This recommendation applies to acute COVID-19 in adults. Some of our recommendations vary according to the severity of COVID-19 illness. Definitions of the categories are based on the World Health Organization (WHO) criteria and can be viewed by clicking the plus (+) signs below.

RECOMMENDATION:  We recommend against using Ivermectin for treatment of patients with any severity of COVID-19 (strong recommendation). It has no benefit in reducing mortality, progression to mechanical ventilation and time to negative PCR and does not increase adverse effects.


We do not recommend use of Ivermectin for treating COVID 19 illness (Strong recommendation)

Definition of mild:

  • Symptomatic (any acute COVID-19 related symptoms)
  • AND respiratory rate <24/min
  • WITHOUT pneumonia or hypoxia

Definition of moderate illness:

  • Pneumonia (clinical or radiological) OR hypoxia (SpO2 <94% in adults with no underlying lung disease)
  • AND respiratory rate ≤30/min
  • AND SpO2 ≥90% on room air

Definition of Severe illness

Pneumonia with ANY ONE of the following:

  • severe respiratory distress or respiratory rate >30/min
  • SpO2 <90% on room air
  • NO invasive or non-invasive respiratory support needed

Definition of critical:

  •  Requirement for high-level respiratory support: noninvasive ventilation, high-flow oxygen (≥20 litres per minute) or invasive mechanical ventilation
  • OR acute respiratory distress syndrome (PaO2/FiO2 ratio of <300)
  • OR sepsis
  • OR shock

The evidence from 20 randomized controlled trials (1–20), with 4140 participants suggests that Ivermectin does not improve mortality [RR 0.65, 95% CI 0.39, 1.09], progression to mechanical ventilation [RR 0.74, 95% CI 0.53, 1.04] or viral clearance in patients by day 7 with COVID-19 infection [RR 1.31, 95% I 0.95, 1.81]. At the doses used in these trials (median dose is 12 mg once daily orally) it does not have any major adverse events [RR 1.00, 95% CI 0.60, 1.67]. Multiple studies on Ivermectin in Covid-19 have been methodologically unsound with many retracted from peer reviewed literature, further clouding the data. (21,22) A stratified analysis of all-cause mortality in studies with low risk of bias showed no benefit with Ivermectin [RR 0.85, 95% CI 0.48, 1.50]

Currently, its use may distract from use of other therapies for which there is better evidence. Indiscriminate use might also reduce its availability for other conditions where its benefit is established, such as parasitic infections. Taking this into account, we recommend against use of ivermectin outside of a randomized controlled trial.

Evidence summary

Date of latest search: 07 June 2022.

Date of completion of Summary of findings table: 29th August 2022

Evidence synthesis team:  Harshdeep Acharya, Audrin Lenin, Jane Miracline John, Sherly Shulamite, Jisha Sara, Richard Kirubakaran, Priscilla Rupali and Bhagteshwar Singh.

Valuable assistance with performing the evidence synthesis was provided by the author team of an ongoing Cochrane systematic review: Maria Popp, Miriam Stegemann, Maria-Inti Metzendorf, Peter Kranke, Patrick Meybohm, Nicole Skoetz and Stephanie Weibel (23).

Summary of findings table


a.  Downgraded by one level for serious imprecision, due to small absolute number of events, and CIs include important potential benefit and important potential harm.

b.  Downgraded by one level for serious risk of bias. Due to Galan 2021 and Niaee 2021 having high risk of bias, and Gonzalez 2021 , Ravikirti 2021 , Abd Elsalam and Shahbaznejad 2021 having some concerns for risk of bias.

c.  Downgraded by one level for serious risk of bias, due to Abd Elsalam , Galan 2021, Ravikirti 2021Shahbaznejad and I-tech trial having some concerns for risk of bias.

d.  Downgraded by two levels for very serious risk of bias, due to Ahmed 2020 and Bukhari 2021 having high risk of bias and Bieber having some concerns for risk of bias for this outcome.

