What are the uses and dosages of Acetazolamide (carbonic anhydrase inhibitor) in various medical conditions?

Acetazolamide: Uses and Dosages in Various Medical Conditions

Acetazolamide is a versatile carbonic anhydrase inhibitor used for multiple medical conditions with specific dosing regimens ranging from 125-1000 mg daily depending on the indication, with effectiveness demonstrated for glaucoma, epilepsy, altitude sickness, edema, and idiopathic intracranial hypertension. 1

Primary Indications and Dosages

Glaucoma

• Dosage: 250 mg to 1 g daily, usually in divided doses for amounts over 250 mg 2
• Used as adjunctive therapy to usual glaucoma treatments
• For secondary glaucoma and preoperative treatment of acute congestive (closed-angle) glaucoma: 250 mg every four hours 2
• Some acute cases may respond better to an initial dose of 500 mg followed by 125-250 mg every four hours 2
• The American Academy of Ophthalmology supports these dosing recommendations 1

Epilepsy

• Dosage: 8-30 mg/kg daily in divided doses 2
• Optimum range: 375-1000 mg daily 2
• When adding to existing anticonvulsants: Start with 250 mg once daily 2
• Most effective for petit mal seizures in children, but also beneficial for grand mal, mixed seizure patterns, and myoclonic jerk patterns 2
• Transition from other medications should be gradual 2

Altitude Sickness

• Dosage: 125-250 mg twice daily, starting 24 hours before ascent 1
• Reduces risk of acute mountain sickness by 48% compared to placebo 3
• Lower dose of 62.5 mg twice daily has been shown to be non-inferior to 125 mg twice daily in prevention 4
• Improves nocturnal oxygenation at high altitudes 1

Congestive Heart Failure

• Dosage: 250-375 mg once daily in the morning (5 mg/kg) 2
• Most effective when given on alternate days or for two days alternating with a day of rest 2
• Does not eliminate need for other therapy such as digitalis, bed rest, and salt restriction 2

Drug-Induced Edema

• Dosage: 250-375 mg once daily for one or two days, alternating with a day of rest 2

Off-Label Uses

Obstructive Sleep Apnea

• The European Respiratory Society suggests use only in the context of clinical trials 5
• Can reduce sleep apnea intensity by up to 45% 5
• Improves nocturnal oxygenation, especially at high altitudes 5
• Not approved for OSA treatment 5

Idiopathic Intracranial Hypertension

• Reduces cerebrospinal fluid production and intracranial pressure 6
• Can help avoid invasive procedures in patients with CSF leaks or elevated ICP 6

Other Uses

• Ventilator weaning for COPD patients 6
• Prevention of high-dose methotrexate toxicity 6
• Prevention of contrast-induced nephropathy 6

Contraindications and Precautions

• Contraindicated in:

  • Sulfonamide allergy 1
  • Severe hepatic disease 1
  • Severe renal disease 1
  • Adrenocortical insufficiency 1
  • Hyperchloremic acidosis 1
  • Kidney stones 5
  • Aplastic anemia 5
  • Sickle cell disease 5

• Dosage adjustment:

  • For creatinine clearance <50 mL/min, do not administer more frequently than every 12 hours 6

Adverse Effects

• Common side effects:

  • Paresthesias 5, 1
  • Vertigo 5, 1
  • Altered taste 1
  • Allergic dermatitis/conjunctivitis 5
  • Malaise, anorexia, depression 5

• Serious side effects:

  • Kidney stones 5, 7
  • Metabolic acidosis 5, 7
  • Blood dyscrasias (aplastic anemia, thrombocytopenia) 5
  • Stevens-Johnson syndrome 5
  • Serum electrolyte imbalances 5

Monitoring Recommendations

• Monitor serum electrolytes, particularly for hypokalemia 1
• Monitor renal function 1
• Monitor acid-base status 1
• Watch for signs of dehydration, especially when combined with other diuretics 1
• Avoid combining with other diuretics due to increased risk of dehydration and electrolyte imbalances 1

Clinical Pearls

• Acetazolamide's pharmacologic effects last longer than its 4-8 hour plasma half-life 6
• For altitude sickness, proper acclimatization remains essential (gradual ascent of 300-600m/day above 2500m) 1
• Immediate descent is the primary treatment for severe altitude illness, regardless of medication use 1
• Side effects appear to be dose-related, suggesting that using the lowest effective dose may improve tolerability 4
• When used for epilepsy, partial tolerance may develop to the antiepileptic activity 7