Chemistry - A carbonic anhydrase inhibitor, acetazolamide occurs as a white to faintly yellowish-white, odorless, crystalline powder with pKas of 7.4 and 9.1. It is very slightly soluble in water and sparingly soluble in hot water (90-100°C), and sparingly soluble in alcohol. Acetozolamide sodium occurs as a white lyophilized solid and is freely soluble in water. The injection has a pH of 9.2 after reconstitution with Sterile Water for Injection.
Storage/Stability/Compatibility - Acetazolamide products should be stored at room temperature. After reconstitution, the injection is stable for one week when refrigerated, but as it contains no preservatives, it should be used within 24 hours.
Acetazolamide sodium for injection is reportedly physically compatible with all commonly used IV solutions and cimetidine HCl for injection.
Pharmacology - The carbonic anhydrase inhibitors act by a noncompetitive, reversible inhibition of the enzyme carbonic anhydrase. This reduces the formation of hydrogen and bicarbonate ions from carbon dioxide and reduces the availability of these ions for active transport into body secretions.
Pharmacologic effects of the carbonic anhydrase inhibitors include decreased formation of aqueous humor, thereby reducing intraocular pressure; increased renal tubular secretion of sodium and potassium and, to a greater extent, bicarbonate, leading to increased urine alkalinity and volume; anticonvulsant activity, which is independent of its diuretic effects (mechanism not fully understood, but may be due to carbonic anhydrase or a metabolic acidosis effect).
Uses/Indications - Acetazolamide is used principally in veterinary medicine for its effects on aqueous humor production in the treatment of glaucoma. It has also been used for its diuretic action and in the treatment of metabolic alkalosis. In humans, the drug has been used as adjunctive therapy for epilepsy and for acute high-altitude sickness.
Pharmacokinetics - The pharmacokinetics of this agent have apparently not been studied in domestic animals. One report (Roberts 1985) states that after a dose of 22 mg/kg, the onset of action is 30 minutes; maximal effects occur in 2-4 hours; duration of action of 4-6 hours in small animals.
In humans, the drug is well absorbed after oral administration with peak levels occurring within 1 - 3 hours. It is distributed throughout the body with highest levels found in the kidneys, plasma and erythrocytes. Acetazolamide has been detected in the milk of lactating dogs and it crosses the placenta (unknown quantities). Within 24 hours of administration, an average of 90% of the drug is excreted unchanged into the urine by tubular secretion and passive reabsorption processes.
Contraindications/Precautions - Carbonic anhydrase inhibitors are contraindicated in patients with significant hepatic disease (may precipitate hepatic coma), renal or adrenocortical insufficiency, hyponatremia, hypokalemia, hyperchloremic acidosis or electrolyte imbalance. They should not be used in patients with severe pulmonary obstruction unable to increase alveolar ventilation or those who are hypersensitive to them. Long term use of carbonic anhydrase inhibitors are contraindicated in patients with chronic, noncongestive, angle-closure glaucoma as angle closure may occur and the drug may mask the condition by lowering intraocular pressures.
Acetazolamide should be used with caution in patients with severe respiratory acidosis or who have preexisting hematologic abnormalities. Cross sensitivity between acetazolamide and antibacterial sulfonamides may occur.
Adverse Effects/Warnings - Potential adverse effects that may be encountered include GI disturbances, CNS effects (sedation, depression, excitement, etc.), hematologic effects (bone marrow depression), renal effects (crystalluria, dysuria, renal colic, polyuria), hypokalemia, hyperglycemia, hyponatremia, hyperuricosemia, hepatic insufficiency, dermatologic effects (rash, etc.), and hypersensitivity reactions.
Overdosage - Information regarding overdosage of this drug is not readily available. It is suggested to monitor serum electrolytes, blood gases, volume status, and CNS status during an acute overdose. Treat symptomatically and supportively.
Drug Interactions - Oral acetozolamide can inhibit primidone absorption. Primidone or phenytoin, used with acetazolamide, may cause severe osteomalacia.
Because acetozolamide alkalinizes the urine, the excretion rates of many drugs (e.g., quinidine, procainamide, phenobarbital, methotrexate, etc.) may be affected. It may also negate the effects of methenamine compounds in the urine.
Concomitant use with corticosteroids, amphotericin B, corticotropin, or other diuretics may exacerbate potassium depletion; this may be especially significant in patients receiving digitalis preparations.
Rarely, carbonic anhydrase inhibitors interfere with the hypoglycemic effects of insulin.
Laboratory Interactions - By alkalinizing the urine, carbonic anhydrase inhibitors may cause false positive results in determining urine protein using bromphenol blue reagent (Albustix®, Albutest®, Labstix®), sulfosalicylic acid (Bumintest®, Exton’s Test Reagent), nitric acid ring test, or heat and acetic acid test methods.
Carbonic anhydrase inhibitors may decrease iodine uptake by the thyroid gland in hyperthyroid or euthyroid patients.
Doses - Directions for reconstitution of injection: Reconstitute 500 mg vial with at least 5 ml of Sterile Water for Injection; use within 24 hours after reconstitution.
a) 6 - 8 mg/kg IV, IM, or SQ (Howard 1986)
Monitoring Parameters - 1) Intraocular pressure/tonometry (if used for glaucoma); blood gases if used for alkalosis; 2) Serum electrolytes; 3) Baseline CBC with differential and periodic retests if using chronically; 4) Other adverse effects
Client Information - If using oral preparation and GI upset occurs, give with food. Notify veterinarian if abnormal bleeding or bruising occurs or if animal develops tremors or a rash.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Acetazolamide 125 mg, 250 mg Tablets; Diamox ® ;(Lederle) (Rx); .i.Dazamide® (Major) (Rx); generic (Rx)
Acetazolamide Extended-release Capsules 500mg; Diamox Sequels® (Lederle); generic (Rx)
Acetazolamide Injection: 500 mg per vial; Diamox®; (Lederle);
Acetazolamide Powder 500 mg for Reconstitution; Diamox® (Lederle); Generic; (Rx)
To prepare parenteral solution: Reconstitute with at least 5 ml of Sterile Water for Injection. If refrigerated, potency will remain for 1 week, but it should be used within 24 hours as it contains no preservatives.
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