e.  Downgraded by one level for serious inconsistency, due to substantial heterogeneity (I-squared=64%) and visually some trials having point effect estimates very far from those of other trials.

f.  Downgraded by one level for serious imprecision, due to CIs overlapping no effect and inability to exclude important benefit.

g.  Downgraded by one level for serious risk of bias., due to Chaccour 2021, Chachar 2021, Rocha et. al etc having high risk of bias (accounts for 15% weightage).

h.  Downgraded by one level for serious imprecision, due to CIs overlapping including important potential benefit and important potential harm.

i.  Downgraded by one level for serious risk of bias, due to Gonzalez 2021 having high risk of bias

j.  Downgraded by one level for serious imprecision, due to CIs including important potential benefit and important potential harm.


Ivermectin has been shown to inhibit the replication of SARS CoV2 in vitro; it binds and destabilises the viral protein and prevents it from entering the nucleus (24). However, the drug dosages used in these laboratory studies far exceed those that have been used for other conditions (25). Drug doses and levels required to achieve therapeutic effects in COVID-19 infection in humans based on these studies may be safe, but this has not been studied in clinical trials (26). An additional potential effect may be in modulating the immune system, though this is yet to be studied thoroughly in humans (27).

Although Ivermectin is generally well tolerated, adverse effects like dizziness, tachycardia, postural hypotension, diarrhoea, arthralgia, facial and peripheral oedema have been reported even with single doses as used in parasitic diseases (28). Encephalopathy with permanent disability has been reported when ivermectin has been used in the treatment of onchocerciasis or other parasitic diseases (28). It is predominantly metabolized in the liver (CYP3A4), which may lead to drug-drug interactions.

Due to lack of conclusive evidence from trials, World Health Organization recommends use of ivermectin only in clinical trials (29). Use continues widely, including self-medication, especially in low- and middle-income countries due to easy availability and low cost of the drug (30). Multiple trials on Ivermectin on covid-19 were retracted due to questionable methodology and lack of reliable data. (21,22)

This review aims to provide a summary of the available evidence from randomised clinical trials of ivermectin for treatment of acute COVID-19, for any dose or duration, so the Expert Working Group can provide a recommendation to guide clinicians and researchers regarding the appropriate use of this drug.


We used Cochrane rapid review methods. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Epistemonikos, and the COVID‐19‐specific resource www.covid‐nma.com, for studies of any publication status and in any language published from March 2020 up to 07th June 2022. We also reviewed reference lists of systematic reviews and included studies. We contacted researchers to identify unpublished and ongoing studies.

We included randomized controlled trials (RCTs) testing ivermectin treatment of any dose or duration in people with acute COVID‐19, whether suspected or confirmed. Trials were included if the intervention arm did not combine ivermectin with another experimental drug, and if the comparator arm did not include ivermectin (this could involve use of placebo, standard care, or other potentially active drugs). We excluded trials that did not report any outcomes that could provide usable data for the review, those which were quasi-randomized and those lacking a comparator arm.

We planned to extract data for the following outcomes, pre-defined by the Expert Working Group:

  • Critical (primary for this review):
    • Mortality (all-cause) – at 28-30 days, or in-hospital
    • Progression to:
      - Oxygen therapy
      - Ventilation: non-invasive or invasive
      - Critical or Intensive care (any reason)
    • Duration of hospitalization
    • Need for hospitalization (for out-patients)
    • Adverse events: all and serious
  • Important (secondary):
    • Time to clinical improvement
    • Time to negative PCR for SARS-CoV-2
    • Negative PCR for SARS-CoV-2 by day 7 post-enrolment
    • Complications of COVID-19:
      - Thrombotic events
      - Pulmonary function/fibrosis
      - Long covid/ post-covid sequalae
      - Secondary infections

Two reviewers independently assessed eligibility of search results. One reviewer extracted data from each included study and assessed risk of bias using the Cochrane Risk of bias (RoB) v2.0 tool. Data and RoB assessments were checked against a Cochrane systematic review team’s extractions and assessments (we used a consensus approach). In case of any discrepancies, the whole RoB assessment was scrutinised by the whole team for this review, to reach consensus.

