Acetazolamide (0086)
[ a-seat-a-zole'-a-mide ]
| Ingredients: |
Acetazolamide |
| Indications: |
Edema; Edema, drug- induced; Glaucoma, angle- closure; Glaucoma, open- angle; Glaucoma, secondary; Hypertension, ocular; Mountain sickness; Seizures, absence; Seizures, unlocalized; Edema, secondary to congestive heart failure |
| Pregnancy Category: |
C |
| FDA Approved: |
1953- 07- 01 |
| Classes: |
Carbonic anhydrase inhibitors; Orphan Drugs |
| HCFA Jcodes: |
J1120 |
| Brand Names: |
Acetadiazol
-
Mexico
;
Albox
-
Japan
;
Apo-Acetazolamide
-
Malaysia
;
Carbinib
-
Portugal
;
Cetamid
-
Philippines
;
Defiltran
-
Germany
;
Diamox
-
ASIA(Except
Bangladesh, Korea, Pakistan
), AUSTRALIA, EUROPE(Except
Bulgaria, Czech-republic, Germany, Greece, Hungary, Poland, Portugal, Slovenia, Turkey
), MIDDLEEAST, US; Argentina, Brazil, Canada, Chile, Ecuador, Mexico, Peru, South-africa, Venezuela
;
Diamox Sequels
-
US
;
Diamox Sustets
-
Colombia
;
Diluran
-
Czech-republic
;
Diural
-
Uruguay
;
Diuramid
-
Germany, Poland
;
Edemox
-
Spain
;
Genephamide
-
Peru
;
Glaucomed
-
Colombia
;
Glaucomide
-
New-zealand
;
Glaupax
-
Denmark, Ireland, Japan, Netherlands, Norway, Sweden, Switzerland, Thailand
;
Huma-Zolamide
-
Hungary
;
Ledamox
-
Japan
;
Lediamox
-
Portugal
;
Ledimox
-
Japan, Portugal
;
Stazol
-
Paraguay
;
|
| DEA schedules: |
(none)
|
| Cost of therapy: |
$0.08
(
Edema-Drug Induced ;
Generic Tablets (Alra) ;
250 mg ;
1 tablet/day ;
2 day supply
)
$0.40
(
Mountain Sickness ;
Generic Tablets (Alra) ;
250 mg ;
3 tablets/day ;
5 day supply
)
$2.40
(
Seizures ;
Generic Tablets (Alra) ;
250 mg ;
2 tablets/day ;
30 day supply
)
$4.80
(
Glaucoma ;
Generic Tablets (Alra) ;
250 mg ;
4 tablets/day ;
30 day supply
)
$152.28
(
Glaucoma ;
Diamox Sequels ;
500 mg ;
2 capsules/day ;
30 day supply
)
$22.50
(
Glaucoma (rapid IOP drop) ;
Generic Powder for Injection (Bedford) ;
500 mg/vial ;
500 mg ;
500 mg
)
|
Drug Form:Extended-Release Capsules
DESCRIPTION
|
| |
Diamox Sequels (acetazolamide extended- release capsules) are an inhibitor of the enzyme carbonic anhydrase.
Acetazolamide is a white to faintly yellowish white crystalline, odorless powder, weakly acidic, very slightly soluble in
water and slightly soluble in alcohol. The chemical name is N - (5- Sulfa- moyl- 1, 3, 4- thiadiazol- 2yl)- acetamide.
The molecular weight is 222.24 and the empirical formula is C4 H6 N4 03 S2 .
Diamox Sequels are extended- release capsules, for oral administration, each containing 500 mg of acetazolamide and the following
inactive ingredients: microcrystalline cellulose, sodium lauryl sulfate and talc.
The ingredients in the capsule shell are D&C red no. 28, D&C yellow no. 10, FD&C red no. 40, gelatin and titanium dioxide.
The ingredients in the imprinting ink are D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C blue no. 2
aluminum lake, FD&C red no. 40 aluminum lake, pharmaceutical glaze, propylene glycol and synthetic iron oxide.
|
CLINICAL PHARMACOLOGY
|
| |
Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion ( e.g., some types of glaucoma), in the treatment of certain convulsive disorders ( e.g., epilepsy) and in the promotion of diuresis in instances of abnormal fluid retention ( e.g., cardiac edema).
Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and
pharmacological activity distinctly different from the bacteriostatic sulfonamides.
Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible
reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action
of acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered
desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that acetazolamide
has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system ( e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from
central nervous system neurons. The diuretic effect of acetazolamide is due to its action in the kidney on the reversible
reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis is thus effected.
Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary
alkalinization.
Acetazolamide extended- release capsules provide prolonged action to inhibit aqueous humor secretion for 18- 24 hours after
each dose, whereas tablets act for only 8- 12 hours. The prolonged continuous effect of acetazolamide extended- release capsules
permit a reduction in dosage frequency.
Plasma concentrations of acetazolamide peak from 3- 6 hours after administration of acetazolamide extended- release capsules,
compared to 1- 4 hours with tablets. Food does not affect bioavailability of acetazolamide extended- release capsules.
Placebo- controlled clinical trials have shown that prophylactic administration of acetazolamide at a dose of 250 mg every
8- 12 hours (or a 500- mg controlled- release capsule once daily) before and during rapid ascent to altitude results in fewer
and/ or less severe symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute
mountain sickness (AMS). Pulmonary function ( e.g., minute ventilation, expired vital capacity, and peak flow) is greater in the acetazolamide- treated group, both in subjects
with AMS and asymptomatic subjects. The acetazolamide- treated climbers also had less difficulty in sleeping.
|
INDICATIONS AND USAGE
|
| |
For adjunctive treatment of: chronic simple (open- angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-
closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide is also indicated
for the prevention or amelioration of symptoms associated with acute mountain sickness despite gradual ascent.
|
CONTRAINDICATIONS
|
| |
Hypersensitivity to acetazolamide or any excipients in the formulation. Since acetazolamide is a sulfonamide derivative, cross
sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible.
Acetazolamide therapy is contraindicated in situations in which sodium and/ or potassium blood serum levels are depressed,
in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It
is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy.
Long- term administration of acetazolamide is contraindicated in patients with chronic noncongestive angle- closure glaucoma
since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.
|
WARNINGS
|
| |
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens- Johnson syndrome, toxic
epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitizations
may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or
other serious reactions occur, discontinue use of this drug.
Caution is advised for patients receiving concomitant high- dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy,
metabolic acidosis, coma and death have been reported.
|
PRECAUTIONS
|
| |
General
|
| |
Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/ or paresthesia. Increasing
the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in
conjunction with other diuretics in order to secure diuresis in complete refractory failure.
|
Information for the Patient
|
| |
Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme,
Stevens- Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic
purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such
reactions and the drug should be discontinued and appropriate therapy instituted.
In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, acetazolamide which may precipitate
or aggravate acidosis, should be used with caution.
Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and acetazolamide is used,
it should be noted that such use does not obviate the need for prompt descent if severe forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high- altitude cerebral edema.
Caution is advised for patients receiving concomitant high- dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy,
coma and death have been reported (see WARNINGS ).
|
Laboratory Tests
|
| |
To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count
be obtained on patients prior to initiating acetazolamide therapy and at regular intervals during therapy. If significant
changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes
is recommended.
|
Drug/Laboratory Test Interactions
|
| |
Sulfonamides may give false negative or decreased values for urinary phenolsulfonphthalein and phenol red elimination values
for urinary protein, serum non- protein, and serum uric acid.Acetazolamide may produce an increased level of crystals in the
urine.
Acetazolamide interferes with the HPLC method of assay for theophylline. Interference with the theophylline assay by acetazolamide
depends on the solvent used in the extraction; acetazolamide may not interfere with other assay methods for theophylline.
|
Carcinogenesis, Mutagenesis, and Impairment of Fertility
|
| |
Long- term studies in animals to evaluate the carcinogenic potential of acetazolamide have not been conducted. In a bacterial
mutagenicity assay, acetazolamide was not mutagenic when evaluated with and without metabolic activation. The drug had no
effect on fertility when administered in the diet to male and female rats at a daily intake of up to 4 times the recommended
human dose of 100 mg in a 50 kg individual.
