What are the uses and dosages of Diamox (acetazolamide)?

Diamox (Acetazolamide): Clinical Uses and Dosing

Acetazolamide is a carbonic anhydrase inhibitor with FDA-approved indications for glaucoma, epilepsy, congestive heart failure, and drug-induced edema, with established off-label uses for altitude sickness prevention and idiopathic intracranial hypertension. 1

FDA-Approved Indications and Dosing

Glaucoma

• Chronic open-angle glaucoma: 250 mg to 1 g per 24 hours in divided doses (amounts >250 mg should be divided); dosages exceeding 1 g per 24 hours typically do not produce increased effect 1
• Secondary glaucoma and acute closed-angle glaucoma: 250 mg every 4 hours, though some cases respond to 250 mg twice daily 1
• Acute cases: Initial 500 mg followed by 125-250 mg every 4 hours; IV therapy may be used for rapid relief of ocular tension 1

Epilepsy

• Pediatric and adult dosing: 8-30 mg/kg/day in divided doses, with optimal range 375-1000 mg daily 1
• Starting dose when adding to existing anticonvulsants: 250 mg once daily, then titrate upward 1
• Best results seen in petit mal seizures in children, though effective in grand mal and other seizure patterns 1

Congestive Heart Failure (Diuresis)

• Starting dose: 250-375 mg once daily in the morning (5 mg/kg) 1
• Optimal regimen: Alternate-day dosing or 2 days on/1 day off to allow kidney recovery 1
• If edema fluid loss stops, skip medication for a day rather than increasing dose 1

Drug-Induced Edema

• Dosing: 250-375 mg once daily for 1-2 days, alternating with a day of rest 1

Key Off-Label Uses

Altitude Sickness Prevention

• Standard prophylactic dose: 250 mg twice daily or 500 mg once daily 2
• Lower effective dose: 125 mg twice daily (250 mg/day total) has similar efficacy with potentially fewer side effects 2
• For rapid ascent >3,500 m (military/emergency personnel): 500-750 mg/day appears most effective 3
• Timing: Start 1-3 days prior to ascent and continue for 3-4 days after reaching terminal altitude 2
• Mechanism: Induces metabolic acidosis that stimulates respiratory drive, improves arterial oxygen saturation (88-91% at altitude), and reduces periodic breathing 2

Important caveat: Acetazolamide 62.5 mg twice daily failed noninferiority testing and should NOT be recommended, with a number needed to harm of 9 compared to 125 mg twice daily 4

Idiopathic Intracranial Hypertension (IIH)

• Starting dose: 250-500 mg twice daily, with majority of clinicians titrating upward 5
• Maximum studied dose: 4 g daily (only 44% of patients tolerate this dose) 5
• Typical tolerated dose: 1-1.5 g daily (48% discontinue at mean 1.5 g/day due to side effects) 5, 6
• Pediatric dosing: Initial 25 mg/kg/day, titrate to clinical response (maximum 100 mg/kg/day) 6

Critical limitation: Acetazolamide has NOT been shown effective for headache treatment alone in IIH 5, 6

Obstructive Sleep Apnea (Research Setting Only)

• Dose range studied: 36-1000 mg daily for up to 3 months 6
• Effect: Reduces apnea-hypopnea index by up to 45% and improves oxygen saturation 6
• Guideline position: European Respiratory Society recommends use only in research settings, not routine clinical practice 6

Side Effect Profile and Management

Most Common Side Effects (Dose-Dependent)

• Paraesthesias: Occur in approximately 1 in 2-3 patients (number needed to harm = 2.3); risk increases significantly with higher doses 6, 7
• Dysgeusia (taste disturbance): 1 in 18 patients; dose-dependent 6, 7
• Fatigue: 1 in 11 patients; trend toward dose-dependence 6, 7
• Polyuria: Number needed to harm = 17 7
• Tinnitus, nausea, vomiting, diarrhea: Well-documented 5, 6
• Cognitive slowing and depression: Particularly concerning for patients requiring mental acuity 5, 6

Serious Adverse Effects

• Renal stones: Rare but recognized complication 5, 6
• Electrolyte imbalances (hypokalemia): Requires monitoring 6, 8
• Metabolic acidosis: Can occur, particularly in overdose 6

Contraindications and Special Populations

• Pregnancy: Contraindicated due to teratogenic risks 6
• Renal impairment: Dosing should not be more frequent than every 12 hours if creatinine clearance <50 mL/min 9
• Sulfonamide allergy: Acetazolamide is a sulfonamide derivative 9
• Diabetic patients: Monitor electrolytes and blood glucose; consider metabolic effects carefully 8

Practical Prescribing Strategy

Minimizing Side Effects

• Start low and go slow: Begin with 250-500 mg twice daily and titrate gradually 5, 6
• Consider lower doses for altitude sickness: 125 mg twice daily is effective with fewer side effects than higher doses 2
• Avoid excessive dosing: Higher doses increase side effect burden without proportional benefit in many conditions 5, 1

Monitoring Requirements

• Electrolytes: Monitor for hypokalemia, particularly in diabetic patients 6, 8
• Renal function: Adjust dosing frequency with impaired creatinine clearance 9
• Clinical response: In IIH, 48% discontinue due to side effects at mean 1.5 g/day 6

Route of Administration

• Oral preferred for most indications 1
• IV route: Preferred for parenteral administration when needed (acute glaucoma, rapid ICP reduction) 1
• IM route: Not recommended 1