What are the indications and dosing guidelines for Acetazolamide (carbonic anhydrase inhibitor) IV?

Acetazolamide IV: Indications and Dosing

Acetazolamide IV is indicated for glaucoma (250 mg to 1 g per 24 hours in divided doses), epilepsy (8-30 mg/kg/day divided), congestive heart failure diuresis (250-375 mg once daily), and drug-induced edema (250-375 mg once daily for 1-2 days alternating with rest), with the direct intravenous route preferred over intramuscular administration. 1

Primary Indications and Dosing

Glaucoma

• Chronic simple (open-angle) glaucoma: 250 mg to 1 g per 24 hours, usually in divided doses for amounts over 250 mg 1
• Dosages exceeding 1 g per 24 hours typically do not produce increased therapeutic effect 1
• Secondary glaucoma and acute congestive (closed-angle) glaucoma: 250 mg every 4 hours as preferred dosage 1
• Acute cases: Initial dose of 500 mg followed by 125-250 mg every 4 hours depending on individual response 1
• IV therapy provides rapid relief of ocular tension in acute cases 1
• The 45% reduction in outflow pressure is achieved with serum concentrations of 15-20 micrograms/mL 2

Epilepsy

• Dosing range: 8-30 mg/kg per day in divided doses 1
• Optimal range: 375-1000 mg daily, though some investigators believe doses exceeding 1 g daily provide no additional benefit 1
• Starting dose when combined with other anticonvulsants: 250 mg once daily, then titrate upward 1
• The mechanism may involve direct carbonic anhydrase inhibition in the CNS or mild acidosis from divided dosing 1
• Best results have been seen in petit mal seizures in pediatric patients, though effectiveness extends to grand mal, mixed patterns, and myoclonic jerks 1

Congestive Heart Failure

• 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 edema fluid loss stops after initial response, skip medication for a day to allow kidney recovery rather than increasing the dose 1
• Does not eliminate need for digitalis, bed rest, and salt restriction 1

Drug-Induced Edema

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

Off-Label Uses with Evidence

Metabolic Alkalosis in Critical Care

• Single dose: 500 mg IV effectively corrects metabolic alkalosis in critically ill patients 3
• Correction of pH (from 7.49 to 7.46) is maximal at 24 hours and sustained for 72 hours 3
• Mechanism involves decreasing serum strong ion difference through increased renal sodium excretion without chloride, resulting in increased serum chloride 3

Acute Mountain Sickness Prevention

• Effective dose: 250 mg/day provides similar efficacy to higher doses with a more favorable side-effect profile 4
• Acetazolamide prophylaxis produces a 48% relative-risk reduction compared to placebo 4
• Improvements correlate with increased arterial oxygen concentrations and reduction in proteinuria and peripheral edema 5

Pseudotumor Cerebri (PTC) in Pediatrics

• Initial dose: 25 mg/kg per day, titrated upward until clinical response (maximum 100 mg/kg per day) 6
• Electrolytes must be monitored for hypokalemia and acidosis 6
• If acetazolamide is ineffective, prednisone 2 mg/kg per day for 2 weeks followed by 2-week taper can be added 6

Obstructive Sleep Apnea

• Reduces AHI by up to 45% in unselected patient groups 6
• Improves oxygen desaturation index and oxygenation 6
• Current recommendation: Use only in context of RCTs due to lack of approved label for OSA and incomplete long-term outcome data 6

Elevated Intracranial Pressure

• Decreases CSF production, reducing ICP and potentially avoiding invasive procedures 7
• May be used for elevated ICP due to CSF leaks 7

Important Contraindications and Precautions

Specific Contraindication

• Should NOT be used to reduce intracranial pressure in cryptococcal meningitis (DIII recommendation from CDC) 8

Administration Guidelines

• Preferred route: Direct intravenous administration 1
• Intramuscular administration is NOT recommended 1
• Reconstituted solutions retain properties for 3 days refrigerated (2-8°C) or 12 hours at room temperature (20-25°C) 1
• Contains no preservative 1

Renal Dosing

• Plasma half-life is 4-8 hours, though pharmacologic effects last longer 7
• Creatinine clearance <50 mL/min: Do not administer more frequently than every 12 hours 7
• Primarily eliminated by kidneys 7

Common Adverse Effects

• Paresthesias, vertigo, and unpleasant taste are class-specific effects 6
• Cognitive symptoms can occur with carbonic anhydrase inhibitors 6
• May produce increased level of crystals in urine 1

Key Clinical Pearls

Dosing Frequency Differences by Indication

• Glaucoma and epilepsy: Do not require intermittent dosing as they are not dependent on carbonic anhydrase inhibition in the kidney 1
• Heart failure and edema: Require intermittent dosing to allow kidney recovery from inhibitory effects 1

Laboratory Interference

• May give false negative or decreased values for urinary phenolsulfonphthalein and phenol red elimination 1
• Interferes with HPLC method for theophylline assay (depends on extraction solvent) 1
• May produce false values for urinary protein, serum non-protein, and serum uric acid 1

Pediatric Considerations

• ATRA-associated headache/PTC: Use reduced ATRA dose (25 mg/m² vs 45 mg/m²) to minimize need for acetazolamide 6
• Distinguish PTC from CNS leukemia or bleeding through CSF analysis and imaging 6
• Symptoms may resolve with initial diagnostic lumbar puncture alone 6