|
Pregnancy, Teratogenic Effects, Pregnancy Category C
|
| |
Acetazolamide, administered orally or parenterally, has been shown to be teratogenic (defects of the limbs) in mice, rats,
hamsters and rabbits. There are no adequate and well- controlled studies in pregnant women. Acetazolamide should be used in
pregnancy only if the potential benefit justifies the potential risk to the fetus.
|
Nursing Mothers
|
| |
Because of the potential for serious adverse reactions in nursing infants from acetazolamide extended- release capsules, a
decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the
drug to the mother. Acetazolamide should only be used by nursing women if the potential benefit justifies the potential risk
to the child.
|
Pediatric Use
|
| |
The safety and effectiveness of acetazolamide extended- release capsules in pediatric patients below the age of 12 years have
not been established. Growth retardation has been reported in children receiving long- term therapy, believed secondary to
chronic acidosis.
|
Geriatric Use
|
| |
Metabolic acidosis, which can be severe, may occur in the elderly with reduced renal function.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range,
reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.
|
|
DRUG INTERACTIONS
|
| |
Aspirin: see WARNINGS .
Acetazolamide extended- release capsules modify phenytoin metabolism with increased serum levels of phenytoin. This may increase
or enhance the occurrence of osteomalacia in some patients receiving chronic phenytoin therapy. Caution is advised in patients
receiving chronic concomitant therapy. By decreasing the gastrointestinal absorption of primidone, Diamox may decrease serum
concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is
advised when beginning, discontinuing, or changing the dose of acetazolamide extended- release capsules in patients receiving
primidone.
Because of possible additive effects with other carbonic anhydrase inhibitors, concomitant use is not advisable.
Acetazolamide may increase the effects of other folic acid antagonists.
Acetazolamide decreases urinary excretion of amphetamine and may enhance the magnitude and duration of their effect.
Acetazolamide reduces urinary excretion of quinidine and may enhance its effect.
Acetazolamide may prevent the urinary antiseptic effect of methenamine.
Acetazolamide increases lithium excretion and the lithium may be decreased.
Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation.
Acetazolamide may elevate cyclosporine levels.
|
ADVERSE REACTIONS
|
| |
- Body as a Whole: Headache, malaise, fatigue, fever, pain at injection site, flushing, growth retardation in children, flaccid paralysis, anaphylaxis.
- Digestive: Gastrointestinal disturbances such as nausea, vomiting, diarrhea.
- Hematological/ Lymphatic: Blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenic purpura, melena.
- Hepato- Biliary Disorders: Abnormal liver function, cholestatic jaundice, hepatic insufficiency, fulminant hepatic necrosis.
- Metabolic/ Nutritional: Metabolic acidosis, electrolyte imbalance, including hypokalemia, hyponatremia, osteomalacia with long- term phenytoin therapy,
loss of appetite, taste alteration, hyper/ hypoglycemia.
- Nervous: Drowsiness, paresthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion,
convulsions dizziness.
- Skin: Allergic skin reactions including urticaria, photosensitivity, Stevens- Johnson syndrome, toxic epidermal necrolysis.
- Special Senses: Hearing disturbances, tinnitus, transient myopia.
- Urogenital: Crystalluria, increased risk of nephrolithiasis with long- term therapy, hematuria, glycosuria, renal failure polyuria.
|
OVERDOSAGE
|
| |
No specific antidote is known. Treatment should be symptomatic and supportive.
Electrolyte imbalance, development of an acidotic state, and central nervous effects might be expected to occur. Serum electrolyte
levels (particularly potassium) and blood pH levels should be monitored.
Supportive measures are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the
administration of bicarbonate.
Despite its high intraerythrocytic distribution and plasma protein binding properties, Acetazolamide may be dialyzable. This
may be particularly important in the management of acetazolamide overdosage when complicated by the presence of renal failure.
|
DOSAGE AND ADMINISTRATION
|
| |
Glaucoma
|
| |
The recommended dosage is 1 capsule (500 mg) 2 times a day. Usually 1 capsule is administered in the morning and 1 capsule
in the evening. It may be necessary to adjust the dose, but it has usually been found that dosage in excess of 2 capsules
(1 g) does not produce an increased effect. The dosage should be adjusted with careful individual attention both to symptomatology
and intraocular tension. In all cases, continuous supervision by a physician is advisable.
