DIAMOX® SEQUELS® (Acetazolamide Extended-Relea Capsules)
Rx only
DESCRIPTION
DIAMOX SEQUELS (Acetazolamide Extended-Relea Capsules) are an inhibitor of the enzyme carbonic anhydra.
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 and has the following chemical structure:
[structure]
C4H6N403S2
222.24
MW
DIAMOX SEQUELS are extended-relea capsules, for oral administration, each containing 500 mg of acetazolamide and the following inactive ingredients:
Microcrystalline cellulo, 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 D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40 aluminum lake, pharmaceutical glaze, propylene glycol and synthetic iron oxide.
CLINICAL PHARMACOLOGY
DIAMOX is a potent carbonic anhydra inhibitor, effective in the control of fluid cretion (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).
DIAMOX is not a mercurial diuretic. Rather, it is a non-bacteriostatic sulfonamide posssing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamid
es.
DIAMOX is an enzyme inhibitor that acts specifically on carbonic anhydra, 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 decreas the cretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cas of glaucoma and even in certain non-glaucomatous conditions. Evidence ems to indicate that DIAMOX has utility as an adjuvant in treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydra in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of DIAMOX 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 incread reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.
DIAMOX SEQUELS provide prolonged action to inhibit aqueous humor cretion for 18 to 24 hours after each do, 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 from three to six hours after administration of DIAMOX SEQUELS, compared to one to four hours with tablets. Food does not affect bioavailability of DIAMOX SEQUELS.
Placebo-controlled clinical trials have shown that prophylactic administration of DIAMOX at a do of 250 mg every eight to 12 hours (or a 500 mg controlled-relea capsule once daily) before and during rapid ascent to altitude results in fewer and/or less vere symptoms of acute mountain sickness (AMS) such as headache, naua, shortness of breath, dizziness, drowsiness, and fatigue. Pulmonary function (e.g., 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.
INDICATIONS AND USAGE
For adjunctive treatment of: chronic simple (open-angle) glaucoma, condary glaucoma, and preop
eratively 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 despite gradual ascent.泉州安全教育平台
爪开头的成语
CONTRAINDICATIONS
Hypernsitivity to acetazolamide or any excipients in the formulation. Since acetazolamide is a sulfonamide derivative, cross nsitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible.
Acetazolamide therapy is contraindicated in situations in which sodium and/or potassium blood rum levels are depresd, in cas of marked kidney and liver dia or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It is contraindicated in patients with cirrhosis becau of the risk of development of hepatic encephalopathy.
Long-term administration of DIAMOX is contraindicated in patients with chronic non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worning glaucoma is masked by lowered intraocular pressure.
WARNINGS
Fatalities have occurred, although rarely, due to vere 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 hypernsitivity or other rious reactions occur, discontinue u of this drug.
第十人理论Caution is advid for patients receiving concomitant high-do aspirin and DIAMOX, as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported.
PRECAUTIONS
General
Increasing the do does not increa the diuresis and may increa the incidence of drowsiness and/or paresthesia. Increasing the do often results in a decrea in diuresis. Under certain circumstances, however, very large dos have been given in conjunction with other diuretics in order to cure diuresis in complete refractory failure.
Information for Patients
Adver 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 advid for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.
In patients with pulmonary obstruction or emphyma where alveolar ventilation may be impaired, DIAMOX which may precipitate or aggravate acidosis should be ud with caution. Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and DIAMOX is ud, it should be noted that such u does not obviate the need for prompt descent if vere forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high altitude cerebral edema.
Caution is advid for patients receiving concomitant high-do aspirin and DIAMOX, as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported (e WARNINGS).
Both increas and decreas in blood gluco have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired gluco tolerance or diabetes mellitus.
Acetazolamide treatment may cau electrolyte imbalances, including hyponatremia and hypokalemia, as well as metabolic acidosis. Therefore, periodic monitoring of rum electrolytes is recommended. Particular caution is recommended in patients with conditions that are associated with, or predispo a patient to, electrolyte and acid/ba imbalances, such as patients with impaired renal function (including elderly patients; e PRECAUTIONS, Geriatric U), patients with diabetes mellitus, and patients with impaired alveolar ventilation.
