Acetazolamide Information
Acetazolamide ()
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-2yl)-acetamide and has the following structural formula:
M.W. 222.24 CHNOS
Acetazolamide () is available for intravenous use, and is supplied as a sterile powder requiring reconstitution. Each vial contains Acetazolamide () sodium equivalent to 500 mg of Acetazolamide () . The bulk solution is adjusted to pH 9.6 using sodium hydroxide and, if necessary, hydrochloric acid prior to lyophilization.
Acetazolamide () 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 HCO ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus effected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.
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 () 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 () 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, coma and death have been reported.
Acetazolamide () Precautions
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.
Caution is advised for patients receiving concomitant high-dose aspirin and Acetazolamide () , as anorexia, tachypnea, lethargy, coma and death have been reported (see ).
Acetazolamide () Adverse Reactions
Adverse reactions, occurring most often early in therapy, include paresthesias, particularly a “tingling” feeling in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alteration and gastrointestinal disturbances such as nausea, vomiting and diarrhea; polyuria, and occasional instances of drowsiness and confusion.
Metabolic acidosis and electrolyte imbalance may occur.
Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuance of the medication.
Other occasional adverse reactions include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity and convulsions. Also see : for possible reactions common to sulfonamide derivatives. 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 (see ).
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 () Dosage And Administration
Each 500 mg vial containing sterile Acetazolamide () sodium 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 intravenous route of administration is preferred. Intramuscular administration is not recommended.
Acetazolamide () should be used as an adjunct to the usual therapy. The dosage employed in the treatment of 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 , 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.
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 children. Good results, however, have been seen in patients, both children 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 () 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.
For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg per 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 two 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.
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.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Acetazolamide () How Supplied
Acetazolamide () for Injection USP (lyophilized) powder.
NDC 55390-460-01
Store drug product at controlled room temperature
15°-30°C (59°-86°F).
Reconstituted solution should be stored in refrigerator at 2°- 8°C (36° - 46°F).
Use within 12 hours of reconstitution. Contains no preservative. Discard unused portion.
Acetazolamide () Vial Label
Acetazolamide () Carton
