Label: ACETAZOLAMIDE capsule, extended release

Acetazolamide extended-release capsules are an inhibitor of the enzyme carbonic anhydrase.
Acetazolamide is a white to faintly yellowish white crystalline, odorless 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-Sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide and has the following chemical structure:

MW 222.25                          C4H6N403S2
Acetazolamide are extended-release capsules, for oral administration, each containing 500 mg of acetazolamide and the following inactive ingredients:
Microcrystalline cellulose, sodium lauryl sulfate and talc.

The ingredients in the capsule shell are D&C Red No. 28, D&C Yellow No. 10, FD&C Red No. 40, gelatin and titanium dioxide.

The ingredients in the imprinting ink are shellac, propylene glycol, potassium hydroxide and iron oxide black.

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 HCO3 ion, 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 pellets 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 extended-release capsules are 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 extended-release capsules, 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-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, 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

Special senses:  Hearing disturbances, tinnitus, transient  myopia 

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 extended-release capsules may  be dialyzable. This may be particularly important in the management of acetazolamide extended-release capsules overdosage  when complicated by the presence of renal  failure.

Glaucoma: 

The recommended dosage is 1 capsule (500 mg) two times a day. Usually 1 capsule is administered  in the morning and 1 capsule in the evening. It may be necessary to adjust the dose, but it has  usually been found that dosage in excess of 2 capsules (1 g) does not produce an increased effect. The  dosage should be adjusted with careful individual attention both to symptomatology and intraocular  tension. In all cases, continuous supervision by a physician is  advisable.

In those unusual instances where adequate control is not obtained by the twice-a-day administration  of acetazolamide extended-release capsules, the desired control may be established by means of acetazolamide (tablets  or parenteral). Use tablets or parenteral in accordance with the more frequent dosage  schedules recommended for these dosage forms, such as 250 mg every four hours, or an initial dose of 500  mg followed by 250 mg or 125 mg every four hours, depending on the case in  question.

Acute Mountain Sickness: Dosage is 500 mg to 1000 mg daily, in divided doses using tablets  or extended-release capsules as appropriate. In circumstances of rapid ascent, such as in rescue  or military operations, the higher dose level of 1000 mg is recommended. It is preferable to  initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer  as necessary to control  symptoms.

Acetazolamide extended-release capsules are available as: 

500 mg: Orange opaque cap and orange opaque body, size ‘00’ capsule having imprinting ‘A’ on cap and ‘247’ on body with black ink, filled with white to off-white pellets. 

NDC 46708-349-31                Bottle of 100 capsules

NDC 46708-349-91                Bottle of 1000 capsules

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

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

Manufactured by:

Alembic Pharmaceuticals Limited

(Formulation Division),

 Village Panelav, P. O. Tajpura,
Near Baska, Taluka-Halol,
Panchmahal 389350, Gujarat, India.

Revised: 08/2017

NDC 46708-349-31
acetaZOLAMDE
Extended-Release
Capsules
500 mg
Rx only
100 Capsules 
Alembic