We used RevMan 5.4 to perform meta‐analysis using a random‐effects model for outcomes where pooling of effect estimates was appropriate. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs).  We planned to explore heterogeneity in the effect on mortality using subgroup analysis comparing between trials, based on COVID-19 illness severity of participants included and risk of bias. We used the I2 statistic to measure residual heterogeneity. We used GRADE methodology to assess the certainty in the evidence and documented this in a ‘Summary of findings’ table using GradeProGDT.


We included 20 trials involving 4140 participants, all of whom were adults, and 2122 of whom received ivermectin (1–20). Of these 11 studies are included in the previous recommendation and 9 new studies were added to update the evidence (21,22) While updating the evidence, we excluded 1 study (22) which was present in the previous analysis as it was retracted due to unreliable methodology. There were two trials each from, India, Iran, Pakistan, Brazil, and Mexico; one trial each was reported from Bangladesh, Colombia, Nigeria, Egypt, Israel, Italy, Argentina, Spain, Thailand, and Malaysia. Eleven were in hospitalized patients, four recruited out-patients only, one recruited both, and three did not report care setting. Disease severity, prevalence of comorbidities, and use of co‐interventions varied substantially between trials. The ‘Summary of characteristics of included trials’ table provides further details about the trials.

We found potential risks of bias across all domains; 12 of the 20 trials were at high risk of bias overall for at least one outcome. Risk of bias for each domain per trial is displayed alongside the Forest plots below. Studies excluded at full-text review are listed in the References section, with the reason provided in brackets (21,22,31–40).

The following comparisons were investigated in the trials. We compared outcomes for arms randomised to ivermectin vs. outcomes in arms with placebo, standard care, or agents considered inactive or ineffective against COVID-19. Where multiple arms contained ivermectin without another experimental agent, we combined results in those arms into a single ivermectin arm, but we did not double-count controls. Where another experimental agent undergoing investigation was combined with ivermectin, that trial arm was excluded from the analysis (e.g., doxycycline).

  • Ten trials (3–5,8,9,11,14,17,18,20) compared ivermectin vs. placebo (2358 participants)
  • Six [18;22-23;25-26;29] compared ivermectin vs. standard care (1244 participants)
  • One (1) compared ivermectin vs. placebo vs. a combination of ivermectin & doxycycline in three arms (72 participants; 24 participants in ivermectin & doxycycline arm excluded)
  • One (5) compared ivermectin vs. placebo vs. hydroxychloroquine in three arms (106 participants)
  • One (2) compared ivermectin vs. lopinavir/ritonavir (62 participants)
  • One (4) compared ivermectin vs. chloroquine or hydroxychloroquine (168 participants)

All-Cause-Mortality: Low certainty evidence from 9 RCTs (6,8,10,12,15,19,20) with 3052 participants shows that ivermectin may result in little to no difference in mortality [RR 0.65, 95%CI 0.39,1.09]. As the studies have some concerns and high risk of biases, a stratified analysis of the data was done based on ‘Risk of bias’. The trials (8,20) with Low risk of bias showed no difference in mortality in patients receiving Ivermectin vs no Ivermectin [RR 0.85, 95%CI 0.48,1.50]

Progression to mechanical ventilation: Low certainty evidence from 8 trials (6,11,12,15,16) with 3263 participants showed that Ivermectin may have little to no effect in the progression to mechanical ventilation [RR 0.74, 95%CI 0.53,1.04]. 5 of the 8 included studies have some concerns.

