What are the indications, dosages, and potential side effects of Azetazolamide (carbonic anhydrase inhibitor)?

Acetazolamide: Indications, Dosages, and Potential Side Effects

Acetazolamide should be used primarily for approved indications including glaucoma, epilepsy, altitude sickness, and edema, while its use for obstructive sleep apnea should be limited to research settings due to limited evidence on long-term outcomes. 1

Approved Indications

• Altitude Sickness: Acetazolamide is effective for prevention and treatment of acute mountain sickness (AMS) when ascending to elevations above 1,500m 2
• Glaucoma: Reduces intraocular pressure by decreasing aqueous humor production 3
• Epilepsy: Used as adjunctive therapy with other antiepileptic medications for various seizure types including partial, myoclonic, absence, and primary generalized tonic-clonic seizures 4
• Idiopathic Intracranial Hypertension: Decreases cerebrospinal fluid production, reducing intracranial pressure 3
• Edema: Functions as a mild diuretic 3

Off-Label Uses (Limited Evidence)

• Obstructive Sleep Apnea (OSA): European Respiratory Society guidelines suggest using acetazolamide only in research settings, as there is no approved label for OSA 1

  • Can reduce sleep apnea intensity (AHI) by up to 45% in unselected groups 1
  • Improves oxygen saturation and reduces oxygen desaturation index 1
  • No documented effect on excessive daytime sleepiness 1

• High Altitude Sleep Disorders: Studies show improved nocturnal oxygen saturation and reduced blood pressure increases at high altitude 1

Dosage Recommendations

• Altitude Sickness Prevention:

  • For rapid ascent to >3,500m: 500-750 mg/day within 24 hours of altitude exposure 2
  • For moderate ascent to >3,000m: 250 mg daily 5

• Obstructive Sleep Apnea (research setting only):

  • Dose range in trials: 36-1000 mg daily 1
  • Treatment periods up to 3 months 1

• Idiopathic Intracranial Hypertension/Pseudotumor Cerebri:

  • Initial dose: 25 mg/kg/day
  • Titrate upward until clinical response (maximum 100 mg/kg/day) 1

• Renal Impairment: Administration should not be more frequent than every 12 hours if creatinine clearance is less than 50 mL/min 3

Side Effects and Adverse Reactions

• Common Side Effects:

  • Paresthesias (numbness/tingling): Number needed to harm (NNH) = 2.3 6
  • Taste disturbances (dysgeusia): NNH = 18 6
  • Polyuria: NNH = 17 6
  • Fatigue: NNH = 11 6
  • Vertigo and unpleasant taste 1

• Serious Adverse Effects:

  • Metabolic acidosis 3, 4
  • Electrolyte imbalances (particularly hypokalemia) 1
  • Kidney stones 4
  • Blood dyscrasias (rare): anaphylaxis, fever, rash, crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis 7

• Dose-Dependent Side Effects: Risk of paresthesias and dysgeusia increases significantly with higher doses 6

Special Populations and Precautions

• Pregnancy: Category C - should be used only if potential benefit justifies potential risk to fetus 7

  • Shown to be teratogenic (limb defects) in animal studies 7

• Nursing Mothers: Should only be used if potential benefit justifies potential risk to the child 7

• Pediatric Use: Safety and effectiveness in children not established 7

  • For pseudotumor cerebri in children, reduced dose of 25 mg/m² is recommended 1

• Pulmonary Obstruction/Emphysema: Use with caution as it may precipitate or aggravate acidosis 7

• Monitoring Requirements:

  • Baseline CBC and platelet count before initiating therapy and at regular intervals 7
  • Periodic monitoring of serum electrolytes 7
  • Monitor for development of acidotic state 7

Important Clinical Considerations

• Drug Interactions: Caution advised for patients receiving concomitant high-dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy, coma, and death have been reported 7

• Tolerance: Partial tolerance may develop to the antiepileptic activity 4

• Overdose Management:

  • Monitor serum electrolyte levels (particularly potassium) and blood pH 7
  • Administer bicarbonate to correct acidotic state 7
  • Despite high protein binding, acetazolamide may be dialyzable 7

• Cardiovascular Effects: May reduce blood pressure, particularly at high altitude (systolic reduction of 7-10 mmHg) 1