What is Diamox (acetazolamide)?

What is Diamox (Acetazolamide)?

Diamox (acetazolamide) is a potent carbonic anhydrase inhibitor—a sulfonamide derivative that works by blocking the enzyme carbonic anhydrase, which catalyzes the reversible reaction between carbon dioxide hydration and carbonic acid dehydration throughout the body. 1

Mechanism of Action

Acetazolamide inhibits carbonic anhydrase enzymes, producing multiple physiologic effects across different organ systems 1:

• In the kidneys: Blocks the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid, resulting in renal loss of bicarbonate ions that carry out sodium, water, and potassium, leading to urinary alkalinization and diuresis 1

• In the eye: Decreases secretion of aqueous humor, resulting in reduced intraocular pressure 1

• In the brain: Decreases cerebrospinal fluid (CSF) production, reducing intracranial pressure, and appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons 1, 2

• At altitude: Induces metabolic acidosis that stimulates respiratory drive, leading to increased ventilation even during sleep and improved arterial oxygen saturation 3

FDA-Approved Indications

Acetazolamide is approved for 1:

• Glaucoma: Control of fluid secretion in certain types of glaucoma 4, 1
• Epilepsy: Treatment of certain convulsive disorders 1
• Edema: Promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema) 1
• Altitude sickness: Prevention and treatment 3

Common Off-Label Uses

While not FDA-approved for these conditions, acetazolamide is used off-label for 4, 2:

• Obstructive sleep apnea (OSA): Can reduce sleep apnea intensity (AHI) by up to 45% in unselected groups, though the European Respiratory Society suggests use only in research settings as there is no approved label for OSA 4
• Idiopathic intracranial hypertension/pseudotumor cerebri: To reduce elevated intracranial pressure and avoid invasive procedures 5, 2
• Ventilator weaning: For chronic obstructive pulmonary disease patients 2
• Prevention of high-dose methotrexate toxicity and contrast-induced nephropathy 2

Dosing and Pharmacokinetics

• Available forms: Oral tablets and intravenous powder requiring reconstitution 1
• Dosage range: 250 to 4,000 mg daily divided every 6-12 hours, depending on indication 2
• Plasma half-life: 4-8 hours, though pharmacologic effects last longer 2
• Protein binding: Highly protein bound 2
• Elimination: Primarily renal; administration should not be more frequent than every 12 hours if creatinine clearance is less than 50 mL/min 2

Common Side Effects

Acetazolamide causes frequent, dose-dependent side effects 5, 6:

• Paresthesias: Most common side effect, affecting approximately 1 in 2-3 patients (Number Needed to Harm = 2.3), with risk increasing significantly at higher doses 5, 6
• Dysgeusia (altered taste): Occurs in approximately 1 in 18 patients (NNH = 18), dose-dependent 5, 6
• Polyuria: NNH = 17 6
• Fatigue: Occurs in approximately 1 in 11 patients (NNH = 11), with trend toward dose-dependence 5, 6
• Vertigo and unpleasant taste 4, 5
• Tinnitus 5
• Cognitive slowing and depression: Particularly concerning for patients requiring mental acuity 5
• Nausea, vomiting, and diarrhea 5

Serious Adverse Effects

• Electrolyte imbalances: Particularly hypokalemia, requiring monitoring 5
• Renal stones: Rare but recognized complication 5
• Acidotic state: Can occur, particularly in overdose 5
• Stevens-Johnson syndrome: Rare but serious 4
• Blood dyscrasias: Including aplastic anemia and thrombocytopenia 4

Contraindications

Absolute contraindications include 4:

• Sulfonamide allergy (acetazolamide is a sulfonamide derivative) 4, 1
• Kidney stones 4
• Aplastic anemia 4
• Sickle cell disease 4
• Pregnancy: Due to potential teratogenic risks 5

Clinical Tolerability

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. This highlights the importance of starting with lower doses (250-500 mg twice daily) and titrating gradually to minimize the initial side effect burden 5.

Important Clinical Pearls

• Acetazolamide is not a mercurial diuretic but rather a carbonic anhydrase inhibitor with a chemical structure and pharmacological activity distinctly different from bacteriostatic sulfonamides 1
• The drug may reduce blood pressure, particularly at high altitude (systolic reduction of 7-10 mmHg) 4, 5, 3
• Adequate hydration must be maintained as dehydration can worsen symptoms in conditions like altitude sickness 3
• For altitude sickness prevention, acetazolamide should be started 1-3 days prior to ascent and continued for 3-4 days after reaching terminal altitude 3