What is the recommended dosing for acetazolamide (carbonic anhydrase inhibitor)?

Acetazolamide Dosing

Acetazolamide dosing varies significantly by indication, with glaucoma requiring 250-1000 mg daily in divided doses, epilepsy requiring 8-30 mg/kg daily (375-1000 mg), and idiopathic intracranial hypertension requiring 250-500 mg twice daily as a starting dose, titrated upward to a maximum of 4 g daily as tolerated. 1, 2

Dosing by Indication

Glaucoma

• Chronic open-angle glaucoma: 250-1000 mg per 24 hours in divided doses for amounts over 250 mg 1
• Doses exceeding 1 g per 24 hours typically do not produce increased therapeutic effect 1
• Secondary glaucoma and acute closed-angle glaucoma: 250 mg every 4 hours, though some cases respond to 250 mg twice daily 1
• For acute cases, consider an initial dose of 500 mg followed by 125-250 mg every 4 hours 1
• Sustained-release formulations: 500 mg once daily provides substantial pressure-lowering effect lasting at least 23 hours, though 500 mg twice daily is as effective as 250 mg tablets four times daily 3
• Therapeutic serum concentrations of 15-20 mcg/mL achieve approximately 45% reduction in outflow pressure 3

Idiopathic Intracranial Hypertension (IIH) / Pseudotumor Cerebri

• Starting dose: 250-500 mg twice daily, which is the most commonly recommended initial regimen 2
• Titration: Increase dose based on clinical response and tolerability 2
• Maximum dose: Up to 4 g daily has been used in clinical studies, though only 44% of patients tolerate this high dose 2
• Pediatric dosing: 25 mg/kg/day initially, titrated to maximum 100 mg/kg/day 2
• Nearly 48% of patients discontinue acetazolamide at mean doses of 1.5 g due to side effects 2
• Acetazolamide is not effective for headache alone in IIH patients 2

Epilepsy

• Total daily dose: 8-30 mg/kg in divided doses 1
• Optimal range: 375-1000 mg daily, with best results seen in petit mal seizures in children 1
• Doses exceeding 1 g daily do not appear to produce better results than 1 g 1
• When adding to existing anticonvulsants: Start with 250 mg once daily, then increase as indicated 1
• The mechanism may involve direct carbonic anhydrase inhibition in the CNS or slight acidosis from divided dosing 1

Congestive Heart Failure / Edema

• Starting dose: 250-375 mg once daily in the morning (5 mg/kg) 1
• Optimal regimen: Alternate-day dosing or 2 days on with 1 day of rest yields best diuretic results 1
• If initial response fails to continue, skip medication for a day to allow kidney recovery rather than increasing dose 1
• This differs from glaucoma/epilepsy dosing because diuresis depends on carbonic anhydrase inhibition in the kidney, which requires intermittent dosing for recovery 1

Drug-Induced Edema

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

Altitude Sickness Prevention

• Low-dose regimen: 125 mg twice daily (250 mg total daily) is as effective as 375 mg twice daily (750 mg total daily) for preventing acute mountain sickness 4
• The lower dose produces less paresthesia (p < 0.02) 4
• Both doses improve oxygenation equally (82.9% vs 82.8%) compared to placebo (80.7%) 4

Renal Dosing Adjustments

• Creatinine clearance <50 mL/min: Do not administer more frequently than every 12 hours 5
• End-stage renal disease on CAPD: Elimination half-life is markedly prolonged to 28.5 hours (vs 5-10 hours in normal renal function) 6
• For ESRD patients, marked dose reduction is required—consider 125 mg daily or less to prevent drug accumulation and toxicity 6
• CAPD removes only 6.8% of the dose, which is not clinically significant 6

Pharmacokinetics

• Plasma half-life: 4-8 hours in normal renal function, though pharmacologic effects last longer 5
• Protein binding: Highly protein bound 5
• Elimination: Primarily renal 5
• Dosing frequency: Typically ranges from every 6-12 hours depending on indication 5

Common Pitfalls and Caveats

• Overdosing in heart failure: Failures in therapy are often due to overdosage or too frequent dosing rather than inadequate dose 1
• Continuous daily dosing in edema: This prevents kidney recovery from carbonic anhydrase inhibition; intermittent dosing is essential 1
• High discontinuation rates: 48% of patients discontinue at mean doses of 1.5 g due to side effects including gastrointestinal, neurological, sensory, psychiatric, and renal effects 2
• Toxicity in renal impairment: Lethargy and other signs of toxicity can occur with standard dosing in patients with reduced kidney function 6
• Sustained-release formulations: These reduce plasma concentration fluctuations and substantially decrease incidence of drowsiness, tingling extremities, and confusion compared to immediate-release tablets 7

Contraindications and Warnings

• Sulfonamide allergy: Acetazolamide is a sulfonamide derivative and should not be used in allergic patients 5
• Severe liver disease: Contraindicated 8
• Adrenal gland failure and hyperchloremic acidosis: Contraindicated 8
• Pregnancy: FDA Category C—potential fetal risks based on animal studies 8
• Hematologic monitoring: Rare blood dyscrasias including aplastic anemia and thrombocytopenia can occur 8
• Renal effects: Increased risk of kidney stones 8
• CNS effects: Confusion, depression, and cognitive slowing, particularly at higher doses 8