COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Bhowmick S, Dang A, Vallish BN, et al. Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review. Drug Saf. 2021 Jun;44(6):635-644. doi: 10.1007/s40264-021-01066-y. Epub 2021 Apr 16.

INTRODUCTION AND OBJECTIVE: Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.

METHODS: After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar,, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design.

RESULTS: Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality.

CONCLUSIONS: Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.


Discipline / Specialty Area Score
Infectious Disease
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Hospital Doctor/Hospitalists rater

This is not very helpful in deciding one way or another. Doxi and ivermectin are used extensively, without good evidence, especially in India where the authors are based, so it may be that their opinion is influenced by local practice. Certainly, the conclusion is worded as such. As per the report, most RCTs had a high risk of bias and/or are not yet peer reviewed. The article is also difficult to read. It would have been good to have separately stated which outcome (if any) and in which group of patients, improved by these drugs, and whether this inference is based on a good quality RCT or otherwise.