DIAMOX acetazolamide is an inhibitor of the enzyme carbonic anhydrase.
DIAMOX is a white to faintly yellowish white crystalline, odorless powder, weakly acidic, very slightly soluble in water and slightly soluble in alcohol. The chemical name for DIAMOX is N -(5-Sulfamoyl-1,3,4-thiadiazol-2-yl) acetamide. Its molecular weight is 222.24. Its chemical formula is C 4 H 6 N 4 O 3 S 2 .
DIAMOX SEQUELS are sustained-release capsules, for oral administration, each containing 500 mg of acetazolamide and the following inactive ingredients: Ethyl Vanillin, FD&C Blue No. 1, FD&C Yellow No. 6, Gelatin, Glycerin, Microcrystalline Cellulose, Methylparaben, Propylene Glycol, Propylparaben, Silicon Dioxide, and Sodium Lauryl Sulfate.
Clinical Pharmacology: DIAMOX is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (eg, some types of glaucoma), in the treatment of certain convulsive disorders (eg, epilepsy) and in the promotion of diuresis in instances of abnormal fluid retention (eg, cardiac edema).
DIAMOX is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.
DIAMOX is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme which 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 nonglaucomatous conditions. Evidence seems to indicate that DIAMOX has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (eg, epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of DIAMOX 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 3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus effected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.
DIAMOX acetazolamide SEQUELS sustained-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 SEQUELS permits a reduction in dosage frequency.
Plasma concentrations of acetazolamide peak between three to six hours after administration of DIAMOX SEQUELS, compared to one to four hours with tablets. Food does not affect the bioavailability of DIAMOX SEQUELS.
Placebo-controlled clinical trials have shown that prophylactic administration of DIAMOX 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 (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute mountain sickness (AMS). Pulmonary function (eg, minute ventilation, expired vital capacity, and peak flow) is greater in the DIAMOX treated group, both in subjects with AMS and asymptomatic subjects. The DIAMOX treated climbers also had less difficulty in sleeping.
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. DIAMOX 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.
Contraindications: 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 DIAMOX 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.
: 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. 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 DIAMOX acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported.
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 Patient
Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution 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, DIAMOX acetazolamide which may aggravate acidosis, should be used with caution.
Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and DIAMOX 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, ie, high altitude pulmonary edema (HAPE) or high altitude cerebral edema.
Caution is advised for patients receiving concomitant high-dose aspirin and DIAMOX acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported (see ).
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 DIAMOX 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of DIAMOX acetazolamide have not been conducted. In a bacterial mutagenicity assay, DIAMOX was 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 maximum recommended human dose of 1000 mg in a 50 kg individual.
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 DIAMOX, 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.
Pediatric Use
The safety and effectiveness of DIAMOX in pediatric patients have not been established.
Adverse Reactions: Adverse reactions, occurring most often early in therapy, include paresthesias, particularly a "tingling" feeling in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alteration and gastrointestinal disturbances such as nausea, vomiting and diarrhea; polyuria, and occasional instances of drowsiness and confusion.
Metabolic acidosis and electrolyte imbalance may occur.
Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuance of the medication.
Other occasional adverse reactions include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity and convulsions. Also see Precautions : Information for Patients for possible reactions common to sulfonamide derivatives. 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 (see ).
Overdosage: No data are available regarding DIAMOX overdosage in humans as no cases of acute poisoning with this drug have been reported. Animal data suggest that DIAMOX 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, DIAMOX may be dialyzable. This may be particularly important in the management of DIAMOX 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 DIAMOX acetazolamide SEQUELS sustained-release capsules, the desired control may be established by means of DIAMOX (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.
Dosage is 500 mg to 1000 mg daily, in divided doses using tablets or sustained-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: DIAMOX® acetazolamide SEQUELS®, 500 mg orange capsules printed with DIAMOX over D3 are supplied as follows:
NDC 0005-0753-23--Bottle of 100
Store at controlled room temperature 15°-30°C (59°-86°F).
Manufactured by:
LEDERLE PHARMACEUTICAL DIVISION
American Cyanamid Company
Pearl River, NY 10965
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