acetaZOLAMIDE 500 MG 12HR Extended Release Oral Capsule
WARNINGS
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, anaphylaxis, 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.
DRUG INTERACTIONS
Drug Interactions:
OVERDOSAGE
No specific antidote is known.
Treatment should be symptomatic and supportive.
Electrolyte imbalance, development of an acidotic state, and central nervous system 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.
DESCRIPTION
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 for acetazolamide is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide and has the following chemical structure: MW 222.24 C4H6N4O3S2 Each acetazolamide extended-release capsule intended for oral administration contains 500 mg of acetazolamide.
In addition, each capsule contains the following inactive ingredients: ammonio methacrylate copolymer dispersion type A and B, FD&C yellow #6, gelatin, microcrystalline cellulose, sodium lauryl sulfate, talc and titanium dioxide.
The capsule is printed with black pharmaceutical ink which contains black iron oxide as a coloring agent.
Acetazolamide structural formula
HOW SUPPLIED
Acetazolamide Extended-Release Capsules, 500 mg are white to off-white pellets filled in empty hard gelatin capsules with orange opaque cap imprinted with “EP” in black ink and white opaque body imprinted with “107” in black ink and are supplied as follows: Unit dose packages of 30 (3×10) NDC 68084-401-21 Storage: Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] FOR YOUR PROTECTION: Do not use if blister is torn or broken.
GERIATRIC USE
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.
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 extended-release capsules are also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness despite gradual ascent.
PEDIATRIC USE
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.
PREGNANCY
Pregnancy: Teratogenic Effects
NUSRING MOTHERS
Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from acetazolamide, 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.
INFORMATION FOR PATIENTS
Information for Patients: 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.
Caution 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, metabolic acidosis, coma, and death have been reported (see WARNINGS ).
Both increases and decreases in blood glucose 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 PRECAUTIONS, PRECAUTIONS , 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.
DOSAGE AND ADMINISTRATION
Glaucoma: The recommended dosage is 1 capsule (500 mg) two 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 the twice-a-day administration of acetazolamide extended-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 four hours, or an initial dose of 500 mg followed by 250 mg or 125 mg every four hours, depending on the case in question.
Acute Mountain Sickness: Dosage is 500 mg to 1000 mg daily, in divided doses using tablets or extended-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 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.