Some adver reactions to acetazolamide, such as drowsiness, fatigue, and myopia, may impair the ability to drive and operate machinery.生鱼汤
Laboratory Tests
To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baline 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 rum electrolytes is recommended.
Drug Interactions
Aspirin- See WARNINGS
DIAMOX modifies phenytoin metabolism with incread rum levels of phenytoin. This may increa or enhance the occurrence of osteomalacia in some patients receiving chronic phenytoin therapy. Caution is advid in patients receiving chronic concomitant therapy. By decreasing the
gastrointestinal absorption of primidone, DIAMOX may decrea rum concentrations of primidone and its metabolites, with a conquent possible decrea in anticonvulsant effect. Caution is advid when beginning, discontinuing, or changing the do of DIAMOX in patients receiving primidone.
Becau of possible additive effects with other carbonic anhydra inhibitors, concomitant u is not advisable.
Acetazolamide may increa the effects of other folic acid antagonists.
Acetazolamide decreas 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 antiptic effect of methenamine.
Acetazolamide increas lithium excretion and the lithium may be decread.
Acetazolamide and sodium bicarbonate ud concurrently increas the risk of renal calculus formation.
Acetazolamide may elevate cyclosporine levels.
Drug/laboratory test interactions
Sulfonamides may give fal negative or decread values for urinary phenolsulfonphthalein and phenol red elimination values for urinary protein, rum non-protein, and rum uric acid. Acetazolamide may produce an incread 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 ud 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 DIAMOX have not been condu
cted. 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 recommended human do 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 ud in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
Becau of the potential for rious adver 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. Acetazolamide should only be ud by nursing women if the potential benefit justifies the potential risk to the child.
Pediatric U
The safety and effectiveness of DIAMOX SEQUELS 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 condary to chronic acidosis.
Geriatric U
Metabolic acidosis, which can be vere, may occur in the elderly with reduced renal function.
In general, do lection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decread hepatic, renal, or cardiac function, and concomitant dia or other drug therapy.
ADVERSE REACTIONS
Body as a whole: Headache, malai, fatigue, fever, pain at injection site, flushing, growth retardation in children, flaccid paralysis, anaphylaxis.
Digestive: Gastrointestinal disturbances such as naua, 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,喝浓茶可以解酒吗
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, photonsitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis
Special ns: Hearing disturbances, tinnitus, transient myopia
Urogenital: Crystalluria, incread 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, DIAMOX may be dialyzable. This may be particularly important in the management of DIAMOX overdosage when complicated by the prence of renal failure.
DOSAGE AND ADMINISTRATION
Glaucoma:
The recommended dosage is 1 capsule (500 mg) two times a day. Usually 1 capsule is administere
d in the morning and 1 capsule in the evening. It may be necessary to adjust the do, but it has usually been found that dosage in excess of 2 capsules (1 g) does not produce an incread effect. The dosage should be adjusted with careful individual attention both to symptomatology and intraocular tension. In all cas, continuous supervision by a physician is advisable.
In tho unusual instances where adequate control is not obtained by the twice-a-day administration of DIAMOX SEQUELS, the desired control may be established by means of DIAMOX (tablets or parenteral). U tablets or parenteral in accordance with the more frequent dosage schedules recommended for the dosage forms, such as 250 mg every four hours, or an initial do of 500 mg followed by 250 mg or 125 mg every four hours, depending on the ca in question.
Acute Mountain Sickness: Dosage is 500 mg to 1000 mg daily, in divided dos using tablets or extended-relea capsules as appropriate. In circumstances of rapid ascent, such as in rescue or military operations, the higher do 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.
中孝介花海HOW SUPPLIED
DIAMOX® SEQUELS® (Acetazolamide Extended-Relea Capsules) are available as 500 mg: Orange opaque cap and orange opaque body filled with white to off-white pellets. Imprinted in black ink, Barr 699. Available in bottles of:
100
NDC
51285-754-02
Store at controlled room temperature 20° to 25°C (68° to 77°F).
DURAMED PHARMACEUTICALS, INC.
Subsidiary of BarrPharmaceuticals, Inc.
铁牛哥Pomona, New York 10970
杨阜
Revid NOVEMBER 2004
BR-754
