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