every 24 hours. Concurrently administer at least one other antituberculous drug to which the organisms have been demonstrated to be susceptible by appropriate in-vitro tests. Suitable drugs usually consist of those not previously used in the treatment of the patient. After 60 days of Ebutol (Ethambutol Hydrochloride) administration, decrease the dose to 15 mg/kg (7mg/ lb) of body weight, and administer as a single oral dose once every 24 hours.
During the period when a patient is on a daily dose of 25 mg/kg, monthly eye examinations are advised.
See Table for easy selection of proper weight-dose tablet(s).
|15 mg/kg (7 mg/lb) Schedule|
|Weight Range||Daily Dose|
|Under 85 lbs.||Under 37 kg||500|
|85 - 94.5||37 – 43||600|
|95 - 109.5||43 – 50||700|
|110 - 124.5||50 – 57||800|
|125 - 139.5||57 – 64||900|
|140 - 154.5||64 – 71||1000|
|155 - 169.5||71 – 79||1100|
|170 - 184.5||79 – 84||1200|
|185 - 199.5||84 – 90||1300|
|200 - 214.5||90 – 97||1400|
|215 and Over||Over 97||1500|
|25 mg/kg (11 mg/lb) Schedule|
|Under 85 lbs.||Under 38 kg||900|
|85 - 92.5||38 - 42||1000|
|93 - 101.5||42 - 45.5||1100|
|102 - 109.5||45.5 – 50||1200|
|110 - 118.5||50 – 54||.1300|
|119 - 128.5||54 – 58||1400|
|129 - 136.5||58 – 62||1500|
|137 - 146.5||62 – 67||1600|
|147 - 155.5||67 – 71||1700|
|156 - 164.5||71 – 75||1800|
|165 - 173.5||75 – 79||1900|
|174 - 182.5||79 – 83||2000|
|183 - 191.5||83 – 87||2100|
|192 - 199.5||87 – 91||2200|
|200 - 209.5||91 – 95||2300|
|210 - 218.5||95 – 99||2400|
|219 and Over||Over 99||2500|
NDC: 50090-0417-2 98 TABLET, FILM COATED in a BOTTLE
Ebutol (Isoniazid) is recommended for all forms of tuberculosis in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant antituberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculosis with Ebutol (Isoniazid), or any other medication, is inadequate therapy.
Ebutol (Isoniazid) is recommended as preventive therapy for the following groups, regardless of age. (Note: the criterion for a positive reaction to a skin test (in millimeters of induration) for each group is given in parenthesis):
Preventive therapy may be considered for HIV infected persons who are tuberculin-negative but belong to groups in which the prevalence of tuberculosis infection is high. Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy.
Additionally, in the absence of any of the above risk factors, persons under the age of 35 with a tuberculin skin test reaction of 10 mm or more are also appropriate candidates for preventive therapy if they are a member of any of the following high-incidence groups:
Children who are less than 4 years old are candidates for Ebutol (Isoniazid) preventive therapy if they have >10 mm induration from a PPD Mantoux tuberculin skin test.
Finally, persons under the age of 35 who a) have none of the above risk factors (1-6); b) belong to none of the high-incidence groups; and c) have a tuberculin skin test reaction of 15 mm or more, are appropriate candidates for preventive therapy.
The risk of hepatitis must be weighed against the risk of tuberculosis in positive tuberculin reactors over the age of 35. However, the use of Ebutol (Isoniazid) is recommended for those with the additional risk factors listed above (1-6) and on an individual basis in situations where there is likelihood of serious consequences to contacts who may become infected.
Ebutol (Isoniazid) is contraindicated in patients who develop severe hypersensitivity reactions, including drug-induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to Ebutol (Isoniazid) such as drug fever, chills, arthritis; and acute liver disease of any etiology.
See the boxed WARNING .
All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If Ebutol therapy must be reinstituted, the drug should be given only after symptoms have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent hypersensitivity reaction.
Use of Ebutol (Isoniazid) should be carefully monitored in the following:
Because there is a higher frequency of Ebutol (Isoniazid) associated hepatitis among certain patient groups, including Age > 35, daily users of alcohol, chronic liver disease, injection drug use and women belonging to minority groups, particularly in the post-partum period, transaminase measurements should be obtained prior to starting and monthly during preventative therapy, or more frequently as needed. If any of the values exceed three to five times the upper limit of normal, Ebutol (Isoniazid) should be temporarily discontinued and consideration given to restarting therapy.
