Medicinal Plants Research Center (NPPM), Post-graduation Program in Pharmacology, Federal University of Piauí, Teresina, PI, Brazil.
Biotechnology and Biodiversity Research Center (BIOTEC), Post-graduation Program in Biotechnology, Parnaíba Delta Federal University (UFDPar), Parnaíba, PI, Brazil.
Crit Rev Toxicol. 2024 Jul;54(6):345-358. doi: 10.1080/10408444.2024.2348169. Epub 2024 Jun 11.
During the COVID-19 pandemic, several drugs were repositioned and combined to quickly find a way to mitigate the effects of the infection. However, the adverse effects of these combinations on the gastrointestinal tract are unknown. We aimed investigate whether Hydroxychloroquine (HD), Azithromycin (AZ), and Ivermectin (IV) used in combination for the treatment of COVID-19, can lead to the development of gastrointestinal disorders. This is a systematic review and network meta-analysis conducted using Stata and Revman software, respectively. The protocol was registered with PROSPERO (CRD42023372802). A search of clinical trials in Cochrane Library databases, Embase, Web of Science, Lilacs, PubMed, Scopus and Clinicaltrials.gov conducted on November 26, 2023. The eligibility of the studies was assessed based on PICO criteria, including trials that compared different treatments and control group. The analysis of the quality of the evidence was carried out according to the GRADE. Six trials involving 1,686 COVID-19 patients were included. No trials on the association of HD or AZ with IV met the inclusion criteria, only studies on the association between HD and AZ were included. Nausea, vomiting, diarrhea, abdominal pain and increased transaminases were related. The symptoms of vomiting and nausea were evaluated through a network meta-analysis, while the symptom of abdominal pain was evaluated through a meta-analysis. No significant associations with these symptoms were observed for HD, AZ, or their combination, compared to control. Low heterogeneity and absence of inconsistency in indirect and direct comparisons were noted. Limitations included small sample sizes, varied drug dosages, and potential publication bias during the pandemic peak. This review unveils that there are no associations between gastrointestinal adverse effects and the combined treatment of HD with AZ in the management of COVID-19, as compared to either the use of a control group or the administration of the drugs individually, on the other hand, highlighting the very low or low certainty of evidence for the evaluated outcomes. To accurately conclude the absence of side effects, further high-quality randomized studies are needed.
在 COVID-19 大流行期间，几种药物被重新定位并联合使用，以迅速找到减轻感染影响的方法。然而，这些组合对胃肠道的不良反应尚不清楚。我们旨在研究羟氯喹（HD）、阿奇霉素（AZ）和伊维菌素（IV）联合用于治疗 COVID-19 是否会导致胃肠道疾病的发生。这是一项使用 Stata 和 Revman 软件分别进行的系统评价和网络荟萃分析。该方案已在 PROSPERO（CRD42023372802）上注册。于 2023 年 11 月 26 日在 Cochrane 图书馆数据库、Embase、Web of Science、Lilacs、PubMed、Scopus 和 Clinicaltrials.gov 中对临床试验进行了检索。根据 PICO 标准评估研究的入选标准，包括比较不同治疗方法和对照组的试验。根据 GRADE 对证据质量进行分析。共纳入 6 项涉及 1686 例 COVID-19 患者的试验。没有关于 HD 或 AZ 与 IV 关联的试验符合纳入标准，仅纳入了关于 HD 与 AZ 关联的研究。恶心、呕吐、腹泻、腹痛和转氨升高与这些药物有关。通过网络荟萃分析评估了呕吐和恶心症状，通过荟萃分析评估了腹痛症状。与对照组相比，HD、AZ 或它们的组合与这些症状均无显著相关性。间接和直接比较的异质性低且无不一致性。局限性包括样本量小、药物剂量不同以及大流行高峰期可能存在发表偏倚。本综述表明，与对照组或单独使用药物相比，在管理 COVID-19 方面，HD 联合 AZ 治疗与胃肠道不良事件之间没有关联，另一方面，对于评估结果，证据的确定性非常低或低。为了准确得出没有副作用的结论，需要进一步开展高质量的随机研究。
