What are the indications for acetazolamide?

Indications for Acetazolamide

Acetazolamide is indicated for acute heart failure with diuretic resistance, acute mountain sickness prophylaxis, idiopathic intracranial hypertension, glaucoma, chronic mountain sickness, and metabolic alkalosis from diuretic therapy, with emerging evidence supporting its use in acute decompensated heart failure as adjunctive therapy to loop diuretics. 1

FDA-Approved and Guideline-Supported Indications

Acute Heart Failure with Diuretic Resistance

• In hospitalized patients with acute heart failure, acetazolamide added to loop diuretics significantly improves decongestion (42.2% vs 30.5% success rate) within 3 days, with enhanced natriuresis and urine volume. 1
• The mechanism involves proximal tubule sodium reabsorption inhibition and pendrin pathway blockade, providing sequential nephron blockade to overcome adaptive resistance mechanisms. 1
• This indication is supported by the ADVOR trial (519 patients), though hard endpoints like mortality and rehospitalization showed no difference. 1
• Acetazolamide should be given intravenously once daily in addition to standard loop diuretic regimens for patients with volume overload despite adequate loop diuretic dosing. 1

Acute Mountain Sickness (AMS) Prophylaxis

• Acetazolamide is highly effective for preventing acute mountain sickness, causing marked reduction in headache, nausea, vomiting, and weakness through increased arterial oxygen concentrations. 2
• The European Society of Cardiology recommends acetazolamide for AMS prevention in cardiovascular patients ascending to high altitude, as it may reduce subendocardial ischemia risk. 1
• Acetazolamide improves nocturnal oxygen saturation and reduces blood pressure increases (systolic reduction 7-10 mmHg) at high altitude. 3
• Dosing typically ranges from 250-500 mg daily, started before ascent. 3

Chronic Mountain Sickness (Monge's Disease)

• Acetazolamide (250-500 mg daily) is the first efficient pharmacologic treatment for chronic mountain sickness, reducing hematocrit by 7.1%, serum erythropoietin by 67%, and apnea-hypopnea episodes by 74% over 3 weeks. 4
• It increases nocturnal arterial oxygen saturation by 5% and decreases mean nocturnal heart rate by 11%. 4
• This represents a major public health intervention for high-altitude populations (above 3,200 m) where prevalence reaches 5-18%. 4

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

• Initial dosing is 25 mg/kg/day, titrated upward until clinical response, with maximum 100 mg/kg/day. 3
• Acetazolamide decreases cerebrospinal fluid production and reduces intracranial pressure, avoiding invasive procedures. 5
• In pediatric patients, use reduced dose of 25 mg/m². 3
• Note: Acetazolamide has not been shown effective for headache treatment alone in this condition. 3

Glaucoma (Acute Angle-Closure and Open-Angle)

• Acetazolamide reduces aqueous humor production, lowering intraocular pressure. 5
• Particularly useful in acute angle-closure glaucoma as emergency treatment. 6
• Dosing ranges from 250-1000 mg daily depending on severity. 5

Metabolic Alkalosis (Diuretic-Induced Chloride Depletion)

• Acetazolamide inhibits proximal sodium bicarbonate reabsorption, increasing urinary bicarbonate excretion to correct metabolic alkalosis, particularly post-hypercapnic alkalosis. 7
• Useful in critically ill patients with diuretic-induced alkalosis, though optimal dosing and duration remain uncertain. 7
• Case reports demonstrate success in diverse populations including pediatric heart disease patients and COPD patients. 7
• This indication is particularly relevant in ICU settings for ventilator weaning. 5, 6

Off-Label Uses with Limited Evidence

Obstructive Sleep Apnea (OSA)

• The European Respiratory Society suggests using acetazolamide only in research settings for OSA, as it can reduce apnea-hypopnea index by up to 45% in unselected groups. 3
• The American College of Physicians states that pharmacologic agents including acetazolamide lack sufficient evidence for routine prescription as primary OSA treatment, with CPAP and weight loss being first-line. 3
• Dosing in trials ranges from 36-1000 mg daily for up to 3 months. 3

COPD Ventilator Weaning

• Limited literature supports acetazolamide for ventilator weaning in COPD patients with metabolic alkalosis. 5
• May help correct post-hypercapnic alkalosis facilitating extubation. 6

Prevention of Methotrexate Toxicity and Contrast-Induced Nephropathy

• Urinary alkalinization may prevent high-dose methotrexate toxicity and contrast-induced nephropathy, though evidence is limited. 5

Dosing Considerations

• Standard dosing ranges from 250-4000 mg daily divided every 6-12 hours, with plasma half-life of 4-8 hours but longer pharmacologic effects. 5
• Start low (250-500 mg twice daily) and titrate gradually to minimize side effects, as 48% of patients discontinue at mean doses of 1.5 g/day due to adverse effects. 3
• Reduce dosing frequency to no more than every 12 hours if creatinine clearance is less than 50 mL/min due to renal elimination. 5

Critical Contraindications and Warnings

• Absolutely contraindicated in patients with known sulfonamide allergy, aplastic anemia, sickle cell disease, and pregnancy (Category C). 8
• Contraindicated with kidney stones, marked hepatic damage, or severe renal insufficiency when function cannot be monitored. 8
• Monitor serum electrolytes (particularly potassium and chloride) and renal function, as hypokalemia and hyperchloremia are serious adverse effects. 8
• Concomitant administration with other diuretics increases dehydration and electrolyte imbalance risk at high altitude. 1