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Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials.
BMJ Open. 2022 03 02; 12(3):e048502.BO

Abstract

BACKGROUND

To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19.

METHODS

We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach.

RESULTS

We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with 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% 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 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 with 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 with standard care or placebo.

DISCUSSION

Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.

Links

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Authors+Show Affiliations

Izcovich A
Department of Internal Medicine, Hospital Alemán de Buenos Aires, Buenos Aires, Argentina ariel.izcovich@gmail.com.
Siemieniuk RA
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Bartoszko JJ
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Ge L
Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.
Zeraatkar D
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Kum E
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Qasim A
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Khamis AM
Hull York Medical School, University of Hull, York, UK.
Rochwerg B
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Agoritsas T
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada. Division of General Internal Medicine & Division of Epidemiology, University Hospitals of Geneva, Geneva, Switzerland.
Chu DK
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada. Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
McLeod SL
Schwartz/Reisman Emergency Medicine Institute, Sinai Health System, Toronto, Ontario, Canada. Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
Mustafa RA
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada. Department of Medicine, University of Kansas Medical Center, Kansas City, Missouri, USA.
Vandvik P
MAGIC Evidence Ecosystem Foundation, Oslo, Norway.
Brignardello-Petersen R
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.

MeSH

Adenosine MonophosphateAlanineDrug CombinationsHumansHydroxychloroquineLopinavirRandomized Controlled Trials as TopicRitonavirSARS-CoV-2COVID-19 Drug Treatment

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

35236729

Citation

Izcovich, Ariel, et al. "Adverse Effects of Remdesivir, Hydroxychloroquine and Lopinavir/ritonavir when Used for COVID-19: Systematic Review and Meta-analysis of Randomised Trials." BMJ Open, vol. 12, no. 3, 2022, pp. e048502.
Izcovich A, Siemieniuk RA, Bartoszko JJ, et al. Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. BMJ Open. 2022;12(3):e048502.
Izcovich, A., Siemieniuk, R. A., Bartoszko, J. J., Ge, L., Zeraatkar, D., Kum, E., Qasim, A., Khamis, A. M., Rochwerg, B., Agoritsas, T., Chu, D. K., McLeod, S. L., Mustafa, R. A., Vandvik, P., & Brignardello-Petersen, R. (2022). Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. BMJ Open, 12(3), e048502. https://doi.org/10.1136/bmjopen-2020-048502
Izcovich A, et al. Adverse Effects of Remdesivir, Hydroxychloroquine and Lopinavir/ritonavir when Used for COVID-19: Systematic Review and Meta-analysis of Randomised Trials. BMJ Open. 2022 03 2;12(3):e048502. PubMed PMID: 35236729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. AU - Izcovich,Ariel, AU - Siemieniuk,Reed Alexander, AU - Bartoszko,Jessica Julia, AU - Ge,Long, AU - Zeraatkar,Dena, AU - Kum,Elena, AU - Qasim,Anila, AU - Khamis,Assem M, AU - Rochwerg,Bram, AU - Agoritsas,Thomas, AU - Chu,Derek K, AU - McLeod,Shelley L, AU - Mustafa,Reem A, AU - Vandvik,Per, AU - Brignardello-Petersen,Romina, Y1 - 2022/03/02/ PY - 2022/3/3/entrez PY - 2022/3/4/pubmed PY - 2022/3/9/medline KW - COVID-19 KW - adverse events KW - infectious diseases SP - e048502 EP - e048502 JF - BMJ open JO - BMJ Open VL - 12 IS - 3 N2 - BACKGROUND: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. METHODS: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach. RESULTS: We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with 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% 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 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 with 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 with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19. SN - 2044-6055 UR - https://www.unboundmedicine.com/medline/citation/35236729/Adverse_effects_of_remdesivir_hydroxychloroquine_and_lopinavir/ritonavir_when_used_for_COVID_19:_systematic_review_and_meta_analysis_of_randomised_trials_ DB - PRIME DP - Unbound Medicine ER -