Label: ACETAZOLAMIDE capsule, extended release

  • NDC Code(s): 62332-349-31, 62332-349-91
  • Packager: Alembic Pharmaceuticals Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated February 20, 2019

If you are a consumer or patient please visit this version.

  • DESCRIPTION

    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:
    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.




  • 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 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.

  • INDICATIONS  AND  USAGE

    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.

  • 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 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.

  • WARNINGS

    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.

  • PRECAUTIONS

    General

    Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness  and/or paresthesia. Increasing the dose often results in a decrease in diuresis. Under certain  circumstances, however, very large doses have been given in conjunction with other diuretics in order to  secure diuresis in complete refractory  failure.

    Information for Patients

    Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever,  rash (including erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis),  crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia,  leukopenia, pancytopenia, and agranulocytosis. Caution 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 extended-release capsules which may precipitate or aggravate acidosis should be used with caution. Gradual ascent  is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and acetazolamide extended-release capsules is  used, it should be noted that such use does not obviate the need for prompt descent if severe forms of  high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high altitude cerebral  edema.


    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 (see  WARNINGS).


    Both increases and decreases in blood glucose have been described in patients treated  with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance  or diabetes  mellitus.


    Acetazolamide treatment may cause electrolyte imbalances, including hyponatremia and  hypokalemia, as well as metabolic acidosis. Therefore, periodic monitoring of serum electrolytes is  recommended. Particular caution is recommended in patients with conditions that are associated with, or predispose  a patient to, electrolyte and acid/base imbalances, such as patients with impaired renal  function (including elderly patients; see PRECAUTIONS, Geriatric Use), patients with diabetes mellitus,  and patients with impaired alveolar  ventilation.


    Some adverse reactions to acetazolamide, such as drowsiness, fatigue, and myopia, may impair  the ability to drive and operate  machinery.

    Laboratory Tests

    To monitor for hematologic reactions common to all sulfonamides, it is recommended that a  baseline CBC and platelet count be obtained on patients prior to initiating acetazolamide extended-release capsules therapy and at  regular intervals during therapy. If significant changes occur, early discontinuance and institution  of appropriate therapy are important.  Periodic monitoring of serum electrolytes is  recommended.

    Drug Interactions

    Aspirin- See  WARNINGS 

     

    Acetazolamide extended-release capsules 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 extended-release capsules 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 extended-release capsules 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 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.

    Drug/laboratory test interactions

    Sulfonamides may give false negative or decreased values for urinary phenolsulfonphthalein  and phenol red elimination values for urinary protein, serum non-protein, and serum uric  acid. Acetazolamide may produce an increased level of crystals in the  urine.


    Acetazolamide interferes with the HPLC method of assay for theophylline. Interference with  the theophylline assay by acetazolamide depends on the solvent used in the extraction; acetazolamide  may not interfere with other assay methods for  theophylline.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Long-term studies in animals to evaluate the carcinogenic potential of acetazolamide extended-release capsules have not  been conducted. In a bacterial mutagenicity assay, acetazolamide extended-release capsules were not mutagenic when evaluated with  and without metabolic  activation.


    The drug had no effect on fertility when administered in the diet to male and female rats at a  daily intake of up to 4 times the recommended human dose of 1000 mg in a 50 kg  individual.

    Pregnancy: Teratogenic effects: Pregnancy Category C

    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 extended-release capsules, 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.

    Pediatric Use

    The safety and effectiveness of acetazolamide extended-release capsules in pediatric patients below the age of 12  years have not been established. Growth retardation has been reported in children receiving  long-term therapy, believed secondary to chronic  acidosis.

    Geriatric Use

    Metabolic acidosis, which can be severe, may occur in the elderly with reduced renal  function.


    In general, dose selection for an elderly patient should be cautious, usually starting at the low end  of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function,  and concomitant disease or other drug  therapy.

  • 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, 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

  • OVERDOSAGE

    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.

  • DOSAGE  AND  ADMINISTRATION

    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.

  • HOW SUPPLIED

    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 62332-349-31                Bottle of 100 capsules

    NDC 62332-349-91                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.


    You may also report side effects to Alembic Pharmaceuticals Limited at 1-866-210-9797.


    Manufactured by:

    Alembic Pharmaceuticals Limited

    (Formulation Division),

    Panelav 389350, Gujarat, India 


    Manufactured for:

    Alembic Pharmaceuticals, Inc.

    750 Route 202, Bridgewater, NJ 08807

    USA 


    Revised: 08/2017

  • PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 500 mg

    NDC 62332-349-31
    acetaZOLAMIDE
    Extended-Release
    Capsules
    500 mg
    Rx only
    100 Capsules 
    Alembic


    100 Capsules
  • INGREDIENTS AND APPEARANCE
    ACETAZOLAMIDE 
    acetazolamide capsule, extended release
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:62332-349
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ACETAZOLAMIDE (UNII: O3FX965V0I) (ACETAZOLAMIDE - UNII:O3FX965V0I) ACETAZOLAMIDE500 mg
    Inactive Ingredients
    Ingredient NameStrength
    MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)  
    SODIUM LAURYL SULFATE (UNII: 368GB5141J)  
    TALC (UNII: 7SEV7J4R1U)  
    D&C RED NO. 28 (UNII: 767IP0Y5NH)  
    D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
    FD&C RED NO. 40 (UNII: WZB9127XOA)  
    GELATIN, UNSPECIFIED (UNII: 2G86QN327L)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    SHELLAC (UNII: 46N107B71O)  
    PROPYLENE GLYCOL (UNII: 6DC9Q167V3)  
    POTASSIUM HYDROXIDE (UNII: WZH3C48M4T)  
    FERROSOFERRIC OXIDE (UNII: XM0M87F357)  
    Product Characteristics
    ColorORANGE (orange opaque cap and body) Scoreno score
    ShapeCAPSULESize24mm
    FlavorImprint Code A;247
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:62332-349-31100 in 1 BOTTLE; Type 0: Not a Combination Product02/20/2019
    2NDC:62332-349-911000 in 1 BOTTLE; Type 0: Not a Combination Product02/20/2019
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA21042302/20/2019
    Labeler - Alembic Pharmaceuticals Inc. (079288842)
    Establishment
    NameAddressID/FEIBusiness Operations
    Alembic Pharmaceuticals Limited650574671MANUFACTURE(62332-349)