Acetazolamide (Page 2 of 3)
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of acetazolamide have not been conducted. In a bacterial mutagenicity assay, acetazolamide 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 dose of 1000 mg in a 50 kg individual.
Pregnancy: Teratogenic effects
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.
Because of the potential for serious adverse reactions in nursing infants from acetazolamide, 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.
The safety and effectiveness of acetazolamide in pediatric patients have not been established.
Growth retardation has been reported in children receiving long-term therapy, believed secondary to chronic acidosis.
Metabolic acidosis, which can be severe, may occur in the elderly with reduced renal function.
Clinical studies of acetazolamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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 of concomitant disease or other drug therapy.
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, thrombocytopenia, 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/hypoglycaemia
Nervous: Drowsiness, paraesthesia (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. 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
To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc. at 1-877-244-9825 or go to www.strides.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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, acetazolamide is dialyzable. This may be particularly important in the management of acetazolamide overdosage when complicated by the presence of renal failure.
DOSAGE AND ADMINISTRATION
Glaucoma: Acetazolamide should be used as an adjunct to the usual therapy. The dosage employed in the treatment of chronic simple(open-angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours, usually in divided doses for amounts over 250 mg. It has usually been found that a dosage in excess of 1 g per 24 hours does not produce an increased effect. In all cases, the dosage should be adjusted with careful individual attention both to symptomatology and ocular tension. Continuous supervision by a physician is advisable.
In treatment of secondary glaucoma and in the preoperative treatment of some cases of acute congestive (closed-angle) glaucoma , the preferred dosage is 250 mg every four hours, although some cases have responded to 250 mg twice daily on short-term therapy. In some acute cases, it may be more satisfactory to administer an initial dose of 500 mg followed by 125 mg or 250 mg every four hours depending on the individual case. Intravenous therapy may be used for rapid relief of ocular tension in acute cases. A complementary effect has been noted when acetazolamide has been used in conjunction with miotics or mydriatics as the case demanded.
Epilepsy: It is not clearly known whether the beneficial effects observed in epilepsy are due to direct inhibition of carbonic anhydrase in the central nervous system or whether they are due to the slight degree of acidosis produced by the divided dosage. The best results to date have been seen in petit mal in pediatric patients. Good results, however, have been seen in patients, both pediatric patients and adult, in other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns, etc. The suggested total daily dose is 8 to 30 mg per kg in divided doses. Although some patients respond to a low dose, the optimum range appears to be from 375 to 1000 mg daily. However, some investigators feel that daily doses in excess of 1 g do not produce any better results than a 1 g dose. When acetazolamide tablets are given in combination with other anticonvulsants, it is suggested that the starting dose should be 250 mg once daily in addition to the existing medications. This can be increased to levels as indicated above.
The change from other medications to acetazolamide should be gradual and in accordance with usual practice in epilepsy therapy.
Congestive Heart Failure: For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg/kg). If, after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day. Acetazolamide tablets yield best diuretic results when given on alternate days, or for two days alternating with a day of rest.
Failures in therapy may be due to overdosage or too frequent dosage. The use of acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.
Drug-Induced Edema: Recommended dosage is 250 to 375 mg of acetazolamide once a day for one or two days, alternating with a day of rest.
Acute Mountain Sickness: 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.
Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from the inhibitory effect of the therapeutic agent.
Interference with Laboratory Tests
Sulfonamides may give false negative or decreased values for urinary phenolsulfonphthalein and phenol red elimination values for urinary protein, serum non-protein and for 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.
Acetazolamide Tablets USP are supplied as follows:
125 mg – White to off white, round, flat, uncoated tablet, debossed as “S;571” on one side and scored in half on other side
NDC 72789-045-06 — Bottle of 6
NDC 72789-045-12 — Bottle of 12
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
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