Negative PCR by day 7: Very low certainty evidence from 7 trials (1,3,11,13,17,20) with 828 participants for viral clearance at day 7 [RR 1.31, 95%CI 0.95,1.81] gives no impression of Ivermectin’s effect on viral clearance at Day 7. Of the 7 trials, 3 of them where of High Risk of bias, 3 of them had some concerns and only 1 trial with low risk of bias and had only 19% weightage. (Look at the forest plot).

Adverse events: Low certainty evidence from 10 RCTs (4,5,8,9,13,14,16,18–20) with 3187 participants shows that Ivermectin results in no significant adverse events RR 1.00, [95%CI 0.79,1.25].

Serious adverse events: Low certainty evidence from 4 RCTs (7,8,19,20) with 2352 participants shows that Ivermectin results in no significant serious adverse events [RR 1.00, 95%CI 0.60,1.67].

One trial reported a higher risk of discontinuation of ivermectin vs. placebo due to an adverse event (RR 2.97; 95% CI 1.10 to 8.02; 1 trial (8); 398 participants).

95% confidence intervals for pooled effect estimates for all of the following outcomes not included in the summary of findings table included potential benefit and potential harm from ivermectin: need for critical or intensive care (2 trials (6,11); 283 participants); discharge from hospital by day 10 post-enrolment (1 trial (11); 115 participants); deterioration by 2 points on 8-point clinical ordinal scale (1 trial (8); 398 participants); lack of fever on day 7 (1 trial (1); 36 participants); lack of symptoms on day 7 (1 trial (5); 50 participants); and thrombotic events (1 trial (7); 106 participants). We were unable to pool data for time to clinical improvement as they were not reported in a way that was amenable to meta-analysis (3 trials (4,8,9); 149 participants).

No comparative data could be extracted for risk of progression to oxygen therapy; need for hospitalisation in outpatients; or post-acute COVID-19 pulmonary function/fibrosis or other sequelae; or secondary infections.

Lack of uniform criteria for COVID-19 severity, substantial overlap, and lack of clear reporting of severity in the included trials prevented a meaningful subgroup analysis by severity.

Furthermore, a lack of within trial comparison prevented subgroup analysis by age, duration of symptoms or dose of ivermectin. In addition, data of safety and efficacy in specific subgroups such as pregnancy, children, liver, and kidney disease were not available in the trials included in the rapid review.

Summary of characteristics of included trials

CQ: Chloroquine; ECOG: Eastern Cooperative Oncology Group score; HCQ: Hydroxychloroquine; Lpv/Rtn: Lopinavir/Ritonavir; NEWS: National early warning score; RCT: Randomized control trial; RTPCR: Reverse transcription polymerase chain reaction; SoC: Standard of care

Forest Plot

1.  Mortality, stratified by risk of bias

2.  Progression to mechanical ventilation

3.  Negative PCR for SARS-CoV-2 by day 7

4.  Adverse events

5.  Serious adverse events

Evidence to decision

The methodology group for the evidence updating met on 29th March 2022 and the Voting for the recommendation by the Antiviral Expert working group completed on 09th May 2022 to consider Ivermectin as a treatment for COVID-19. A summary and then more detailed explanations of their judgements follow.


There is some evidence in the literature regarding use of ivermectin for treatment of COVID-19, but reports of trials and reviews are conflicting. Given current demand for effective treatments, examination of the evidence and a recommendation based on this is a priority. The PICO question now applies for all patients with COVID-19 (initial PICO was for hospitalised patients).

Desirable effects

The 95% CI for the pooled effect estimates for mortality, progression to mechanical ventilation and negative PCR at day 7 included the line of no difference (i.e.1); and the certainty of the evidence was low. This means that the desirable effects of ivermectin are not different from placebo or soc.

Undesirable effects

All 95% CI for the pooled effect estimates for adverse events and serious adverse events included the line of no difference (i.e.1); indicating that we do not know if adverse events are any different with ivermectin compared to placebo or the interventions compared in the trials.  This drug has been widely used and adverse effects at the dose used have not been reported commonly.

