(ah-seet-a-zole-a-mide)
Diamox®, Dazamide®
CARBONIC ANHYDRASE INHIBITOR DIURETIC; ANTIGLAUCOMA AGENT
Acetazolamide has been used principally in veterinary medicine for its effects on aqueous humor production in the treatment of glaucoma, metabolic alkalosis, and for its diuretic action. It may be useful as an adjunctive treatment for syringomyelia in dogs. Acetazolamide’s use in small animals is complicated by a relatively high occurrence of adverse effects.
In horses, acetazolamide is used as an adjunctive treatment for hyperkalemic periodic paralysis (HYPP).
In humans, the drug has been used as adjunctive therapy for epilepsy and for acute high-altitude sickness.
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 thereby reducing the availability of these ions for active transport into body secretions.
Pharmacologic effects of the carbonic anhydrase inhibitors include: decreased formation of aqueous humor, thus reducing intraocular pressure, increased renal tubular secretion of sodium and potassium and, to a greater extent, bicarbonate, leading to increased urine alkalinity and volume.
Acetazolamide has some anticonvulsant activity, which is independent of its diuretic effects (mechanism is not fully understood, but may be due to carbonic anhydrase or a metabolic acidosis effect).
In anesthetized cats, methazolamide did not, but acetazolamide did reduce the hypoxic ventilatory response. The authors believe this not as a result of carbonic anhydrase inhibition, but due to acetazolamide’s effects on carotid bodies or type I cells (Teppema et al. 2006).
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 is about 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 (in 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.
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 that are unable to increase alveolar ventilation or in those who are hypersensitive to them. Long-term use of carbonic anhydrase inhibitors is contraindicated in patients with chronic, noncongestive, angleclosure 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 having preexisting hematologic abnormalities. Cross sensitivity between acetazolamide and antibacterial sulfonamides may occur.
Potential adverse effects that may be encountered include: GI disturbances, CNS effects (sedation, depression, weakness, excitement, etc.), hematologic effects (bone marrow depression), renal effects (crystalluria, dysuria, renal colic, polyuria), hypokalemia, hyperglycemia, hyponatremia, hyperuricemia, hepatic insufficiency, dermatologic effects (rash, etc.), and hypersensitivity reactions.
At the dosages used for HYPP in horses adverse effects are reportedly uncommon.
Acetazolamide has been implicated in fetal abnormalities in mice and rats when used at high (10X) dosages and fetal toxicity has been noted when the drug has been used in pregnant humans. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)
In humans, the manufacturer states that either nursing or the drug must be discontinued if the mother is receiving acetazolamide. Veterinary significance is not clear.
Information regarding overdosage of this drug was not located. In the event of an overdose, it is recommended to contact an animal poison control center. Monitor serum electrolytes, blood gases, volume status, and CNS status during an acute overdose; treat symptomatically and supportively.
The following drug interactions have either been reported or are theoretical in humans or animals receiving acetazolamide and may be of significance in veterinary patients:
By alkalinizing the urine, carbonic anhydrase inhibitors may cause false positive results in determining urine protein when 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
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.
For adjunctive treatment of metabolic alkalosis:
a) 10 mg/kg four times daily (may aggravate volume contraction and hypokalemia) (Hardy and Robinson 1986)
For adjunctive therapy of glaucoma:
a) 10–25 mg/kg divided 2–3 times daily (Brooks 2002)
b) 50–75 mg/kg PO 2–3 times a day (Bedford 2003)
c) 50 mg/kg IV one time; 7 mg/kg, PO three times daily (Vestre 1985)
For adjunctive therapy of hydrocephalus in pediatric patients:
a) 0.1 mg/kg PO q8h (Coates 2002)
For adjunctive therapy of glaucoma:
a) 50 mg/kg IV once; 7 mg/kg, PO three times daily (Vestre 1985)
For adjunctive therapy of hyperkalemic periodic paralysis (HYPP):
a) 2.2–4.4 mg/kg PO twice daily (Schott II 2004)
b) 0.5–2.2 mg/kg PO twice daily (Mayhew 2005)
c) 2–3 mg/kg PO q8-12h when diet adjustment does not control episodes. (Valberg 2008)
a) 6–8 mg/kg IV, IM, or SC (Howard 1986)
a) 6–8 mg/kg IV, IM, or SC (Howard 1986)
Give with food if using oral preparation and GI upset occurs
Notify veterinarian if abnormal bleeding or bruising occurs or if animal develops tremors or a rash
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, sparingly soluble in hot water (90–100°C) and alcohol. Acetazolamide 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.
Acetazolamide may also known as: acetazolam, acetazolamidum, or sodium acetazolamide; many trade names are available.
Acetazolamide products should be stored at room temperature. To prepare parenteral solution: reconstitute with at least 5 mL of Sterile Water for Injection. 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.
COMPOUNDED PREPARATION STABILITY: Acetazolamide oral suspension compounded from commercially available tablets has been published (Allen, 1996). Triturating twelve (12) 250 mg tablets with 60 mL of Ora-Plus® and qs ad to 120 mL with Ora-Sweet® (or Ora-Sweet® SF) yields a 25 mg/mL suspension that retains >90% potency for 60 days stored at both 5°C and 25°C. The stability of acetazolamide aqueous liquids decreases at pH values above 9. The optimal stability is reported to be between 3 and 5. Compounded preparations of acetazolamide should be protected from light.
VETERINARY-LABELED PRODUCTS: None
The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.
HUMAN-LABELED PRODUCTS:
Acetazolamide Oral Tablets: 125 mg, 250 mg; generic; (Rx)
Acetazolamide Extended-Release Oral Capsules: 500 mg; Diamox Sequels® (Barr); generic (Rx)
Acetazolamide Injection (lyophilized powder for solution): 500 mg; generic; (Rx)