Union health ministry guidelines say the drug "may be" used for COVID-19 patients even as global agencies don't recommend
Scientists across the world are divided over the efficacy of Ivermectin, an antiparasitic that has made into India's Union health ministry’s guidelines for treating the novel coronavirus diseases (COVID-19) this year. It is being prescribed to a large share of patients in the country, although the Centre recommended it for those with mild symptoms or in home isolation.
Recently, the Goa government declared it will administer Ivermectin to its entire adult population as a prophylaxis (preventive drug) against COVID-19. The directive followed a meta-analysis published April 22, 2021 in the American Journal of Therapeutics that advocated using Ivermectin to prevent and treat COVID-19 globally, positioning it as a core medication for the infection.
The analysis was led by Front-Line COVID-19 Critical Care Alliance (FLCCC), a global alliance of critical care physicians, allied physicians and scholars. The paper concluded:
Meta-analyses based on 18 randomised controlled treatment trials of Ivermectin use for COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery and time to viral clearance. Results from numerous controlled prophylaxis trials have shown significantly reduced risks of contracting COVID-19 with the regular use of Ivermectin.
Ivermectin should be used to reduce morbidity and mortality associated with COVID-19 infection and to prevent the disease in high-risk individuals, said British Ivermectin Recommendation Development, a group of international experts, in February 2021.
Global agencies say no
Global agencies, however, did not recommend its use for treatment of COVID-19 or as a prophylaxis.
The World Health Organization (WHO) advised against using Ivermectin in patients with COVID-19, except in the case of a clinical trial, in its ‘Therapeutics and COVID-19: living guideline’ on March 31 this year.
The recommendation was informed by results from a living systematic review and analysis, pooling data from 16 randomised controlled trials with 2,407 COVID-19 patients.
The WHO guideline said:
When moving from evidence to the recommendation not to use Ivermectin except in the context of a clinical trial, the panel emphasised the large degree of uncertainty in the evidence on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement and other patient-important outcomes. There remains potential for harms with an increased risk of adverse events leading to study drug discontinuation.
The European Medicines Agency in March 2021 also warned against using Ivermectin for COVID-19 outside of clinical trials after analysing recent literature.
The US Food and Drug Administration, in a consumer update on March 21 this year, mentioned the use of Ivermectin has not been approved for use in treating or preventing COVID-19 in humans. The United States National Institutes of Health (NIH) said:
There is insufficient data for the COVID-19 Treatment Guidelines Panel to recommend either for or against the use of Ivermectin in treating COVID-19. Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin in the treatment of COVID-19.
Earlier on 4 Feb 2021, the pharmaceutical firm Merck, one of the companies that manufactures Ivermectin and had a patent on the drug till 1996, said there is no meaningful evidence for clinical efficacy of the medicine in COVID-19 patients.
Merck, in its statement also recognised that Ivermectin has significant interactions with Warfarin, an anti-coagulent often prescribed to COVID-19 patients. Taking them together can cause extreme blood thinning, leading to severe bleeding. “Thus, self-medication of both medications can lead to serious health complications.”
Indian guidelines recognise low evidence
The clinical management protocol for COVID-19 (version 5, July 2020) from the Union Ministry of Health and Family Welfare (MoHFW) did not talk about Ivermectin, but mentioned the use of hydroxychloroquine for management of mild and moderate diseases.
The All India Institute of Medical Sciences (AIIMS), however, said on September 2020: “Ivermectin has been found to be a potent inhibitor of SARS-CoV-2 replication in-vitro, but the doses required to achieve this effect in-vivo far exceeds the usual dosage. It is currently not recommended in the national guidelines but can be used in patients in whom HCQ is contraindicated.”
The second wave of COVID-19 infections in India became apparent in the first week of March 2021. By April, the daily addition of cases had surpassed last year’s peak.
It is during this time that MoHFW released the Clinical Guidance for Management of Adult CoVID-19 Patients developed jointly by the COVID-19 teams of AIIMS and Indian Council of Medical Research.
The document suggested Ivermectin “may be” given to those with mild cases and in home isolation as a therapy based on “low certainty of evidence”. A dose of 200 microgram per kilogram (mcg / kg) of body weight once a day for three-five days was suggested.
This was in line with the Union health ministry’s revised guidelines for Home Isolation of mild / asymptomatic COVID-19 cases, also released in April 2021.
However, none of the guidelines talked about the role of Ivermectin as a prophylactic medication. The central guidelines for COVID-19 treatment in children released around the same time didn’t mention Ivermectin therapy.
A consortium of senior expert clinicians, academics and methodologists from reputed institutions across the country, COVID-19 Management Guidelines India Group, also recommended against the drug. The group is led by the Christian Medical College, Vellore and the Clinical Infectious Diseases Society of India.
The experts highlighted the information gap in ensuring efficacy and safety of Ivermectin and said 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 infestations.”
There is a growing body of research globally on Ivermectin therapy for COVID-19.
A meta-analysis on prophylaxis against the infection, published in the bmj in April 2021, concluded that it is very uncertain if the drug alone or in combination with iota-carrageenan reduces the risk of SARS-CoV-2 infection and mortality. This was owing to “serious risk of bias and very serious imprecision”.
In India, a study by AIIMS, Bhubaneswar published in PlosOne February 2021 found two-dose Ivermectin prophylaxis at a dose of 300 mcg / kg with a gap of 72 hours was associated 73 per cent reduction of COVID-19 infection among healthcare workers for the following month. Due to its observational nature, however, the authors highlighted the need for further confirmation of study findings to strengthen the evidence before its large-scale use.
COVID-19 treatment guidelines from NIH, US tabulated selected clinical trial data along these lines. Findings from the trials indicate faster viral clearance and better clinical outcomes but one of the limitations was the small sample size.
Other limitations included covering only younger population or not including chronic disease population in study sample. These trials were conducted in different parts of the world such as Bangladesh, Pakistan, Spain, Iran, Egypt, Argentina, US and Peru.
(This is the second of a two-part series on global and national policies surrounding the use of Ivermectin for COVID-19)
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