Introduction Acetazolamide (AZM) is used for various conditions (eg, altitude sickness, sleep apnoea, glaucoma), but therapy is often limited by its side effect profile. Our objective was to estimate the risk of commonly reported side effects based on meta-analyses. We hypothesised that these risks are dose-dependent. Methods We queried MEDLINE/EMBASE (Medical Literature Analysis and Retrieval System Online/Excerpta Medica dataBASE) up until 04/10/2019, including any randomised placebo-controlled trial in which adults received oral AZM versus placebo reporting side effects. Eligibility assessment was performed by two independent reviewers. Data were abstracted by one reviewer who verified key entries at a second time point. For side effects reported by >3 studies a pooled effect estimate was calculated, and heterogeneity assessed via I2; for outcomes reported by >5 studies effect modification by total daily dose (EMbyTDD; <400 mg/d, 400–600 mg/d, >600 mg/d) was assessed via meta-regression. For pre-specified, primary outcomes (paraesthesias, taste disturbances, polyuria and fatigue) additional subgroup analyses were performed using demographics, intervention details, laboratory changes and risk of bias. Results We included 42 studies in the meta-analyses (Nsubjects=1274/1211 in AZM/placebo groups). AZM increased the risk of all primary outcomes (p<0.01, I2 ≤16% and low-to-moderate quality of evidence for all)—the numbers needed to harm (95% CI; nStudies) for each were: paraesthesias 2.3 (95% CI 2 to 2.7; n=39), dysgeusia 18 (95% CI 10 to 38, n=22), polyuria 17 (95% CI 9 to 49; n=22), fatigue 11 (95% CI 6 to 24; n=14). The risk for paraesthesias (beta=1.8 (95% CI 1.1 to 2.9); PEMbyTDD=0.01) and dysgeusia (beta=3.1 (95% CI 1.2 to 8.2); PEMbyTDD=0.02) increased with higher AZM doses; the risk of fatigue also increased with higher dose but non-significantly (beta=2.6 (95% CI 0.7 to 9.4); PEMbyTDD=0.14). Discussion This comprehensive meta-analysis of low-to-moderate quality evidence defines risk of common AZM side effects and corroborates dose dependence of some side effects. These results may inform clinical decision making and support efforts to establish the lowest effective dose of AZM for various conditions.

中文翻译：

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乙酰唑胺的副作用：评估总体风险和剂量依赖性的系统评价和荟萃分析。

简介乙酰唑胺（AZM）可用于各种疾病（例如高原反应，睡眠呼吸暂停，青光眼），但治疗通常受其副作用影响。我们的目标是根据荟萃分析评估通常报道的副作用的风险。我们假设这些风险是剂量依赖性的。方法我们查询直到2019年4月10日为止的MEDLINE / EMBASE（在线医学文献分析和检索系统/ Excerpta Medica数据库），包括任何成人接受口服AZM与安慰剂报告副作用的随机安慰剂对照试验。资格评估由两名独立审核者进行。一位审阅者提取了数据，该审阅者在第二个时间点验证了关键条目。对于> 3项研究报告的副作用，计算了合并的影响估计值，并通过I2评估了异质性；对于超过5项研究报告的结局，通过荟萃回归评估了每日总剂量（EMbyTDD； <400 mg / d，400–600 mg / d，> 600 mg / d）的效果改善。对于预先指定的主要结局（感觉异常，味觉障碍，多尿和疲劳），使用人口统计学，干预措施详细信息，实验室变化和偏倚风险进行其他亚组分析。结果我们在荟萃分析中纳入了42项研究（AZM /安慰剂组为Nsubjects = 1274/1211）。AZM增加了所有主要结局的风险（p <0.01，I2≤16％，证据质量中度至中度）-每种情况所需的伤害数字（95％CI； n研究）为：感觉异常2.3（95 ％CI 2至2.7; n = 39），味觉不良18（95％CI 10至38，n = 22），多尿症17（95％CI 9至49; n = 22），疲劳11（95％CI 6至24） ； n = 14）。感觉异常的风险（beta = 1.8（95％CI 1。1至2.9）；随着AZM剂量的增加，PEMbyTDD = 0.01）和味觉障碍（β= 3.1（95％CI 1.2至8.2）； PEMbyTDD = 0.02）增加；较高的剂量也会增加疲劳风险，但无统计学意义（β= 2.6（95％CI 0.7至9.4）； PEMbyTDD = 0.14）。讨论这种对中低质量证据的综合荟萃分析定义了常见AZM副作用的风险，并证实了某些副作用的剂量依赖性。这些结果可能会为临床决策提供依据，并为建立针对各种情况的最低AZM​​有效剂量提供支持。讨论这种对中低质量证据的综合荟萃分析定义了常见AZM副作用的风险，并证实了某些副作用的剂量依赖性。这些结果可能会为临床决策提供依据，并为建立针对各种情况的最低AZM​​有效剂量提供支持。讨论这种对中低质量证据的综合荟萃分析定义了常见AZM副作用的风险，并证实了某些副作用的剂量依赖性。这些结果可能会为临床决策提供依据，并为建立针对各种情况的最低AZM​​有效剂量提供支持。