The group felt that in a patient with COVID, drug interactions are possible. For example, ivermectin can increase the concentration of warfarin, and one group member reported a case where a patient with COVID disease who was on warfarin and given ivermectin developed severe bleeding. The group also cautioned that use with dexamethasone can reduce ivermectin concentrations.

There is also the indirect risk of harm from relying on this treatment and not using treatments with better evidence, such as good supportive care.

Certainty of evidence

Using GRADE methods, the team rated the certainty of evidence as low for all outcomes in the Summary of findings table. The group agreed.


The review included critical and important outcomes. Results were not reported for all, but results were pooled, and GRADE applied for four critical outcomes and one important outcome including death and adverse events.

Balance of effects

Since the certainty of evidence was low for desirable and undesirable effects of ivermectin, this means we do not know if ivermectin has an overall desirable effect compared to an undesirable effect when given to people with COVID disease.

Ivermectin used to be a part of the clinical protocol recommended by the Ministry of Health & Family Welfare for mild COVID-19 disease but is no longer recommended (41). The group discussed whether an intervention should be given if there is no observed benefit, as there is a risk to giving any intervention (see the section on Undesirable effects above).

Resources required

Cost of a dose, or a course as used in trials (up to 7 days of usual daily dose of up to 12mg) is low.

Certainty of evidence of required resources

Ivermectin is a low-cost treatment widely used in low- and middle-income settings for other conditions. We did not use published evidence on costs for this judgement, as ivermectin has been used extensively by the members of the expert working group for other conditions.

Cost effectiveness

None of the included trials assessed cost-effectiveness.


There is not enough information to make this judgement.


The group felt that many well-informed clinicians and patients may not accept an intervention for which the evidence for beneficial and adverse events were uncertain. However, in the context of a surge with few evidence-based therapeutic options, other clinicians and patients would feel a relatively safe, cheap oral drug might be acceptable in the absence of evidence for benefit. The group finally judged that ivermectin would probably be accepted, under such circumstances.


Evidence about feasibility was not specifically examined for COVID-19, but the group is aware of reports of mass-drug administration of ivermectin for other indications.

The group noted that it would be feasible to administer ivermectin in India for COVID-19 if it was found effective. However, we do not have data right now to suggest this. The group felt a recommendation for use would only detract from other interventions which have reported an unequivocal benefit.

Implementation considerations

Ivermectin is widely available, relatively inexpensive and has a low risk of adverse drug reactions. It may be used citing that lack of evidence of benefit is not evidence of lack of benefit. However, there are likely indirect harms. Its use may lead to a false sense of security. This could hamper close monitoring, and cause delay in the use of other interventions for which better evidence of benefit exists.

This recommendation is an update to the previous recommendation which was a conditional recommendation against the use of ivermectin in COVID-19.

Subgroup considerations

Our strong recommendation against use of ivermectin applies to all subgroups of patients with COVID-19.

Monitoring and evaluation

This strong recommendation against use of ivermectin may be revisited as evidence emerges. In addition to evidence of benefit, with its widespread use in India, there may be additional real-world reports regarding undesirable effects, which the group will monitor.

Research priorities

Further evidence for the use of Ivermectin in the treatment of COVID-19 needs to be generated from well-conducted randomized double-blind placebo-controlled trials which are adequately powered and have a low risk of bias. Utility in pre-specified patient sub-groups like mild, moderate, or severe infection, special populations (immunosuppressed, pregnant, children, comorbid conditions), and various phases of the illness will also need to be addressed. Safety of the dose required to achieve an antiviral/immunomodulatory effect also needs to be evaluated.

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Covid Management Guidelines India Group - Anti-viral Working Group. Ivermectin. Covid Guidelines India; Published online on Oct 06th, 2022; URL:  https://indiacovidguidelines.org/ivermectin-2/ (date<>).

Ivermectin – (Previous Recommendations)