Label: ACETAZOLAMIDE injection, powder, lyophilized, for solution

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.

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 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 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.

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 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.

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

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.

Pediatric Use

The safety and effectiveness of acetazolamide in pediatric patients 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 of concomitant disease or other drug therapy.

Glaucoma

Acetazolamide for Injection 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 four 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 four 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 in 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 to 30 mg per kg in divided doses. Although some patients respond to a low dose, the optimum range appears to be from 375 to 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 for injection 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 for injection 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 to 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 for injection yields best diuretic results when given on alternate days, or for two days alternating with a day of rest.

Failures in therapy may be due to overdosage or too frequent dosage. The use of Acetazolamide for injection does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.

Drug-Induced Edema

Recommended dosage is 250 to 375 mg of Acetazolamide for injection once a day for one or two days, alternating with a day of rest.

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 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.