Adverse events in people taking macrolide antibiotics versus placebo for any indication

Hansen, Malene Plejdrup; Scott, Anna Mae; McCullough, Amanda; Thorning, Sarah; Aronson, Jeffrey K; Beller, Elaine; Glasziou, Paul; Hoffmann, Tammy; Clark, Justin; Mar, Chris B Del

doi:10.1002/14651858.cd011825.pub2

Cited by 74 publications

(73 citation statements)

References 316 publications

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“…Secondly, including studies of all conditions increase the power to detect rare ADRs, and small but important increases in common symptoms. RCTs are usually underpowered and the unintended effects are expected to be the same, regardless of the indication for the intervention [56][57][58][59][60]. Thirdly, our review avoids the problem of "overlapping" when a multiple-indication review consists of systematic reviews that include some, but not all, of the same studies [56].…”

Section: Discussionmentioning

confidence: 99%

Adverse drug reactions associated with amitriptyline — protocol for a systematic multiple-indication review and meta-analysis

et al. 2020

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Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I 2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations.

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Section: Discussionmentioning

confidence: 99%

Adverse drug reactions associated with amitriptyline — protocol for a systematic multiple-indication review and meta-analysis

et al. 2020

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“…The findings regarding macrolide/azalide use are not surprising ( Table 1). The wellrecognized gastrointestinal upset associated with erythromycin likely contributed to its ADR rate (47.2/1,000,000 prescriptions) [6]. The higher reported ADR rate (99/1,000,000 prescriptions) observed for clarithromycin, however, is difficult to explain, although it is tempting to speculate that because clarithromycin is a more recently available macrolide as compared to erythromycin, a Yellow Card report is more likely to be submitted for clarithromycin.…”

Section: Discussionmentioning

confidence: 99%

Adverse drug reactions due to oral antibiotics prescribed in the community setting – England

Baddour

Dayer

2019

Infectious Diseases

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Background Oral antibiotic prescribing in the community setting is commonplace with ongoing efforts to optimize this practice. There are several concerns that relate to the practice and include antibiotic cost, development of bacterial resistance to these agents, and associated adverse drug events (ADR). We therefore performed an analysis of ADR associated with oral antibiotic prescriptions in community care (non-hospital) settings in England with the goal of determining both ADR reporting rates and severity due to oral antibiotics. Methods Data for all oral antibiotic use in the primary care settings in England and the National Yellow Card Interactive Drug Analysis Profile were both abstracted for 2010 through 2017. Results Overall, there were 320,599,292 prescriptions issued for oral antibiotics during the eight-year survey. Although the overall ADR rate was relatively low, 58/1,000,000, the reported serious (63.6%) and fatal (1.21%) rates were striking. Conclusions Continued monitoring of ADR rates due to oral antibiotic prescribing in the community setting is warranted, considering the prevalence of serious/fatal reports identified during the eight-year study period in the Yellow Card profile. These data should be useful in developing strategies in securing optimal prescribing practices.

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“…A Cochrane review has also concluded that there are beneficial effects of AZM in patients with bronchiectasis (114). The drawbacks are the potential risk of the development of resistance against AZM and adverse events, such as arrhythmias, diarrhea, and arthralgia (115).…”

Section: Antibiotics and Effects On Host Immunitymentioning

confidence: 99%

Host Directed Therapy Against Infection by Boosting Innate Immunity

et al. 2020

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Adverse events in people taking macrolide antibiotics versus placebo for any indication

Cited by 74 publications

References 316 publications

Adverse drug reactions associated with amitriptyline — protocol for a systematic multiple-indication review and meta-analysis

Adverse drug reactions associated with amitriptyline — protocol for a systematic multiple-indication review and meta-analysis

Adverse drug reactions due to oral antibiotics prescribed in the community setting – England

Host Directed Therapy Against Infection by Boosting Innate Immunity

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