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. Discard unused portion. The direct intravenous route of administration is preferred. Intramuscular administration is not recommended. Glaucoma: Acetazolamide for Injection, USP 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 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, USP 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, USP 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, USP 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, USP 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, USP 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 kidn …

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 for Injection 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 for Injection 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.

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 XGen Pharmaceuticals DJB, Inc. at 1-866-390-4411 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

DESCRIPTION Acetazolamide, an inhibitor of the enzyme carbonic anhydrase is a white to faintly yellowish white, crystalline powder, sparingly soluble in practically boiling water, very slightly soluble in water and slightly soluble in alcohol. The chemical name for acetazolamide is N -(5-Sulamoyl-1,3,4-thiadiazol-2-yl) acetamide and has the following chemical structure: Acetazolamide for injection, USP is available for intravenous use, and is supplied as a sterile, white or almost white to faintly yellowish white lyophilized powder or plug requiring reconstitution. Each vial contains an amount of acetazolamide sodium equivalent to 500 mg of acetazolamide, USP. The bulk solution is adjusted to pH 9.2 using sodium hydroxide and, if necessary, hydrochloric acid prior to lyophilization. Acetazolamide Chemical Structure

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.

HOW SUPPLIED Acetazolamide for Injection, USP (lyophilized) powder is supplied as follows: NDC Acetazolamide for Injection USP Packaging 23155-831-31 500 mg per vial 1 single-dose vial individually packed in a carton Store at 20° to 25°C (68° to 77°F) excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Reconstituted solution should be stored in refrigerator at 2° to 8°C (36° to 46°F). Use within 12 hours of reconstitution. Contains no preservative. Discard unused portion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Manufactured by: Emcure Pharmaceuticals Ltd., Sanand, Ahmedabad – 382110, India. Manufactured for: Avet Pharmaceuticals Inc. East Brunswick, NJ08816 1.866.901.DRUG (3784) PREMIERProRx ® is a registered trademark of Premier Healthcare Alliance, L.P., used under license. Revised: 02/2025 OR Manufactured by: OneSource Specialty Pharma Limited, Bengaluru, Karnataka - 561203, INDIA. Manufactured for: Avet Pharmaceuticals Inc. East Brunswick, NJ 08816 1.866.901.DRUG (3784) PREMIERProRx® is a registered trademark of Premier Healthcare Alliance, L.P., used under license Revised: 06/2025 premier-pro-logo