In those unusual instances where adequate control is not obtained by twice- a- day administration of acetazolamide sustained-
release capsules the desired control may be established by means of acetazolamide tablets or parenteral. Use tablets or parenteral
in accordance with the more frequent dosage schedules recommended for these dosage forms, such as 250 mg every 4 hours, or
an initial dose of 500 mg followed by 250 mg or 125 mg every 4 hours, depending on the case in question.
|
Acute Mountain Sickness
|
| |
Dosage is 500- 1000 mg daily, in divided doses using tablets or sustained- release capsules as appropriate. In circumstances
of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable
to initiate dosing 24- 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary
to control symptoms.
|
|
HOW SUPPLIED
|
| |
Diamox Sequels are available as 500- mg extended- release capsules with an orange opaque cap and an orange opaque body filled
with white to off- white pellets. Imprinted in black ink, “Barr 699.”
Storage: Store at controlled room temperature 20- 25°C (68- 77°F).
|
Drug Form:Tablets and Injection
DESCRIPTION
|
| |
Diamox, an inhibitor of the enzyme carbonic anhydrase is a white to faintly yellowish white crystalline, odorless powder,
weakly acidic, very slightly soluble in water and slightly soluble in alcohol. The chemical name for Diamox is N - (5- Sulfamoyl- 1, 3, 4- thiadiazol- 2- yl) acetamide.
Diamox has a molecular weight of 222.24 and the empirical formula is C4 H6 N4 O3 S2 .
Diamox is available as oral tablets containing 125 mg and 250 mg of acetazolamide, respectively, and the following inactive
ingredients: corn starch, dibasic calcium phosphate, magnesium stearate, povidone, and sodium starch glycolate.
Diamox is also available for IV use, and is supplied as a sterile powder requiring reconstitution. Each vial contains an amount
of acetazolamide sodium equivalent to 500 mg of acetazolamide. The bulk solution is adjusted to pH 9.2 using sodium hydroxide
and, if necessary, hydrochloric acid prior to lyophilization.
|
CLINICAL PHARMACOLOGY
|
| |
Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion ( e.g., some types of glaucoma), in the treatment of certain convulsive disorders ( e.g., epilepsy) and in the promotion of diuresis in instances of abnormal fluid retention ( e.g., cardiac edema).
Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and
pharmacological activity distinctly different from the bacteriostatic sulfonamides.
Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible
reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action
of acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered
desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that acetazolamide
has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system ( e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from
central nervous system neurons. The diuretic effect of acetazolamide is due to its action in the kidney on the reversible
reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected.
Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary
alkalinization.
Placebo- controlled clinical trials have shown that prophylactic administration of acetazolamide at a dose of 250 mg every
8- 12 hours (or a 500- mg controlled- release capsule once daily) before and during rapid ascent to altitude results in fewer
and/ or less severe symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute
mountain sickness (AMS). Pulmonary function ( e.g., minute ventilation, expired vital capacity, and peak flow) is greater in the acetazolamide treated group, both in subjects
with AMS and asymptomatic subjects. The acetazolamide treated climbers also had less difficulty in sleeping.
|
INDICATIONS AND USAGE
|
| |
For adjunctive treatment of: edema due to congestive heart failure; drug- induced edema; centrencephalic epilepsies (petit
mal, unlocalized seizures); chronic simple (open- angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-
closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide is also indicated
for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent
and in those who are very susceptible to acute mountain sickness despite gradual ascent.
|
CONTRAINDICATIONS
|
| |
Hypersensitivity to acetazolamide or any excipients in the formulation. Since acetazolamide is a sulfonamide derivative, cross
sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible.
Acetazolamide therapy is contraindicated in situations in which sodium and/ or potassium blood serum levels are depressed,
in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It
is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy.
Long- term administration of acetazolamide is contraindicated in patients with chronic noncongestive angle- closure glaucoma
since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.
|
WARNINGS
|
| |
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens- Johnson syndrome, toxic
epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, and anaphylaxis.
Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity
or other serious reactions occur, discontinue use of this drug.
Caution is advised for patients receiving concomitant high- dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy,
metabolic acidosis, coma, and death have been reported.
|
PRECAUTIONS
|
| |
General
|
| |
Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/ or paresthesia. Increasing
the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in
conjunction with other diuretics in order to secure diuresis in complete refractory failure.
|
Information for the Patient
|
| |
Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme,
Stevens- Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic
purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such
reactions and the drug should be discontinued and appropriate therapy instituted.
In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, acetazolamide which may precipitate
or aggravate acidosis, should be used with caution.
Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and acetazolamide is used,
it should be noted that such use does not obviate the need for prompt descent if severe forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high- altitude cerebral edema.
Caution is advised for patients receiving concomitant high- dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy,
coma and death have been reported (see WARNINGS ).
Both increases and decreases in blood glucose levels have been described in patients treated with acetazolamide. This should
be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus.
Acetazolamide treatment may cause electrolyte imbalances, including hyponatremia and hypokalemia, as well as metabolic acidosis.
Therefore, periodic monitoring of serum electrolytes is recommended. Particular caution is recommended in patients with conditions
that are associated with, or predispose a patient to, electrolyte and acid/ base imbalances, such as patients with impaired
renal function (including elderly patients; see Geriatric Use ), patients with diabetes mellitus, and patients with impaired alveolar ventilation.
Some adverse reactions to acetazolamide, such as drowsiness, fatigue, and myopia, may impair the ability to drive and operate
machinery.
|
Laboratory Tests
|
| |
To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count
be obtained on patients prior to initiating acetazolamide therapy and at regular intervals during therapy. If significant
changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes
is recommended.
|
Carcinogenesis, Mutagenesis, and Impairment of Fertility
|
| |
Long- term studies in animals to evaluate the carcinogenic potential of acetazolamide have not been conducted. In a bacterial
mutagenicity assay, acetazolamide was not mutagenic when evaluated with and without metabolic activation. The drug had no
effect on fertility when administered in the diet to male and female rats at a daily intake of up to 4 times the recommended
human dose of 100 mg in a 50- kg individual.
|
Pregnancy, Teratogenic Effects, Pregnancy Category C
|
| |
Acetazolamide, administered orally or parenterally, has been shown to be teratogenic (defects of the limbs) in mice, rats,
hamsters and rabbits. There are no adequate and well- controlled studies in pregnant women. Acetazolamide should be used in
pregnancy only if the potential benefit justifies the potential risk to the fetus.
|
Nursing Mothers
|
| |
Because of the potential for serious adverse reactions in nursing infants from acetazolamide extended- release capsules, a
decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the
drug to the mother. Acetazolamide should only be used by nursing women if the potential benefit justifies the potential risk
to the child.
|
Pediatric Use
|
| |
The safety and effectiveness of acetazolamide extended- release capsules in pediatric patients below the age of 12 years have
not been established.
Growth retardation has been reported in children receiving long- term therapy, believed secondary to chronic acidosis.
|
Geriatric Use
|
| |
Metabolic acidosis, which can be severe, may occur in the elderly with reduced renal function.
Clinical studies of acetazolamide did not include sufficient numbers of subjects aged 65 and over to determine whether they
respond differently from younger subjects. Other reported clinical experience has not identified differences in responses
between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting
at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and
concomitant disease or other drug therapy.
|
|
DRUG INTERACTIONS
|
| |
Aspirin: see WARNINGS .
Acetazolamide modifies phenytoin metabolism with increased serum levels of phenytoin. This may increase or enhance the occurrence
of osteomalacia in some patients receiving chronic phenytoin therapy. Caution is advised in patients receiving chronic concomitant
therapy.
By decreasing the gastrointestinal absorption of primidone, acetazolamide may decrease serum concentrations of primidone and
its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is advised when beginning, discontinuing,
or changing the dose of acetazolamide in patients receiving primidone.
Because of possible additive effects with other carbonic anhydrase inhibitors, concomitant use is not advisable.
Acetazolamide may increase the effects of other folic acid antagonists.
