What is the use of Diamox (acetazolamide)?

Acetazolamide (Diamox): Uses and Clinical Applications

Acetazolamide (Diamox) is a potent carbonic anhydrase inhibitor primarily used for glaucoma, altitude sickness prevention, certain seizure disorders, and as a diuretic for abnormal fluid retention, with emerging evidence supporting its use in obstructive sleep apnea in research settings only. 1, 2

Mechanism of Action

• Acetazolamide inhibits carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid 1
• This inhibition leads to reduced hydrogen ion secretion in the proximal renal tubule, resulting in increased bicarbonate and cation excretion, causing urinary alkalization and diuresis 3
• In the eye, this inhibitory action decreases aqueous humor secretion, resulting in reduced intraocular pressure 1
• It also decreases cerebrospinal fluid production, which reduces intracranial pressure 3

FDA-Approved Indications

• Glaucoma management (by reducing intraocular pressure) 1
• Treatment of certain convulsive disorders (epilepsy) 1
• Promotion of diuresis in instances of abnormal fluid retention (cardiac edema) 1
• Altitude sickness prevention and treatment 4

Off-Label Uses

• Obstructive Sleep Apnea (OSA)

  • Can reduce sleep apnea intensity (AHI) by up to 45% in unselected groups 2
  • Improves oxygen saturation and reduces oxygen desaturation index 2
  • European Respiratory Society suggests use only in research settings as there is no approved label for OSA 2
  • No documented effect on excessive daytime sleepiness 2

• High Altitude Applications

  • Reduces excessive blood pressure increases at high altitude (7-10 mmHg systolic reduction) 2
  • Improves nocturnal oxygen saturation at altitude 2
  • Reduces acute mountain sickness symptoms with 48% relative risk reduction compared to placebo 5
  • For rapid ascent to elevations >3,500m, doses of 500-750 mg/day appear most effective 4

• Other Off-Label Uses

  • Idiopathic intracranial hypertension/pseudotumor cerebri 3
  • CSF leak management 3
  • Potential aid in ventilator weaning for COPD patients 3

Dosing Considerations

• For altitude sickness: 250 mg/day has similar efficacy to higher doses with potentially fewer side effects 5
• For OSA trials: dose range is 36-1000 mg daily, with treatment periods up to 3 months 2
• For idiopathic intracranial hypertension: initial dose is 25 mg/kg/day, titrated upward as needed 6
• Dosage adjustment required in renal impairment (should not be administered more frequently than every 12 hours if creatinine clearance is <50 mL/min) 3

Side Effects and Monitoring

• Common side effects include:

  • Paresthesias (numbness/tingling) - number needed to harm: 2.3 7
  • Dysgeusia (taste disturbances) - number needed to harm: 18 7
  • Polyuria - number needed to harm: 17 7
  • Fatigue - number needed to harm: 11 7
  • Vertigo and unpleasant taste 2

• Risk of paresthesias and taste disturbances increases with higher doses 7

• Electrolyte imbalances, particularly hypokalemia, require monitoring 8

• Blood glucose levels should be monitored in diabetic patients 8

Special Considerations

• When used with other diuretics at high altitude, increased risk of dehydration and electrolyte imbalances 2
• In diabetic patients, careful consideration of potential metabolic effects is required 8
• Acetazolamide is a sulfonamide derivative, so caution is needed in patients with sulfa allergies 3
• Plasma half-life is 4-8 hours, though pharmacologic effects last longer 3

Clinical Pearls

• For altitude sickness prevention, acetazolamide should be started 24-48 hours before ascent 4, 9
• Lower doses (250 mg/day) may provide similar efficacy with fewer side effects for altitude sickness 5
• Alternative preventive strategies for altitude sickness should be considered in patients with contraindications 2
• Acetazolamide can reduce periodic breathing in heart failure patients at high altitude, though this requires further clarification 2