Ebutol should not be administered with food. Studies have shown that the bioavailability of Ebutol (Isoniazid) is reduced significantly when administered with food. Tyramine- and histamine-containing foods should be avoided in patients receiving Ebutol (Isoniazid). Because Ebutol (Isoniazid) has some monoamine oxidase inhibiting activity, an interaction with tyramine-containing foods (cheese, red wine) may occur. Diamine oxidase may also be inhibited, causing exaggerated response (e.g., headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (e.g., skipjack, tuna, other tropical fish).
A report of severe acetaminophen toxicity was reported in a patient receiving Ebutol (Isoniazid). It is believed that the toxicity may have resulted from a previously unrecognized interaction between Ebutol (Isoniazid) and acetaminophen and a molecular basis for this interaction has been proposed. However, current evidence suggests that Ebutol (Isoniazid) does induce P-450IIE1, a mixed-function oxidase enzyme that appears to generate the toxic metabolites, in the liver. Furthermore it has been proposed that Ebutol (Isoniazid) resulted in induction of P-450IIE1 in the patients liver which, in turn, resulted in a greater proportion of the ingested acetaminophen being converted to the toxic metabolites. Studies have demonstrated that pretreatment with Ebutol (Isoniazid) potentiates acetaminophen hepatotoxicity in rats1,2.
Ebutol is known to slow the metabolism of carbamazepine and increase its serum levels. Carbamazepine levels should be determined prior to concurrent administration with Ebutol (Isoniazid), signs and symptoms of carbamazepine toxicity should be monitored closely, and appropriate dosage adjustment of the anticonvulsant should be made3.
Potential interaction of ketoconazole and Ebutol (Isoniazid) may exist. When ketoconazole is given in combination with Ebutol (Isoniazid) and rifampin the AUC of ketoconazole is decreased by as much as 88% after 5 months of concurrent Ebutol (Isoniazid) and rifampin therapy4.
Ebutol may increase serum levels of phenytoin. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made5,6.
A recent study has shown that concomitant administration of Ebutol (Isoniazid) and theophylline may cause elevated plasma levels of theophylline, and in some instances a slight decrease in the elimination of Ebutol (Isoniazid). Since the therapeutic range of theophylline is narrow, theophylline serum levels should be monitored closely, and appropriate dosage adjustments of theophylline should be made7.
A recent case study has shown a possible increase in the plasma level of valproate when co-administered with Ebutol. Plasma valproate concentration should be monitored when Ebutol (Isoniazid) and valproate are co-administered, and appropriate dosage adjustments of valproate should be made8.
Ebutol (Isoniazid) has been shown to induce pulmonary tumors in a number of strains of mice. Ebutol (Isoniazid) has not been shown to be carcinogenic in humans. (Note: a diagnosis of mesothelioma in a child with prenatal exposure to Ebutol (Isoniazid) and no other apparent risk factors has been reported). Ebutol (Isoniazid) has been found to be weakly mutagenic in strains TA 100 and TA 1535 of Salmonella typhimurium (Ames assay) without metabolic activation.
Ebutol has been shown to have an embryocidal effect in rats and rabbits when given orally during pregnancy. Ebutol (Isoniazid) was not teratogenic in reproduction studies in mice, rats and rabbits. There are no adequate and well-controlled studies in pregnant women. Ebutol (Isoniazid) should be used as a treatment for active tuberculosis during pregnancy because the benefit justifies the potential risk to the fetus. The benefit of preventive therapy also should be weighed against a possible risk to the fetus. Preventive therapy generally should be started after delivery to prevent putting the fetus at risk of exposure; the low levels of Ebutol (Isoniazid) in breast milk do not threaten the neonate. Since Ebutol (Isoniazid) is known to cross the placental barrier, neonates of Ebutol (Isoniazid) treated mothers should be carefully observed for any evidence of adverse affects.
Since Ebutol (Isoniazid) is known to cross the placental barrier, neonates of isoniazid-treated mothers should be carefully observed for any evidence of adverse effects.
The small concentrations of Ebutol (Isoniazid) in breast milk do not produce toxicity in the nursing newborn; therefore, breast feeding should not be discouraged. However, because levels of Ebutol (Isoniazid) are so low in breast milk, they can not be relied upon for prophylaxis or therapy of nursing infants.