Acetazolamide may increase or decrease blood glucose levels. Consideration should be taken in patients being treated with
antidiabetic agents.
Acetazolamide decreases urinary excretion of amphetamine and may enhance the magnitude and duration of their effect.
Acetazolamide reduces urinary excretion of quinidine and may enhance its effect.
Acetazolamide may prevent the urinary antiseptic effect of methenamine.Acetazolamide increases lithium excretion and the lithium
may be decreased.
Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation.
Acetazolamide may elevate cyclosporine levels.
|
ADVERSE REACTIONS
|
| |
- Body as a Whole: Headache, malaise, fatigue, fever, pain at injection site, flushing, growth retardation in children, flaccid paralysis, anaphylaxis.
- Digestive: Gastrointestinal disturbances such as nausea, vomiting, diarrhea.
- Hematological/ Lymphatic: Blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenic purpura, melena.
- Hepato- Biliary Disorders: Abnormal liver function, cholestatic jaundice, hepatic insufficiency, fulminant hepatic necrosis.
- Metabolic/ Nutritional: Metabolic acidosis, electrolyte imbalance, including hypokalemia, hyponatremia, osteomalacia with long- term phenytoin therapy,
loss of appetite, taste alteration, hyper/ hypoglycemia.
- Nervous: Drowsiness, paresthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion,
convulsions dizziness.
- Skin: Allergic skin reactions including urticaria, photosensitivity, Stevens- Johnson syndrome, toxic epidermal necrolysis.
- Special Senses: Hearing disturbances, tinnitus, transient myopia.
- Urogenital: Crystalluria, increased risk of nephrolithiasis with long- term therapy, hematuria, glycosuria, renal failure polyuria.
|
OVERDOSAGE
|
| |
No specific antidote is known. Treatment should be symptomatic and supportive.
Electrolyte imbalance, development of an acidotic state, and central nervous effects might be expected to occur. Serum electrolyte
levels (particularly potassium) and blood pH levels should be monitored.
Supportive measures are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the
administration of bicarbonate.
Despite its high intraerythrocytic distribution and plasma protein binding properties, acetazolamide may be dialyzable. This
may be particularly important in the management of acetazolamide overdosage when complicated by the presence of renal failure.
|
DOSAGE AND ADMINISTRATION
|
| |
Preparation and Storage of Parenteral Solution
|
| |
Each 500- mg vial containing acetazolamide should be reconstituted with at least 5 ml of sterile water for injection prior
to use. Reconstituted solutions retain their physical and chemical properties for 3 days under refrigeration at 2- 8°C (36-
46°F), or 12 hours at room temperature 15- 30°C (59- 86°F). CONTAINS NO PRESERVATIVE. The direct IV route of administration
is preferred. Intramuscular administration is not recommended.
|
Glaucoma
|
| |
Acetazolamide should be used as an adjunct to the usual therapy. The dosage employed in the treatment of chronic simple (open- angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours, usually in divided doses for amounts over 250 mg. It has usually
been found that a dosage in excess of 1 g per 24 hours does not produce an increased effect. In all cases, the dosage should
be adjusted with careful individual attention both to symptomatology and ocular tension. Continuous supervision by a physician
is advisable.
In treatment of secondary glaucoma and in the preoperative treatment of some cases of acute congestive (closed- angle) glaucoma, the preferred dosage is 250 mg every 4 hours, although some cases have responded to 250 mg twice daily on short- term therapy.
In some acute cases, it may be more satisfactory to administer an initial dose of 500 mg followed by 125 or 250 mg every 4
hours depending on the individual case. Intravenous therapy may be used for rapid relief of ocular tension in acute cases.
A complementary effect has been noted when acetazolamide has been used in conjunction with miotics or mydriatics as the case
demanded.
|
Epilepsy
|
| |
It is not clearly known whether the beneficial effects observed in epilepsy are due to direct inhibition of carbonic anhydrase
in the central nervous system or whether they are due to the slight degree of acidosis produced by the divided dosage. The
best results to date have been seen in petit mal in pediatric patients. Good results, however, have been seen in patients,
both pediatric patients and adult, in other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns,
etc. The suggested total daily dose is 8- 30 mg per kg in divided doses.Although some patients respond to a low dose, the
optimum range appears to be from 375- 1000 mg daily. However, some investigators feel that daily doses in excess of 1 g do
not produce any better results than a 1 g dose. When acetazolamide is given in combination with other anticonvulsants, it
is suggested that the starting dose should be 250 mg once daily in addition to the existing medications. This can be increased
to levels as indicated above.
