What is Diamox (acetazolamide)?

What is Diamox (Acetazolamide)?

Diamox (acetazolamide) is a carbonic anhydrase inhibitor that works by blocking the enzyme carbonic anhydrase throughout the body, leading to decreased fluid secretion in the eye, reduced abnormal brain electrical activity, and increased urinary excretion of bicarbonate with sodium, water, and potassium. 1

Mechanism of Action

Acetazolamide specifically inhibits carbonic anhydrase, the enzyme catalyzing the reversible reaction between carbon dioxide hydration and carbonic acid dehydration 1:

• In the eye: Decreases aqueous humor secretion, lowering intraocular pressure 1
• In the brain: Decreases cerebrospinal fluid production, reducing intracranial pressure; retards abnormal, excessive neuronal discharge in the central nervous system 1, 2
• In the kidneys: Causes renal loss of bicarbonate ion, carrying out sodium, water, and potassium, resulting in urinary alkalinization and diuresis 1

FDA-Approved Indications

Acetazolamide is approved for 1, 2:

• Glaucoma (certain types requiring control of fluid secretion)
• Epilepsy (certain convulsive disorders)
• Edema (abnormal fluid retention, particularly cardiac edema)
• Altitude sickness (prevention and treatment)

Common Off-Label Uses

Obstructive Sleep Apnea

• The European Respiratory Society recommends acetazolamide only in research settings for OSA, as there is no approved label for this indication 3
• Can reduce sleep apnea intensity (AHI) by up to 45% in unselected patient groups 3
• Improves oxygen desaturation index and oxygenation 3
• Does not improve excessive daytime sleepiness 3
• Dose range studied: 36-1000 mg daily for up to 3 months 3

High Altitude Applications

• Reduces nocturnal oxygen desaturation at altitude (increases saturation by 1-2% to 91-88%) 3
• Decreases blood pressure increases at altitude (7-10 mmHg systolic reduction) 3
• For rapid ascents >3,500 m, doses of 500-750 mg/day within 24 hours of exposure are most effective 4

Idiopathic Intracranial Hypertension

• Initial dose: 25 mg/kg/day, titrated upward until clinical response (maximum 100 mg/kg/day) 5
• Acetazolamide has not been shown effective for headache treatment alone in this condition 5

Pharmacokinetics

• Plasma half-life: 4-8 hours, though pharmacologic effects last longer 2
• Protein binding: Highly protein bound 2
• Elimination: Primarily renal 2
• Dosing adjustment: Administration should not be more frequent than every 12 hours if creatinine clearance <50 mL/min 2

Side Effects Profile

Most Common (Dose-Dependent)

• Paraesthesias: Occur in approximately 1 in 2-3 patients (number needed to harm = 2.3); risk increases significantly with higher doses 5, 6
• Dysgeusia (metallic taste): Affects 1 in 18 patients; dose-dependent 3, 5, 6
• Polyuria: Affects 1 in 17 patients 5, 6
• Fatigue: Occurs in 1 in 11 patients; trend toward dose-dependence 5, 6
• Nausea and vomiting 5
• Vertigo 3
• Tinnitus 5

Serious Adverse Effects

• Electrolyte imbalances, particularly hypokalemia, requiring monitoring 5, 7
• Renal stones (rare but recognized) 5
• Metabolic acidosis, particularly in overdose 5
• Cognitive slowing and depression 5
• Blood dyscrasias (aplastic anemia, thrombocytopenia) 3
• Stevens-Johnson syndrome 3

Clinical Tolerance

In clinical practice, 48% of patients discontinue acetazolamide at mean doses of 1.5 g/day due to side effects, while only 44% tolerate the maximum 4 g/day dose 5

Contraindications

• Sulfonamide allergy 3
• Kidney stones 3
• Aplastic anemia 3
• Sickle cell disease 3
• Pregnancy (potential teratogenic risks) 5

Dosing Strategy to Minimize Side Effects

Start low (250-500 mg twice daily) and titrate gradually to minimize initial side effect burden 5. This approach balances efficacy with tolerability, particularly important given the high discontinuation rates at higher doses.

Special Populations

Diabetic Patients

• Monitor electrolytes carefully, particularly potassium 7
• Consider alternative preventive strategies for altitude sickness when possible 7
• Use only in research settings for OSA with careful consideration of metabolic effects 7

Cardiovascular Patients

• Concomitant administration with other diuretics may increase dehydration and electrolyte imbalance risk at high altitude 3
• May be helpful for reducing subendocardial ischemia risk at altitude, though no data exist in patients with coronary artery disease 3

Important Clinical Caveats

• Not a mercurial diuretic; it is a non-bacteriostatic sulfonamide with distinct pharmacological activity from bacteriostatic sulfonamides 1
• Side effects are class-specific for carbonic anhydrase inhibitors (including topiramate and zonisamide) 3
• Long-term safety data remain limited for many indications 3
• Cognitive symptoms are not uncommon with carbonic anhydrase inhibitors 3