The most frequent reactions are those affecting the nervous system and the liver.
Nervous System Reactions - Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics), and is usually preceded by paresthesias of the feet and hands. The incidence is higher in "slow inactivators".
Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment, and toxic psychosis.
Hepatic Reactions - See boxed WARNING. Elevated serum transaminase (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice, and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise, and weakness. Mild hepatic dysfunction, evidenced by mild and transient elevation of serum transaminase levels occurs in 10% to 20% of patients taking Ebutol (Isoniazid). This abnormality usually appears in the first 1 to 3 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal, and generally, there is no necessity to discontinue medication during the period of mild serum transaminase elevation. In occasional instances, progressive liver damage occurs, with accompanying symptoms. If the SGOT value exceeds three to five times the upper limit of normal, discontinuation of the Ebutol (Isoniazid) should be strongly considered. The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age.
Gastrointestinal Reactions - Nausea, vomiting, and epigastric distress.
Hematologic Reactions - Agranulocytosis; hemolytic, sideroblastic, or aplastic anemia, thrombocytopenia; and eosinophilia.
Hypersensitivity Reactions - Fever, skin eruptions (morbilliform, maculopapular, purpuric, or exfoliative), lymphadenopathy, and vasculitis.
Metabolic and Endocrine Reactions - Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis, and gynecomastia.
Miscellaneous Reactions - Rheumatic syndrome and systemic lupus erythematosus-like syndrome.
To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, and the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Ebutol overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision, and visual hallucinations (including bright colors and strange designs) are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe, intractable seizures. Severe metabolic acidosis, acetonuria, and hyperglycemia are typical laboratory findings.
Untreated or inadequately treated cases of gross Ebutol (Isoniazid) overdosage, 80 mg/kg - 150 mg/kg, can cause neurotoxicity6 and terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion.
Absorption of drugs from the GI tract may be decreased by giving activated charcoal. Gastric emptying should also be employed in the asymptomatic patient. Safeguard the patient"s airway when employing these procedures. Patients who acutely ingest > 80 mg/kg should be treated with intravenous pyridoxine on a gram per gram basis equal to the Ebutol dose. If an unknown amount of Ebutol (Isoniazid) is ingested, consider an initial dose of 5 grams of pyridoxine given over 30 to 60 minutes in adults, or 80 mg/kg of pyridoxine in children.
Ensure adequate ventilation, support cardiac output, and protect the airway while treating seizures and attempting to limit absorption. If the dose of Ebutol (Isoniazid) is known, the patient should be treated initially with a slow intravenous bolus of pyridoxine, over 3 to 5 minutes, on a gram per gram basis, equal to the Ebutol (Isoniazid) dose. If the quantity of Ebutol (Isoniazid) ingestion is unknown, then consider an initial intravenous bolus of pyridoxine of 5 grams in the adult or 80 mg/kg in the child. If seizures continue, the dosage of pyridoxine may be repeated. It would be rare that more than 10 grams of pyridoxine would need to be given. The maximum safe dose for pyridoxine in Ebutol (Isoniazid) intoxication is not known. If the patient does not respond to pyridoxine, diazepam may be administered. Phenytoin should be used cautiously, because Ebutol (Isoniazid) interferes with the metabolism of phenytoin.
Obtain blood samples for immediate determination of gases, electrolytes, BUN, glucose, etc.; type and cross-match blood in preparation for possible hemodialysis.
Patients with this degree of INH intoxication are likely to have hypoventilation. The administration of sodium bicarbonate under these circumstances can cause exacerbation of hypercarbia. Ventilation must be monitored carefully, by measuring blood carbon dioxide levels, and supported mechanically, if there is respiratory insufficiency.
Both peritoneal and hemodialysis have been used in the management of Ebutol (Isoniazid) overdosage. These procedures are probably not required if control of seizures and acidosis is achieved with pyridoxine, diazepam and bicarbonate.
Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, utilize meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration, pneumonitis, etc.
: NOTE: For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: (1) the recommendations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42; RR-4, 1993 and (2) Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149; 1359-1374, 1994.
For Treatment of Tuberculosis - Ebutol (Isoniazid) is used in conjunction with other effective anti-tuberculosis agents. Drug susceptibility testing should be performed on the organisms initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli become resistant, therapy must be changed to agents to which the bacilli are susceptible.
