Acetazolamide Description

AcetaZOLAMIDE, 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 AcetaZOLAMIDE is N - (5-Sulfamoyl- 1,3,4-thiadiazol-2-y1)-acetamide and has the following structural formula:

Each tablet, for oral administration, contains 125 mg or 250 mg of AcetaZOLAMIDE and the following inactive ingredients: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium lauryl sulfate.

Acetazolamide 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.

Acetazolamide Contraindications

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.

Acetazolamide Side Effects

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, coma and death have been reported.

Acetazolamide 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 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. 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, ie, 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.

Carcinogenesis, Mutagenesis, 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 1000 mg in a 50 kg individual.

Pregnancy

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 reaction 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.

Pediatric Use

The safety and effectiveness of AcetaZOLAMIDE in children have not been established.

Acetazolamide Overdosage

No data are available regarding AcetaZOLAMIDE overdosage in humans as no cases of acute poisoning with this drug have been reported. Animal data suggest that AcetaZOLAMIDE is remarkably nontoxic. 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.

Acetazolamide 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. 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, ie, 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 ).