Acetazolamide

Carbonic anhydrase inhibitor Diuretic; Antiglaucoma agent; Anticonvulsant

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 5-10 mg/kg q8-12h Duration: Varies with condition; for glaucoma, often used short-term (days to weeks)
Notes: For glaucoma, use in combination with topical therapy. For epilepsy, start at low end and titrate. Monitor electrolytes and acid-base status.
Dog IV 5-10 mg/kg q8-12h Duration: For acute glaucoma or when oral not possible
Notes: Administer slowly. Use only if oral route is not feasible.
Cat PO 5-10 mg/kg q12h Duration: Short-term for glaucoma or hydrocephalus
Notes: Use cautiously in cats; may cause metabolic acidosis. Monitor renal function.
Horse PO 1-3 mg/kg q12-24h Duration: For HYPP: often used intermittently or as needed
Notes: For HYPP, dose may be adjusted based on potassium levels. For glaucoma, use as adjunct.
Cattle PO 5-10 mg/kg q12-24h Duration: Short-term for metabolic alkalosis
Notes: Extra-label use; observe withdrawal times.
Rabbit PO 5-10 mg/kg q12h Duration: Short-term for glaucoma
Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications
  • Reduction of intraocular pressure in glaucoma
  • Reduction of cerebrospinal fluid production in hydrocephalus
  • Diuresis and alkalinization of urine
  • Adjunct treatment of metabolic alkalosis
  • Adjunct anticonvulsant in certain epilepsies
Dog (Canine)
  • Adjunct therapy for glaucoma (to reduce intraocular pressure)
  • Primary glaucoma (short-term management before surgery)
  • Hydrocephalus (to reduce CSF production)
  • Metabolic alkalosis (as a diuretic)
  • Urine alkalinization (to enhance excretion of weak acids)
  • Idiopathic epilepsy (as an adjunct anticonvulsant)
  • Altitude sickness (prevention/treatment, off-label)
Cat (Feline)
  • Adjunct therapy for glaucoma (less common than in dogs)
  • Hydrocephalus (off-label)
  • Urine alkalinization (off-label)
  • Idiopathic epilepsy (off-label)
Horse (Equine)
  • Equine glaucoma (adjunct therapy)
  • Hyperkalemic periodic paralysis (HYPP) – to reduce episodes (off-label)
  • Metabolic alkalosis (off-label)
Cattle (Bovine)
  • Urine alkalinization (off-label)
Exotic & Other Species
  • Reptiles: may be used for gout (off-label)
  • Small mammals: limited use

Pharmacology & Mechanism of Action

Drug Class: Carbonic anhydrase inhibitor | Pharmacological Group: Diuretic; Antiglaucoma agent; Anticonvulsant

Mechanism of Action: Acetazolamide is a potent, reversible inhibitor of the enzyme carbonic anhydrase. This enzyme catalyzes the hydration of carbon dioxide to carbonic acid and the dehydration of carbonic acid to carbon dioxide. In the kidney, inhibition of carbonic anhydrase in the proximal convoluted tubule reduces the reabsorption of bicarbonate, leading to increased excretion of bicarbonate, sodium, potassium, and water, producing an alkaline diuresis. In the eye, inhibition of carbonic anhydrase in the ciliary body reduces aqueous humor production, thereby lowering intraocular pressure. In the central nervous system, inhibition of carbonic anhydrase in the choroid plexus reduces cerebrospinal fluid production and may have anticonvulsant effects by altering pH and ion gradients.

Pharmacodynamics: Acetazolamide produces a self-limiting diuresis because the metabolic acidosis that develops from bicarbonate loss reduces the effectiveness of the drug after a few days of continuous use. It lowers intraocular pressure by 40-60% in glaucomatous eyes, with maximal effect within 2-4 hours after oral administration. It also reduces cerebrospinal fluid pressure and can be used to treat certain types of epilepsy, particularly in dogs. The drug may cause metabolic acidosis, hypokalemia, and hyperchloremia with chronic use.

⚡ Pharmacokinetics Summary

Absorption: Acetazolamide is well absorbed after oral administration in most species. Peak plasma concentrations occur within 1-2 hours in dogs and cats. The presence of food may delay absorption but not the extent.
Distribution: Acetazolamide is widely distributed throughout the body, including the eye and cerebrospinal fluid. It crosses the placenta and is distributed into milk. It is bound to plasma proteins to a moderate extent (approximately 60-90% in humans, but species-specific data are limited).
Metabolism: Acetazolamide is not extensively metabolized; the majority of the drug is excreted unchanged in the urine. A small portion may be metabolized via hepatic acetylation.
Excretion: Acetazolamide is primarily excreted by the kidney via tubular secretion. Renal excretion is rapid, with most of the dose eliminated within 24 hours. In animals with renal impairment, excretion is reduced, and dosage adjustment may be necessary.
Half-Life: Dog: approximately 2-4 hours; Cat: approximately 3-6 hours; Horse: approximately 1-2 hours; Cattle: approximately 2-3 hours (estimated).
Bioavailability: Oral bioavailability is high, typically >90% in dogs and cats.
Protein Binding: Approximately 60-90% (species-dependent; higher in humans, lower in some animals).

Available Formulations & Strengths

Oral Tablet 125 mg, 250 mg (PO)
Injectable Solution 500 mg vial (powder for reconstitution) (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to acetazolamide or other sulfonamides
  • Severe renal or hepatic disease
  • Hyponatremia or hypokalemia
  • Adrenal insufficiency
  • Severe respiratory acidosis
  • Concurrent use with high-dose aspirin (may increase salicylate toxicity)
Warnings & Clinical Precautions:
  • Use with caution in patients with diabetes mellitus (may increase blood glucose)
  • Use with caution in patients with gout or uric acid kidney stones (may increase uric acid excretion)
  • May cause metabolic acidosis; monitor acid-base status during prolonged therapy
  • May cause hypokalemia; monitor serum potassium
  • In animals with hepatic impairment, may precipitate hepatic encephalopathy
  • In pregnant animals, use only if clearly needed; safety not established
  • In lactating animals, use with caution; drug is excreted in milk
  • Do not use in animals with severe pulmonary disease (may worsen respiratory acidosis)
  • May cause drowsiness or ataxia; caution when performing tasks requiring alertness

Adverse Effects & Reactions

Common:

  • Polyuria
  • Polydipsia
  • Anorexia
  • Vomiting
  • Diarrhea
  • Lethargy
  • Metabolic acidosis
  • Hypokalemia
  • Hyperchloremia

Serious / Severe:

  • Severe metabolic acidosis
  • Renal calculi (calcium phosphate stones)
  • Blood dyscrasias (rare but possible: aplastic anemia, agranulocytosis)
  • Hepatic necrosis (rare)
  • Stevens-Johnson syndrome (rare)

Rare:

  • Paresthesia
  • Tinnitus
  • Transient myopia
  • Photosensitivity
  • Bone marrow suppression

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Aspirin and other salicylates Increased risk of salicylate toxicity due to decreased renal excretion and metabolic acidosis High
Corticosteroids Increased risk of hypokalemia Moderate
Amphotericin B Increased risk of hypokalemia Moderate
Lithium Increased lithium excretion, reduced efficacy Moderate
Primidone May decrease serum primidone levels Mild
Phenytoin May increase risk of osteomalacia Mild
Cyclosporine May increase cyclosporine levels (theoretical) Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe metabolic acidosis
  • Hyperventilation
  • Lethargy
  • Confusion
  • Seizures
  • Coma
  • Hypokalemia
  • Dehydration

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Correct fluid and electrolyte imbalances with IV fluids. Administer sodium bicarbonate to correct severe acidosis (but use cautiously to avoid overcorrection). Monitor acid-base status, serum electrolytes, and renal function. In severe cases, hemodialysis may be considered.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not officially established for acetazolamide in food animals; these are conservative estimates. Consult regulatory guidelines and use extra-label with caution. For cattle, a withdrawal time of at least 7 days for meat and 3 days for milk is recommended.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (15-30°C / 59-86°F)

Handling & Special Conditions: Protect from moisture. Keep container tightly closed. Reconstituted injectable solution should be used within 24 hours if refrigerated.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. Veterinary use is extra-label.

Extra-Label (Off-Label) Use: In the US, acetazolamide is not FDA-approved for veterinary use in most species; use is extra-label. Under AMDUCA, extra-label use is permitted in animals by or on the order of a licensed veterinarian, provided a valid VCPR exists and appropriate withdrawal times are observed. In food animals, extra-label use is prohibited if an approved animal drug exists that is labeled for the condition and contains the same active ingredient in the same dosage form, unless the veterinarian determines it is ineffective or unavailable.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Acetazolamide is a versatile drug in veterinary medicine, primarily used for its ability to reduce intraocular pressure in glaucoma and to decrease cerebrospinal fluid production in hydrocephalus. It is also used as an adjunct anticonvulsant and for metabolic alkalosis. In horses, it is used off-label for hyperkalemic periodic paralysis (HYPP) to help prevent episodes. The drug is generally well-tolerated but requires monitoring of electrolytes and acid-base status, especially with prolonged use. Because it is a sulfonamide derivative, caution is advised in animals with sulfonamide hypersensitivity. In food animals, extra-label use requires careful attention to withdrawal times. Always use the lowest effective dose for the shortest duration necessary. For glaucoma, acetazolamide is not a substitute for topical therapy but can be a valuable adjunct. In emergency situations, IV administration may be used, but oral therapy is preferred for maintenance. Patient response should be monitored by measuring intraocular pressure, seizure frequency, or clinical signs of hydrocephalus. Periodic blood work, including serum electrolytes, BUN, creatinine, and blood gas analysis, is recommended during chronic therapy.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)