Usual Oral Dosage (depending on the regimen used):
15 mg/kg up to 900 mg day, two or three times/week
20-40 mg/kg up to 900 mg/day, two or three time/week
There are 3 regimen options for the initial treatment of tuberculosis in children and adults:
Option 1: Daily Ebutol (Isoniazid), rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of Ebutol (Isoniazid) and rifampin daily or 2-3 times weekly. Ethambutol or streptomycin should be added to the initial regimen until sensitivity to Ebutol (Isoniazid) and rifampin is demonstrated. The addition of a fourth drug is optional if the relative prevalence of isoniazid-resistant Mycobacterium tuberculosis isolates in the community is less than or equal to four percent.
Option 2: Daily Ebutol (Isoniazid), rifampin, pyrazinamide, and streptomycin or ethambutol for 2 weeks followed by twice weekly administration of the same drugs for 6 weeks, subsequently twice weekly Ebutol (Isoniazid) and rifampin for 16 weeks.
Option 3: Three times weekly with Ebutol (Isoniazid), rifampin, pyrazinamide, and ethambutol or streptomycin for 6 months.
*All regimens given twice weekly or 3 times weekly should be administered by directly observed therapy.
The above treatment guidelines apply only when the disease is caused by organisms that are susceptible to the standard antituberculous agents. Because of the impact of resistance to Ebutol (Isoniazid) and rifampin on the response to therapy, it is essential that physicians initiating therapy for tuberculosis be familiar with the prevalence of drug resistance in their communities. It is suggested that ethambutol not be used in children whose visual acuity cannot be monitored.
The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness. For this reason, therapeutic decisions for the impaired host must be individualized. Since patients co-infected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of MDRTB.
The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease. Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective. Because of the insufficient data, miliary tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 months therapy.
Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative inaccessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings.
The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Pott's Disease. Corticosteriods have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.
The options listed above must be adjusted for the pregnant patient. Streptomycin interferes with in utero development of the ear and may cause congenital deafness. Routine use of pyrazinamide is also not recommended in pregnancy because of inadequate teratogenicity data. The initial treatment regimen should consist of Ebutol and rifampin. Ethambutol should be included unless primary Ebutol (Isoniazid) resistance is unlikely (isoniazid resistance rate documented to be less than 4%).
Multiple-drug resistant tuberculosis (i.e., resistance to at least Ebutol (Isoniazid) and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended.
A major cause of drug-resistant tuberculosis is patient non-compliance with treatment. The use of DOT can help assure patient compliance with drug therapy. DOT is the observation of the patient by a health care provider or other responsible person as the patient ingests anti-tuberculosis medications. DOT can be achieved with daily, twice weekly or thrice weekly regimens, and is recommended for all patients.
Before Ebutol (Isoniazid) preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Appropriate evaluations should be performed if Extra pulmonary tuberculosis is suspected.
Adults over 30 Kg: 300 mg per day in a single dose.
Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose. In situations where adherence with daily preventative therapy cannot be assured, 20-30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of administration8.
Continuous administration of Ebutol (Isoniazid) for a sufficient period is an essential part of the regimen because relapse rates are higher if chemotherapy is stopped prematurely. In the treatment of tuberculosis, resistant organisms may multiply and the emergence of resistant organisms during the treatment may necessitate a change in the regimen.
For following patient compliance: the Potts-Cozart test9, a simple colorimetric6 method of checking for Ebutol (Isoniazid) in the urine, is a useful tool for assuring patient compliance, which is essential for effective tuberculosis control. Additionally, Ebutol (Isoniazid) test strips are also available to check patient compliance.
Concomitant administration of pyridoxine (B6) is recommended in the malnourished and in those predisposed to neuropathy (e.g., alcoholics and diabetics).
Ebutol (Isoniazid) Tablets, USP 100 mg: White, Round Tablets; Debossed "West-ward" on one side and "260" on the Scored side.
Ebutol (Isoniazid) Tablets, USP 300 mg: White, Round Tablets; Debossed "West-ward 261" on one side and Scored on the other side.
Store at 20-25°C (68-77°F). Protect from light and moisture.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Adults and Children. Amer. J. Respir Crit Care Med.1994; 149: p 1359-1374.
Committee on Infectious Diseases; 23rd edition; p487.
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised February 2011
Ebutol (Isoniazid) 300mg Tablet
Depending on the reaction of the Ebutol after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ebutol not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Ebutol addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology