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.

DOSAGE AND ADMINISTRATION Preparation and Storage of Parenteral Solution Each 500 mg vial containing acetazolamide 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° to 8°C (36° to 46°F), or 12 hours at room temperature 20° to 25°C (68° to 77°F). CONTAINS NO PRESERVATIVE. The direct intravenous route of administration is preferred. Intramuscular administration is not recommended. Glaucoma: Acetazolamide 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 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 1,000 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. 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 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. Drug-Induced Edema: Recommended dosage is 250 to 375 mg of acetazolamide 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 the inhibitory effect of the therapeutic agent. Interference with Laborato…

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, and anaphylaxis. 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.

CONTRAINDICATIONS Hypersensitivity to acetazolamide or any excipients in the formulation. Since acetazolamide is a sulfonamide derivative, cross sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible. 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.

Pregnancy: Teratogenic effects 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 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.

ADVERSE REACTIONS Body as a whole: Headache, malaise, fatigue, fever, pain at injection site, flushing, growth retardation in children, flaccid paralysis, anaphylaxis Digestive: Gastrointestinal disturbances such as nausea, vomiting, diarrhea Hematological/Lymphatic: Blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, thrombocytopenic purpura, melena Hepato-biliary disorders: Abnormal liver function, cholestatic jaundice, hepatic insufficiency, fulminant hepatic necrosis Metabolic/Nutritional: Metabolic acidosis, electrolyte imbalance, including hypokalemia, hyponatremia, osteomalacia with long-term phenytoin therapy, loss of appetite, taste alteration, hyper/hypoglycemia Nervous: Drowsiness, paraesthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion, convulsions, dizziness Skin: Allergic skin reactions including urticaria, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis Otologic : Hearing disturbances, tinnitus Eye Disorders: choroidal effusion, choroidal detachment, transient myopia. Transient myopia is the result of forward movement of the ciliary body leading to a narrowing of the angle. Urogenital: Crystalluria, increased risk of nephrolithiasis with long-term therapy, hematuria, glycosuria, renal failure, polyuria To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.