Acetazolamide Prophylaxis for High-Altitude Travel
Yes, prescribing acetazolamide (Diamox) for healthy adult travelers ascending to altitudes above 2,500 m is appropriate and strongly recommended as first-line prophylaxis for acute mountain sickness. 1
Primary Recommendation
Acetazolamide 250 mg twice daily (or 500 mg once daily) should be started 1 day before ascent above 2,500-3,000 m and continued for 2-3 days after reaching terminal altitude. 1, 2 This dosing provides optimal efficacy with a favorable side-effect profile compared to higher doses. 3
Supporting Evidence
Efficacy Data
- Acetazolamide reduces the risk of acute mountain sickness by 48% compared to placebo in meta-analysis. 3
- The risk of altitude illness with rapid ascent above 3,350 m ranges from 35-50%, comparable to traveler's diarrhea risk in high-risk destinations, making prophylaxis highly justified. 2
- In controlled trials on Kilimanjaro (5,895 m), acetazolamide users reached higher altitudes (11 vs 4 reached summit) and had significantly lower symptom scores (mean 4.8 vs 14.3) compared to placebo. 4
Mechanism and Benefits
- Acetazolamide works as a carbonic anhydrase inhibitor, causing mild diuresis and metabolic acidosis that stimulates ventilation and improves oxygenation. 1
- It lowers blood pressure at high altitude while improving oxygen saturation and mountain sickness symptoms. 5, 1
- May reduce subendocardial ischemia risk at high altitude in healthy subjects. 1
Dosing Considerations
The 250 mg twice daily dose (or 500 mg once daily) is preferred over higher doses because:
- No evidence shows increased efficacy with doses above 250 mg twice daily. 3
- Adverse effects are dose-related, so lower effective doses minimize side effects. 3
- A single 500 mg morning dose provides comparable efficacy with potentially better compliance. 6
Critical Prescribing Caveats
When NOT to Prescribe
Do not prescribe acetazolamide for:
- Travelers to moderate altitudes (e.g., Grand Canyon at ~2,100 m) with planned descent within 24 hours. 7
- Situations where altitude exposure and activity fall outside clinical practice guidelines (>2,500 m threshold). 7
Important Safety Warnings
- Dehydration risk: Acetazolamide is a diuretic; inadequate hydration combined with exertion can lead to acute kidney injury, particularly when combined with rhabdomyolysis risk. 7
- Patients must maintain adequate hydration throughout altitude exposure. 1, 7
- Common but generally mild adverse effects include paresthesias, vertigo, and unpleasant taste. 1
Non-Pharmacologic Measures (Essential Adjuncts)
Acetazolamide should complement, not replace, proper acclimatization strategies:
- Ascend at 300-600 m/day above 2,500 m. 1
- Include rest day for every 600-1,200 m elevation gained. 1
- Avoid vigorous exertion before acclimatization. 1
- Delay further ascent if symptoms appear. 1
Special Populations
Cardiovascular Disease Patients
- Patients with pre-existing cardiovascular conditions should continue regular medications and can add acetazolamide using the same dosing protocol. 1
- Hypertensive patients may particularly benefit as acetazolamide lowers blood pressure at altitude. 5, 1
- When used with other diuretics in heart failure patients, carefully monitor for dehydration and electrolyte imbalances. 1
Women
- No clear evidence of greater vulnerability to acute mountain sickness in women, though sex-dependent physiological reactions may contribute to increased vulnerability in some. 1
- Acetazolamide prophylaxis is equally appropriate for women travelers. 1
Duration of Therapy
Prolonged use beyond 2-3 days at terminal altitude is unnecessary for standard acute mountain sickness prevention and increases cumulative side effects. 1 The medication can be discontinued after the acclimatization period at target altitude.