From the Guidelines
For high altitude prophylaxis, acetazolamide is typically dosed at 125 mg twice daily, starting 24 hours before ascent and continuing for 48 hours after reaching the target altitude, as recommended by recent guidelines 1. This dosing regimen is supported by the most recent and highest quality study, which emphasizes the importance of proper acclimatization, gradual ascent, staying hydrated, and avoiding alcohol and smoking to prevent high altitude illness, including acute mountain sickness. Some key points to consider when using acetazolamide for high altitude prophylaxis include:
- The medication should be taken with food to minimize gastrointestinal side effects
- Acetazolamide works by causing a mild metabolic acidosis through carbonic anhydrase inhibition, which stimulates ventilation and increases oxygenation, effectively speeding up acclimatization
- Common side effects include increased urination, tingling sensations in the extremities, and altered taste of carbonated beverages
- Individuals with sulfa allergies should avoid acetazolamide
- Those with kidney disease or severe hepatic insufficiency should consult their physician before using acetazolamide as dosage adjustments may be necessary It's worth noting that some clinicians recommend a higher dose of 250 mg twice daily for individuals with a history of acute mountain sickness or for those ascending rapidly to very high altitudes (above 3500 meters) 1. However, the standard dosing regimen of 125 mg twice daily is generally recommended and effective for most individuals. Other studies, such as 2, 3, 4, and 5, provide varying dosing regimens, but these are older studies and not as relevant to current clinical practice. In real-life clinical medicine, it's essential to prioritize the most recent and highest quality evidence, which in this case supports the standard dosing regimen of 125 mg twice daily for high altitude prophylaxis.
From the Research
Acetazolamide Dosing for High Altitude Prophylaxis
- The recommended dosage of acetazolamide for high altitude prophylaxis varies, with studies suggesting doses ranging from 125 mg to 750 mg per day 6, 7, 8.
- A study published in 2019 found that day of ascent dosing of acetazolamide demonstrated higher rates of acute mountain sickness (AMS) compared to traditional dosing, but with similar rates of severe AMS and overall symptom severity 6.
- Another study published in 2021 recommended doses of 500-750 mg/day within 24 hours of altitude exposure for military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m 7.
- A systematic review and meta-analysis published in 2012 found that acetazolamide prophylaxis was associated with a 48% relative-risk reduction compared to placebo, with no evidence of an association between efficacy and dose of acetazolamide 8.
- A study published in 2014 suggested that pre-treatment with low-dose acetazolamide on the day before ascending to high altitude tended to reduce AMS incidence on the first day at high altitude, but improved oxygen availability to tissues not until the second day of exposure 9.
- An earlier study published in 1992 found that acetazolamide was a useful prophylactic for acute mountain sickness, causing marked reduction in headache, nausea, vomiting, weakness, etc. 10.
Dosage Considerations
- The optimal dosage and timing of acetazolamide administration for high altitude prophylaxis are still debated, with different studies recommending different dosing regimens 6, 7, 8, 9.
- Higher doses of acetazolamide (500-750 mg/day) may be more effective for rapid ascents to high altitudes, but may also increase the risk of adverse effects 7.
- Lower doses of acetazolamide (125-250 mg/day) may be sufficient for slower ascents or for individuals who are more susceptible to adverse effects 8, 9.