Ethambutol Information
Ethambutol (Ethambutol hydrochloride) Description
Ethambutol (Ethambutol hydrochloride) hydrochloride is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. Ethambutol (Ethambutol hydrochloride) hydrochloride is a white, crystalline powder. The structural formula is:
Each tablet, for oral administration, contains 100 mg or 400 mg Ethambutol (Ethambutol hydrochloride) hydrochloride.
In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, corn starch, magnesium stearate, povidone and talc. Film coating contains: ethyl cellulose, hypromellose, macrogol, propylene glycol, talc and titanium dioxide.
Ethambutol (Ethambutol hydrochloride) Clinical Pharmacology
Ethambutol (Ethambutol hydrochloride) hydrochloride tablets following a single oral dose of 25 mg/kg of body weight, attains a peak of 2 to 5 mcg/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 Ethambutol (Ethambutol hydrochloride) falls to undetectable levels by 24 hours after the last dose except in some patients with abnormal renal function. The intercellular 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 Ethambutol (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.
Ethambutol (Ethambutol hydrochloride) diffuses into actively growing Mycobacterium cells such as tubercle bacilli. Ethambutol (Ethambutol hydrochloride) hydrochloride tablets appear 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.
Ethambutol (Ethambutol hydrochloride) have been shown to be effective against strains of Mycobacterium tuberculosis but do not seem to be active against fungi, viruses, or other bacteria. Mycobacterium tuberculosis strains previously unexposed to Ethambutol (Ethambutol hydrochloride) hydrochloride have been uniformly sensitive to concentrations of 8 or less mcg/mL, depending on the nature of the culture media. When Ethambutol (Ethambutol hydrochloride) have been used alone for treatment of tuberculosis, tubercle bacilli from these patients have developed resistance to Ethambutol (Ethambutol hydrochloride) 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 Ethambutol (Ethambutol hydrochloride) hydrochloride tablets and other antituberculous drugs has been reported. Ethambutol (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 Ethambutol (Ethambutol hydrochloride) hydrochloride in serum and urines.
Ethambutol (Ethambutol hydrochloride) Animal Pharmacology
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 Ethambutol (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 Ethambutol (Ethambutol hydrochloride) and with definite neuroanatomical changes in the central nervous system. Focal interstitial carditis was also noted in monkeys which received Ethambutol (Ethambutol hydrochloride) hydrochloride in high doses for a prolonged period.
Ethambutol (Ethambutol hydrochloride) Indications And Usage
Ethambutol (Ethambutol hydrochloride) hydrochlorideis 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, i.e., initial treatment, the most freguently used regimens have been the following:
In patients who have received previous antituberculous therapy, mycobacterial resistance to other drugs used in initial therapy is frequent. Consequently, in such retreatment patients, Ethambutol (Ethambutol hydrochloride) hydrochloride tablets 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 Ethambutol (Ethambutol hydrochloride) hydrochloride tablets 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.
Ethambutol (Ethambutol hydrochloride) Contraindications
Ethambutol (Ethambutol hydrochloride) hydrochloride i contrainsdicated 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. Ethambutol (Ethambutol hydrochloride) hydrochloride tablets are contraindicated in patients who are unable to appreciate and report visual side ettects or changes in vision (e.g., young children, unconscious patients).
Ethambutol (Ethambutol hydrochloride) Warnings
Ethambutol (Ethambutol hydrochloride) hydrochloride tablets 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 and ).
Liver toxicities including fatalities have been reported (See ). Baseline and periodic assessment of hepatic function should be performed.
Ethambutol (Ethambutol hydrochloride) Precautions
Ethambutol (Ethambutol hydrochloride) hydrochloride tablets are not recommended for use in pediatric patients under 13 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 Ethambutol (Ethambutol hydrochloride) 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 ).
As with any potent drug, baseline and periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, should be performed.
Ethambutol (Ethambutol hydrochloride) Adverse Reactions
Ethambutol (Ethambutol hydrochloride) 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 Ethambutol (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 Ethambutol (Ethambutol hydrochloride) 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/kg/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 Ethambutol (Ethambutol hydrochloride) .
The following table may be useful in interpreting possible changes in visual acuity attributable to Ethambutol (Ethambutol hydrochloride) hydrochloride.
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 the need for retesting and careful evaluation of the patient's visual status. If careful evaluation confims the magnitude of visual change and fails to reveal another cause, Ethambutol (Ethambutol hydrochloride) hydrochloride tablets should be discontinued and the patient reevaluated at frequent intervals. Progressive decreases in visual acuity during therapy must be considered to be due to Ethambutol (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 retractive error. Patients developing visual abnormality during Ethambutol (Ethambutol hydrochloride) hydrochloride tablets treatment may show subjective visual symptoms before, or simultaneously with, the demonstration of decreases in visual acuity, and all patients receiving Ethambutol (Ethambutol hydrochloride) hydrochloride tablets 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 Ethambutol (Ethambutol hydrochloride) hydrochloride tablets again after such recovery without recurrence of loss of visual acuity. Other adverse reactions reported include: hypersensitivity, anaphylactic/anaphylactoid reaction, dermatitis, pruritus, and joint pain; anorexia, nausea, vomiting, gastrointestinal upset, and abdominal pain; fever, malaise, headache, and dizziness; mental confusion, disorientation, and possible hallucinations; thrombocytopenia, leukopenia, 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 Ethambutol (Ethambutol hydrochloride) hydrochloride tablets therapy. Liver toxicities, including fatalities, have been reported (See .) Since Ethambutol (Ethambutol hydrochloride) 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.
Ethambutol (Ethambutol hydrochloride) Dosage And Administration
Ethambutol (Ethambutol hydrochloride) hydrochloride should not be used alone, in initial treatment or in retreatment. Ethambutol (Ethambutol hydrochloride) hydrochloride tablets 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.
Ethambutol (Ethambutol hydrochloride) hydrochloride is not recommended for use in pediatric patients under 13 years of age since safe conditions for use have not been established.
Ethambutol (Ethambutol hydrochloride) How Supplied
Ethambutol (Ethambutol hydrochloride) Hydrochloride Tablets USP, 400 mg are available as white to off-white, round, biconvex, film-coated tablets debossed with 'L' and 'U' on either side of the breakline on one side and 'C32' on other side. They are supplied as follows:
NDC 68084-280-01 in unit dose packages of 100 (10x10).
Store at 20-25°C (68-77°F)[See USP Controlled Room Temperature]. Protect from light and moisture.
Manufactured byLupin Pharmaceuticals, Inc.Baltimore, Maryland 21202United States
Repackaged byAmerican Health PackagingColumbus, OH 43217
8228001/0609
Ethambutol (Ethambutol hydrochloride) Package/label Principal Display Panel
