Acetazolamide is a first-generation, non-competitive, reversible inhibitor of carbonic anhydrase (CA), primarily CA-II. It is a sulfonamide derivative used as a diuretic, antiglaucoma agent, and for the prevention and treatment of acute mountain sickness. It reduces aqueous humor production in the eye and promotes renal excretion of bicarbonate, sodium, potassium, and water, leading to metabolic acidosis which can be therapeutic in certain conditions.
Adult: Glaucoma: 250 mg to 1 g per day in divided doses (commonly 250 mg 1-4 times daily). AMS: 125-250 mg every 8-12 hours, starting 24-48 hours before ascent. Epilepsy: 8-30 mg/kg/day in divided doses, usually 250-1000 mg daily. Idiopathic Intracranial Hypertension: 250 mg 2-3 times daily.
Note: Oral tablet. Can be taken with or without food. Taking with food may reduce GI upset. Swallow whole with a full glass of water. Maintain adequate hydration. For altitude sickness, start 24-48 hours before ascent and continue for 48 hours after reaching maximum altitude or upon descent.
Acetazolamide is a potent, reversible inhibitor of the enzyme carbonic anhydrase (CA), particularly the cytosolic isoform CA-II. By inhibiting CA in the renal proximal tubule, it prevents the reabsorption of bicarbonate (HCO3-), sodium (Na+), and water, leading to a bicarbonate diuresis and mild metabolic acidosis. In the eye, inhibition of CA in the ciliary body epithelium reduces the formation of aqueous humor, thereby lowering intraocular pressure (IOP). In the central nervous system, CA inhibition may reduce abnormal neuronal excitability and CSF production.
Pregnancy: FDA Pregnancy Category C. Animal studies have shown teratogenicity (limb defects). Use only if the potential benefit justifies the potential risk to the fetus, especially in the first trimester. Not recommended for prophylaxis of AMS in pregnancy.
Driving: May cause drowsiness, fatigue, dizziness, and paresthesia. Patients should be cautioned about operating machinery or driving until they know how the drug affects them.
| Aspirin (high-dose, salicylates) | Increased risk of metabolic acidosis, CNS toxicity; may displace acetazolamide from protein binding. | Major |
| Other Diuretics (e.g., Furosemide, Thiazides) | Additive hypokalemia and diuretic effect. | Major |
| Sodium Bicarbonate, Antacids | May decrease effectiveness of acetazolamide by counteracting metabolic acidosis. | Moderate |
| Methenamine | Acetazolamide alkalinizes urine, reducing the efficacy of methenamine which requires acidic urine. | Moderate |
| Cyclosporine | Increased risk of cyclosporine-induced hyperuricemia and gout; acetazolamide may increase cyclosporine levels. | Moderate |
| Primidone, Phenobarbital | Increased risk of osteomalacia with long-term concurrent use. | Moderate |
| Lithium | Increased renal excretion of lithium, potentially decreasing its efficacy. | Moderate |
| Hypoglycemic agents (e.g., Insulin, Sulfonylureas) | Acetazolamide may alter blood glucose levels; monitoring required. | Moderate |
| Quinidine | Alkalinization of urine decreases quinidine excretion, increasing its toxicity risk. | Moderate |
| Amphetamines, Procainamide | Alkalinization of urine decreases their excretion, increasing toxicity risk. | Moderate |