Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial)

Abstract

Introduction-North American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied. Methods-We conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group. Results-Seventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5À10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5À13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885À1.144). Side effects were similar between the groups. Conclusions-The reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness.

Influence of methazolamide on the human control of breathing: A comparison to acetazolamide

“…A meta‐analysis on effective AZ doses in AMS prophylaxis published in 2012 showed that doses of 750, 500 and 250 mg day −1 were all effective in preventing AMS (Low, Avery, Gupta, Schedlbauer, & Grocott, ). According to a recent report, even lower doses (125 and 62.5 mg day −1 ) reduced the incidence of AMS (McIntosh et al., ). It is likely, therefore, that we used a higher AZ dose than necessary, although 250 mg three times daily is not unusual in clinical practice (Adamson & Swenson, ) and in AMS prophylaxis (Kayser et al., ).…”

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update

“…Although doses up to 750 mg daily are effective at preventing AMS compared to placebo, they are associated with more frequent and/or pronounced side effects, do not convey greater efficacy, and are not recommended for prevention. A recent, small study suggested that 62.5 mg every 12 h was noninferior to 125 mg every 12 h, 26 but further research with greater numbers of participants in different high altitude settings should be completed before a change in dose can be recommended. The pediatric dose of acetazolamide is 2.5 mg$kg -1 $dose -1 (maximum 125 mg$dose -1 ) every 12 h. 27 Recommendation.…”

Hæðarveiki og tengdir sjúkdómar

“…Nýleg rannsókn sýndi að lágur skammtur, 62,5 mg tvisvar á dag, hafði ekki síðri verkun en 125 mg af asetasólamíði tvisvar á dag. 53 Byrjað er að taka lyfið sólarhring fyrir haeðaraukningu og haett þegar aftur er komið niður fyrir 2500 m, eða ef staldrað er við í sömu haeð í meira en 4-5 sólarhringa 7 Ekki má gefa asetasólamíð þeim sem hafa ofnaemi fyrir súlfalyfjum vegna mögulegs krossofnaemis. 7 Til að ganga skugga um að lyfið þolist vel er maelt með að prófa lyfið við sjávarmál um tveimur vikum fyrir áaetlaða notkun.…”