The change from other medications to acetazolamide should be gradual and in accordance with usual practice in epilepsy therapy.
|
Congestive Heart Failure
|
| |
For diuresis in congestive heart failure, the starting dose is usually 250- 375 mg once daily in the morning (5 mg/ kg). If,
after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney
recovery by skipping medication for a day. Acetazolamide yields best diuretic results when given on alternate days, or for
2 days alternating with a day of rest.
Failures in therapy may be due to overdosage or too frequent dosage. The use of acetazolamide does not eliminate the need
for other therapy such as digitalis, bed rest, and salt restriction.
|
Drug-Induced Edema
|
| |
Recommended dosage is 250- 375 mg of acetazolamide once a day for 1 or 2 days, alternating with a day of rest.
|
Acute Mountain Sickness
|
| |
Dosage is 500- 1000 mg daily, in divided doses using tablets or sustained- release capsules as appropriate. In circumstances
of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable
to initiate dosing 24- 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary
to control symptoms.
Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the
first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage
if it is to recover from the inhibitory effect of the therapeutic agent.
|
Interference with Laboratory Tests
|
| |
Sulfonamides may give false negative or decreased values for urinary phenolsulfonphthalein and phenol red elimination values
for urinary protein, serum non- protein and for serum uric acid. Acetazolamide may produce an increased level of crystals
in the urine.
Acetazolamide interferes with the HPLC method of assay for theophylline. Interference with the theophylline assay by acetazolamide
depends on the solvent used in the extraction; acetazolamide may not interfere with other assay methods for theophylline.
|
|
HOW SUPPLIED
|
| |
Diamox Tablets
|
| |
- 125 mg: Round, flat- faced, beveled, white tablets engraved with "Diamox" and "125" on one side and scored in half on the other side.
Engraved with "LL" on the right of the score and "D1" on the left
- 250 mg: Round, convex, white tablets engraved with “Diamox” and “250” on one side and scored in quarters on the other side. Engraved
with “LL” in the upper right quadrant and “D2” in the lower left quadrant.
Storage: Store at 20- 25°C (68- 77°F).
|
Diamox IV
|
| |
Sterile IV (lyophilized) powder.
Storage: Store at 20- 25°C (68- 77°F).
|
|
PRODUCT IDENTIFICATION
|
| |
Acetazolamide ,
tablet ,
250 mg
[ Watson Pharmaceuticals
]
Acetazolamide ,
tablet ,
250 mg
[ Watson Pharmaceuticals
]
Acetazolamide ,
tablet ,
250 mg
[ Watson Pharmaceuticals
]
Acetazolamide ,
capsule, extended release ,
500 mg
[ Wyeth-Ayerst Laboratories
]
Acetazolamide ,
tablet ,
250 mg
[ Taro Pharmaceuticals U.S.A. Inc
]
Acetazolamide ,
tablet ,
125 mg
[ United Research Laboratories/Mutual Pharmaceutical Company
]
Acetazolamide ,
tablet ,
125 mg
[ Taro Pharmaceuticals U.S.A. Inc
]
Acetazolamide ,
tablet ,
125 mg
[ United Research Laboratories/Mutual Pharmaceutical Company
]
|
PRODUCT LISTING - RATED THERAPEUTICALLY EQUIVALENT
|
| |
| powder for injection - injectable - 500 mg -
|
