A Systematic Review to Assess Assessing Side Effects of Acetazolamide

Abstract

Background:
Acetazolamide (AZM), a carbonic anhydrase inhibitor, is widely used for conditions such as glaucoma, acute mountain sickness (AMS), and idiopathic intracranial hypertension. While effective, AZM’s use is often limited by frequent side effects, including paraesthesia, dysgeusia, polyuria, and fatigue, which may be dose-dependent. Previous studies have provided limited quantitative data, necessitating a systematic assessment of the overall risk and dose dependence of AZM’s adverse effects.
Methods:
We conducted a systematic review of randomized controlled trials (RCTs) comparing oral AZM to placebo in adults. Studies reporting side effects were included, while those involving non-adults, hemodialysis patients, non-oral AZM formulations, or combined treatments were excluded. Primary outcomes included paraesthesia, dysgeusia, polyuria, and fatigue. Data were extracted and analyzed using the Mantel-Haenszel method,
Results:
A total of 35 studies met the inclusion criteria, encompassing diverse AZM dosages (125–4000 mg/day) and treatment durations (1–180 days). AZM significantly increased the risk of paraesthesia (OR: 6.5, NNTH: 2.3), dysgeusia (OR: 3.2, NNTH: 18), polyuria (OR: 2.7), and fatigue (OR: 2.3).. Secondary side effects, such as nausea, diarrhea, and drowsiness, were also significantly associated with AZM. Sensitivity analyses confirmed robustness, and publication bias was not detected.
Conclusion:
AZM use is associated with a significant and dose-dependent increase in common side effects, particularly paraesthesia, dysgeusia, and fatigue. These findings underscore the importance of balancing efficacy with tolerability by optimizing AZM dosing. Clinicians should consider individual patient factors, such as renal function and body weight, when prescribing AZM to minimize adverse effects and improve adherence.