Adverse effects of remdesivir, hydroxychloroquine, and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomized trials
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| Názov: | Adverse effects of remdesivir, hydroxychloroquine, and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomized trials |
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| Autori: | Izcovich, Ariel, Siemieniuk, Reed Alexander, Bartoszko, Jessica Julia, Ge, Long, Zeraatkar, Dena, Kum, Elena, Qasim, Anila, Khamis, Assem M, Rochwerg, Bram, Agoritsas, Thomas, Chu, Derek K, McLeod, Shelley L, Mustafa, Reem A, Vandvik, Per, Brignardello-Petersen, Romina |
| Zdroj: | BMJ Open BMJ Open, Vol 12, Iss 3 (2022) |
| Informácie o vydavateľovi: | Cold Spring Harbor Laboratory, 2020. |
| Rok vydania: | 2020 |
| Predmety: | Alanine / adverse effects, Adenosine Monophosphate / adverse effects, Alanine, Ritonavir, SARS-CoV-2, Ritonavir / adverse effects, Lopinavir / adverse effects, Adenosine Monophosphate / analogs & derivatives, Adenosine Monophosphate, Lopinavir, COVID-19 Drug Treatment, 3. Good health, Drug Combinations, Infectious Diseases, Alanine / analogs & derivatives, Medicine, Humans, Hydroxychloroquine / adverse effects, Hydroxychloroquine, Randomized Controlled Trials as Topic |
| Popis: | IntroductionIn an attempt to improve outcomes for patients with coronavirus disease 19 (COVID-19), several drugs, such as remdesivir, hydroxychloroquine (with or without azithromycin), and lopinavir/ritonavir, have been evaluated for treatment. While much attention focuses on potential benefits of these drugs, this must be weighed against their adverse effects.MethodsWe searched 32 databases in multiple languages from 1 December 2019 to 27 October 2020. We included randomized trials if they compared any of the drugs of interest to placebo or standard care, or against each other. A related world health organization (WHO) guideline panel selected the interventions to address and identified possible adverse effects that might be important to patients. Pairs of reviewers independently extracted data and assessed risk of bias. We analyzed data using a fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the GRADE approach.ResultsWe included 16 randomized trials which enrolled 8226 patients. Compared to standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference [RD] 8 fewer per 1000, 95% confidence interval (CI): 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI: 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of serious cardiac toxicity (RD 10 more per 1000, 95% CI: 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI: 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI: 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI: 23 more to 110 more) compared to standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI: 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI: 100 more to 210 more) compared to standard care or placebo.ConclusionHydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Remdesivir may have no effect on risk of acute kidney injury or cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| ISSN: | 2044-6055 |
| DOI: | 10.1101/2020.11.16.20232876 |
| DOI: | 10.1136/bmjopen-2020-048502 |
| Prístupová URL adresa: | https://www.medrxiv.org/content/medrxiv/early/2020/11/18/2020.11.16.20232876.full.pdf https://bmjopen.bmj.com/content/bmjopen/12/3/e048502.full.pdf https://pubmed.ncbi.nlm.nih.gov/35236729 https://doaj.org/article/b54a90ef65534deab17f82632cf7215b http://medrxiv.org/cgi/content/short/2020.11.16.20232876 https://www.medrxiv.org/content/10.1101/2020.11.16.20232876v1 https://europepmc.org/article/PPR/PPR239364 https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/en/ppmedrxiv-20232876 https://www.medrxiv.org/content/medrxiv/early/2020/11/18/2020.11.16.20232876.full.pdf |
| Rights: | CC BY NC ND CC BY NC URL: http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) . |
| Prístupové číslo: | edsair.doi.dedup.....65c9fe1b08314931ccf989f0bcc6f4d6 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | IntroductionIn an attempt to improve outcomes for patients with coronavirus disease 19 (COVID-19), several drugs, such as remdesivir, hydroxychloroquine (with or without azithromycin), and lopinavir/ritonavir, have been evaluated for treatment. While much attention focuses on potential benefits of these drugs, this must be weighed against their adverse effects.MethodsWe searched 32 databases in multiple languages from 1 December 2019 to 27 October 2020. We included randomized trials if they compared any of the drugs of interest to placebo or standard care, or against each other. A related world health organization (WHO) guideline panel selected the interventions to address and identified possible adverse effects that might be important to patients. Pairs of reviewers independently extracted data and assessed risk of bias. We analyzed data using a fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the GRADE approach.ResultsWe included 16 randomized trials which enrolled 8226 patients. Compared to standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference [RD] 8 fewer per 1000, 95% confidence interval (CI): 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI: 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of serious cardiac toxicity (RD 10 more per 1000, 95% CI: 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI: 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI: 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI: 23 more to 110 more) compared to standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI: 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI: 100 more to 210 more) compared to standard care or placebo.ConclusionHydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Remdesivir may have no effect on risk of acute kidney injury or cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19. |
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| ISSN: | 20446055 |
| DOI: | 10.1101/2020.11.16.20232876 |