Adverse effects of remdesivir, hydroxychloroquine, and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomized trials

Background: To summarize 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
randomized 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 GRADE
approach. Results: We included 16 randomized trials which enrolled 8226
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 to
standard care or placebo, low certainty evidence suggests that remdesivir
may not have an important effect on acute kidney injury or cognitive
dysfunction/delirium. Low certainty evidence suggests that
hydroxychloroquine may increase the risk of cardiac toxicity (and
cognitive dysfunction/delirium, 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 and nausea and/or vomiting compared to
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. Funding: This study was supported
by the Canadian Institutes of Health Research (grant: VR4-172738)
Registration: Not registered in PROSPERO, protocol available in the
supplementary material of BMJ 2020;370:m2980;
http://dx.doi.org/10.1136/bmj.m2980.