What are the doses of acetazolamide and mannitol for reducing intraocular pressure (IOP)?

Acetazolamide and Mannitol Dosing for IOP Reduction

For acute IOP reduction, use acetazolamide 250 mg every 4 hours (or 500 mg initial dose followed by 125-250 mg every 4 hours) and mannitol 20% solution at 1 g/kg IV over 30 minutes. 1, 2

Acetazolamide Dosing

Acute Angle-Closure Crisis

• Initial dose: 500 mg IV or PO, followed by 125-250 mg every 4 hours depending on severity and response 1, 2
• Some acute cases respond to 250 mg every 4 hours without the loading dose 1, 2
• IV administration is preferred for rapid IOP relief in acute situations 3, 2

Chronic Open-Angle Glaucoma

• Daily dose range: 250 mg to 1 g per 24 hours, usually in divided doses for amounts over 250 mg 1, 2
• Doses exceeding 1 g per 24 hours typically do not produce increased therapeutic effect 1, 2

Pharmacokinetic Considerations

• Maximum IOP reduction occurs approximately 2 hours after oral administration 4
• Doses as low as 63 mg can produce significant IOP reduction (average 8.2 mm Hg fall), with minimal additional benefit from higher doses 4
• Plasma levels of 4-5 μg/mL are as effective as levels of 10 μg/mL or higher 4
• The maximal IOP effect is typically a 30-35% reduction from baseline 4

Dose Adjustment for Renal Function

• Oral clearance is directly related to creatinine clearance 5
• Recommended dosing based on creatinine clearance:
  • CCR 70 mL/min: 250 mg three times daily 5
  • CCR 50 mL/min: 125 mg three times daily 5
  • CCR 30 mL/min: 125 mg twice daily 5
  • CCR 10 mL/min: 125 mg once daily 5

Mannitol Dosing

Standard Dosing Protocol

• Dose: 20% solution at 1 g/kg body weight administered IV over 30 minutes 6
• This dosing is effective in both vitrectomized and nonvitrectomized eyes 6

Time Course of IOP Reduction

• Significant IOP reduction begins at 30 minutes post-administration 6
• Maximum effect typically occurs between 90-120 minutes 6
• IOP reduction persists for at least 4 hours after administration 6
• Average IOP reduction: from approximately 48-49 mm Hg to 33-36 mm Hg at 4 hours 6

Clinical Pearls and Pitfalls

Acetazolamide

• Lower doses (63-125 mg) may be sufficient for many patients, avoiding unnecessary side effects while maintaining efficacy 4
• Doses should be adjusted in divided portions when exceeding 250 mg daily 1, 2
• Complementary effects occur when combined with miotics or mydriatics as clinically indicated 3, 1, 2
• Systemic side effects include Stevens-Johnson syndrome, electrolyte disturbances, and kidney stones 7

Mannitol

• Equally effective in vitrectomized silicon oil-filled eyes and nonvitrectomized open-angle eyes 6
• No significant difference in IOP-lowering effect between these two populations at any time point 6
• Should be used as part of acute management while preparing for definitive treatment (laser iridotomy) 3

Combined Approach

• Medical therapy including acetazolamide and mannitol is typically initiated first in acute angle-closure to lower IOP and clear corneal edema before performing iridotomy 3
• Carbonic anhydrase inhibitors may be initially less effective if ciliary body ischemia is present from markedly elevated IOP 3