Overdose
No information provided.
Contraindications
ETHAMBUTOL HCl 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. ETHAMBUTOL HCl is contraindicated in patients who are unable to
appreciate and report visual side effects or changes in vision (e.g., young
children, unconscious patients).
Undesirable effects
MYAMBUTOL 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 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
MYAMBUTOL 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 MYAMBUTOL.
The following table may be useful in interpreting
possible changes in visual acuity attributable to MYAMBUTOL.
| Initial Snellen Reading |
Reading Indicating Significant Decrease |
Significant Number of Lines |
Decrease Number of Points |
| 20/13 |
20/25 |
3 |
12 |
| 20/15 |
20/25 |
2 |
10 |
| 20/20 |
20/30 |
2 |
10 |
| 20/25 |
20/40 |
2 |
15 |
| 20/30 |
20/50 |
2 |
20 |
| 20/40 |
20/70 |
2 |
30 |
| 20/50 |
20/70 |
1 |
20 |
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, MYAMBUTOL should be
discontinued and the patient reevaluated at frequent intervals. Progressive
decreases in visual acuity during therapy must be considered to be due to
MYAMBUTOL.
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 MYAMBUTOL treatment may show subjective visual symptoms
before, or simultaneously with, the demonstration of decreases in visual
acuity, and all patients receiving MYAMBUTOL 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 MYAMBUTOL (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, 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
MYAMBUTOL therapy. Liver toxicities, including fatalities, have been
reported. (See WARNINGS). Since
MYAMBUTOL 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 of 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.
Therapeutic indications
MYAMBUTOL 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:
MYAMBUTOL plus isoniazid
MYAMBUTOL 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, MYAMBUTOL 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 MYAMBUTOL
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.
Fertility, pregnancy and lactation
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 MYAMBUTOL.
MYAMBUTOL should be used during pregnancy only if the benefit justifies
the potential risk to the fetus.
MYAMBUTOL 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 ethambutol hydrochloride, fetal
mortality was slightly but not significantly (P > 0.05) increased. Female rats
treated with ethambutol hydrochloride displayed slight but insignificant
(P > 0.05) decreases in fertility and litter size. In fetuses born of mice
treated with high doses of MYAMBUTOL 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 ethambutol hydrochloride during pregnancy.
Rabbits receiving high doses of MYAMBUTOL 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.
Special warnings and precautions for use
WARNINGS
MYAMBUTOL 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
(see ADVERSE REACTIONS). Baseline and periodic assessment of hepatic
function should be performed.
PRECAUTIONS
MYAMBUTOL ethambutol 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 MYAMBUTOL, 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.
Pregnancy
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 MYAMBUTOL.
MYAMBUTOL should be used during pregnancy only if the benefit justifies
the potential risk to the fetus.
MYAMBUTOL 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 ethambutol hydrochloride, fetal
mortality was slightly but not significantly (P > 0.05) increased. Female rats
treated with ethambutol hydrochloride displayed slight but insignificant
(P > 0.05) decreases in fertility and litter size. In fetuses born of mice
treated with high doses of MYAMBUTOL 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 ethambutol hydrochloride during pregnancy.
Rabbits receiving high doses of MYAMBUTOL 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.
Nursing Mothers
MYAMBUTOL is excreted into breast milk. The use of
MYAMBUTOL should be considered only if the expected benefit to the mother
outweighs the potential risk to the infant.
Pediatric Use
MYAMBUTOL (ethambutol hydrochloride) is not
recommended for use in pediatric patients under thirteen years of age since
safe conditions for use have not been established.
Geriatric Use
There are limited data on the use of MYAMBUTOL in
the elderly. One study of 101 patients, 65 years and older, on multiple drug
antituberculosis regimens included 94 patients on MYAMBUTOL. 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.
Dosage (Posology) and method of administration
MYAMBUTOL should not be used alone, in initial
treatment or in retreatment. MYAMBUTOL 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.
MYAMBUTOL is not recommended for use in pediatric
patients under thirteen years of age since safe conditions for use have not
been established.
Initial Treatment: In patients who have not
received previous antituberculous therapy, administer MYAMBUTOL 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.
Retreatment: In patients who have received
previous antituberculous therapy, administer MYAMBUTOL 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 MYAMBUTOL 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).
Weight-Dose Table
| 15 mg/kg (7 mg/lb) Schedule |
| Weight Range Pounds |
Kilograms |
Dose In mg |
| 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 |
Interaction with other medicinal products and other forms of interaction
SIDE EFFECTS
MYAMBUTOL 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 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
MYAMBUTOL 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 MYAMBUTOL.
The following table may be useful in interpreting
possible changes in visual acuity attributable to MYAMBUTOL.
| Initial Snellen Reading |
Reading Indicating Significant Decrease |
Significant Number of Lines |
Decrease Number of Points |
| 20/13 |
20/25 |
3 |
12 |
| 20/15 |
20/25 |
2 |
10 |
| 20/20 |
20/30 |
2 |
10 |
| 20/25 |
20/40 |
2 |
15 |
| 20/30 |
20/50 |
2 |
20 |
| 20/40 |
20/70 |
2 |
30 |
| 20/50 |
20/70 |
1 |
20 |
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, MYAMBUTOL should be
discontinued and the patient reevaluated at frequent intervals. Progressive
decreases in visual acuity during therapy must be considered to be due to
MYAMBUTOL.
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 MYAMBUTOL treatment may show subjective visual symptoms
before, or simultaneously with, the demonstration of decreases in visual
acuity, and all patients receiving MYAMBUTOL 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 MYAMBUTOL (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, 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
MYAMBUTOL therapy. Liver toxicities, including fatalities, have been
reported. (See WARNINGS). Since
MYAMBUTOL 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 of 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.
DRUG INTERACTIONS
The results of a study of coadministration of MYAMBUTOL (50mg/kg) with an aluminum hydroxide containing antacid to 13 patients with
tuberculosis showed a reduction of mean serum concentrations and urinary
excretion of ethambutol of approximately 20% and 13%, respectively, suggesting
that the oral absorption of ethambutol may be reduced by these antacid
products. It is recommended to avoid concurrent administration of ethambutol
with aluminum hydroxide containing antacids for at least 4 hours following
ethambutol administration.