Acetazolamide is a carbonic anhydrase inhibitor and is effective for conditions like glaucoma and acute mountain sickness, but frequently causes side effects such as paraesthesias, dysgeusia, polyuria, and fatigue. These adverse effects in turn limit compliance. Evidence suggests these side effects may be dose-dependent, prompting efforts to identify the lowest effective dose, the dose which shows similar efficacy to higher doses with fewer side effects.
This study analyzed data from RCTs to quantify the risk of side effects and assess dose dependency, finding that side effects vary with dose. The findings aim to support informed decision-making by balancing efficacy with tolerability. This review evaluated 53 studies to assess the side effects of acetazolamide across diverse conditions, with doses ranging from 125–4000 mg/day and treatment durations of 1–180 days. Acetazolamide increased the odds of primary side effects such as paraesthesias, dysgeusia, polyuria, and fatigue by 1.9–12.3 times, with dose dependency observed for some effects like paraesthesias and dysgeusia but not polyuria. Secondary side effects, including nausea, diarrhea, drowsiness, and tinnitus, were 2.3–4.7 times more likely, though dose dependence was not evident for these outcomes. Some rare adverse effects, like hypokalemia and metabolic acidosis, occurred primarily in specific settings, such as concurrent use of diuretics or critically ill patients. Results showed no significant publication bias, and highlighted the importance of monitoring renal function and side effects actively in acetazolamide trials.
This meta-analysis confirms that acetazolamide commonly causes dose-dependent side effects, including paraesthesias, dysgeusia, and fatigue, with paraesthesias being the most frequent. While these side effects may impact therapy compliance, they are less likely to lead to therapy discontinuation compared to fatigue and gastrointestinal symptoms, which are often non-dose-dependent and may improve with food intake.
The findings emphasize the importance of starting acetazolamide at the lowest effective dose to minimize side effects while maintaining efficacy. This is particularly relevant as different conditions may require varying doses of acetazolamide due to its dose-dependent pharmacodynamic effects. While paresthesias and dysgeusia can often be mitigated by dose reduction, gastrointestinal irritation may respond to administration with food.