| 1.0 |
$22.50 |
GENERIC
Bedford Laboratories
|
55390046001 |
| tablet - oral - 125 mg -
|
| 100.0's |
$12.50 |
GENERIC
Taro Pharmaceuticals U.S.A. Inc
|
51672402201 |
| 100.0's |
$21.10 |
GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company
|
00677124801 |
| tablet - oral - 250 mg -
|
| 12.0's |
$5.24 |
GENERIC
Allscripts Healthcare Solutions
|
54569169700 |
| 30.0's |
$7.17 |
GENERIC
Heartland Healthcare Services
|
61392070030 |
| 30.0's |
$7.17 |
GENERIC
Heartland Healthcare Services
|
61392070039 |
| 30.0's |
$7.17 |
GENERIC
Heartland Healthcare Services
|
61392001763 |
| 30.0's |
$7.17 |
GENERIC
Heartland Healthcare Services
|
61392017639 |
| 30.0's |
$7.17 |
GENERIC
Heartland Healthcare Services
|
61392017630 |
| 30.0's |
$16.93 |
Diamox
Allscripts Healthcare Solutions
|
54569054100 |
| 31.0's |
$7.41 |
GENERIC
Heartland Healthcare Services
|
61392070031 |
| 31.0's |
$7.41 |
GENERIC
Heartland Healthcare Services
|
61392017631 |
| 32.0's |
$7.65 |
GENERIC
Heartland Healthcare Services
|
61392070032 |
| 45.0's |
$10.76 |
GENERIC
Heartland Healthcare Services
|
61392070045 |
| 60.0's |
$14.34 |
GENERIC
Heartland Healthcare Services
|
61392070060 |
| 60.0's |
$14.34 |
GENERIC
Heartland Healthcare Services
|
61392001766 |
| 60.0's |
$14.34 |
GENERIC
Heartland Healthcare Services
|
61392017660 |
| 60.0's |
$14.34 |
GENERIC
Heartland Healthcare Services
|
61392017665 |
| 90.0's |
$21.51 |
GENERIC
Heartland Healthcare Services
|
61392001769 |
| 90.0's |
$21.51 |
GENERIC
Heartland Healthcare Services
|
61392017690 |
| 90.0's |
$21.51 |
GENERIC
Heartland Healthcare Services
|
61392070090 |
| 100.0's |
$4.00 |
GENERIC
Alra Laboratories
|
51641015301 |
| 100.0's |
$5.94 |
GENERIC
Qualitest Pharmaceuticals Inc
|
00603207021 |
| 100.0's |
$14.98 |
GENERIC
Lannett Company Inc
|
00527105001 |
| 100.0's |
$22.50 |
GENERIC
Taro Pharmaceuticals U.S.A. Inc
|
51672402301 |
| 100.0's |
$28.00 |
GENERIC
Watson Pharmaceuticals
|
00591543001 |
| 100.0's |
$43.59 |
GENERIC
Allscripts Healthcare Solutions
|
54569169702 |
| 100.0's |
$56.44 |
Diamox
Wyeth- Ayerst Laboratories
|
00005446923 |
| 500.0's |
$119.50 |
GENERIC
Heartland Healthcare Services
|
61392070051 |
| 500.0's |
$240.00 |
GENERIC
Lannett Company Inc
|
00527105005 |
| 1000.0's |
$85.00 |
GENERIC
CMC- Consolidated Midland Corporation
|
00223003902 |
| 1000.0's |
$280.00 |
GENERIC
Lannett Company Inc
|
00527105010 |
| 2000.0's |
$478.00 |
GENERIC
Heartland Healthcare Services
|
61392070054 |
| 10000.0's |
$2390.00 |
GENERIC
Heartland Healthcare Services
|
61392070091 |
|
PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
|
| |
| capsule, extended release - oral - 500 mg -
|
| 100.0 |
$161.23 |
Diamox Sequels
Wyeth- Ayerst Laboratories
|
00005075323 |
| 100.0 |
$175.74 |
Diamox Sequels
Barr Laboratories Inc
|
51285075402 |
| powder - compounding - 100% -
|
| 25.0 gm |
$85.00 |
GENERIC
Medisca Inc
|
38779041025 |
| 100.0 gm |
$230.00 |
GENERIC
Medisca Inc
|
38779041010 |
| tablet - oral - 250 mg -
|
| 5.0's |
$1.74 |
GENERIC
Allscripts Healthcare Solutions
|
54569169701 |
| 12.0's |
$6.59 |
GENERIC
Physicians Total Care
|
54868119502 |
| 100.0's |
$41.83 |
GENERIC
Physicians Total Care
|
54868119501 |
|
|