Label: ACETAZOLAMIDE capsule

Acetazolamide Extended-release Capsules are an inhibitor of the enzyme carbonic anhydrase.

Acetazolamide, USP is a white to faintly yellowish white, crystalline odorless powder, sparingly soluble in practically boiling water, slightly soluble in alcohol, very slightly soluble in water. The chemical name for acetazolamide is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl) acetamide and has the following chemical structure:

MW 222.25 C 4H 6N 4O 3S 2

Each acetazolamide extended-release capsule, USP intended for oral administration contains 500 mg of acetazolamide. In addition, each capsule contains the following inactive ingredients: gelatin, iron oxide yellow, microcrystalline cellulose, sodium lauryl sulfate, talc and titanium dioxide. Each capsule is printed with black pharmaceutical ink which contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, shellac and strong ammonia solution.

Meets USP Dissolution Test 3.

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 non-bacteriostatic 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 non-glaucomatous conditions. Evidence seems to indicate that acetazolamide has utility as an adjuvant in 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 3ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.

Acetazolamide extended-release capsules provide prolonged action to inhibit aqueous humor secretion for 18 to 24 hours after each dose, whereas tablets act for only eight to 12 hours. The prolonged continuous effect of acetazolamide permits a reduction in dosage frequency.

Plasma concentrations of acetazolamide peak from three to six hours after administration of acetazolamide extended-release capsules, compared to one to four hours with tablets. Food does not affect bioavailability of acetazolamide extended-release capsules.

Placebo-controlled clinical trials have shown that prophylactic administration of acetazolamide at a dose of 250 mg every eight to 12 hours (or a 500 mg controlled release capsule once daily) before and during rapid ascent to altitude results in fewer and/or less severe symptoms of acute mountain sickness (AMS) such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue. Pulmonary function (e.g., minute ventilation, expired vital capacity, and peak flow) is greater in the acetazolamide treated group, both in subjects with AMS and asymptomatic subjects. The acetazolamide treated climbers also had less difficulty in sleeping.

For adjunctive treatment of: 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 extended-release capsules are also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness despite gradual ascent.

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 non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, anaphylaxis, 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, metabolic acidosis, coma, and death have been reported.

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, thrombocytopenic purpura, melena.

Hepato-biliarydisorders:
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, paresthesia (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.

No specific antidote is known. Treatment should be symptomatic and supportive.

Electrolyte imbalance, development of an acidotic state, and central nervous system 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 Extended-release Capsules USP, 500 mg are white to off white pellets filled in size "00el" empty hard gelatin capsules with opaque yellow colored cap imprinted with "XYL" in black ink and opaque white colored body imprinted with "34" in black ink and are supplied as follows:
Unit dose packages of 30 (3 x 10) NDC 60687-578-21

Storage
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

PACKAGING INFORMATION
American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Zydus Pharmaceuticals (USA) Inc. as follows:
(500 mg / 30 UD) NDC 60687-578-21 packaged from NDC 70710-1591

Distributed by:
American Health Packaging
Columbus, OH 43217

8457821/1124

NDC 60687- 578-21

AcetaZOLAMIDE
EXTENDED-RELEASE Capsules, USP

500 mg

30 Capsules (3 x 10)                 Rx Only

Each Hard Gelatin Capsule Contains:
AcetaZOLAMIDE, USP........................................................... 500 mg

Usual Dosage: See full prescribing information.

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].

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

The drug product contained in this package is from
NDC # 70710-1591, Zydus Pharmaceuticals (USA) Inc.

Distributed by: American Health Packaging, Columbus, Ohio 43217

757821
0457821/1124

AcetaZOLAMIDE
EXTENDED-RELEASE
Capsule, USP   500 mg