Ivermectin and COVID-19: Why it’s promising

Doctors around the world has been reporting high success rates using an inexpensive anti-parasitic treatment for COVID-19. 

In April last year, a trial at Melbourne’s Monash University reported doses of ivermectin stopped or slowed the spread of Covid-19 infection in the lab environment. The researchers said the findings could not be immediately applied to humans but the drug still surged in popularity across Peru, Bolivia, Guatemala and other Latin American countries.

Another study published in June 2020 by Nature, ivermectin was found to have antiviral activity against a range of viruses including Avian influenza A, Porcine Reproductive and Respiratory Syndrome, HIV, and SARS-Cov-2.

The medical community is battling over whether ivermectin should be used to treat and prevent COVID-19. On one side are experts telling you that more research is needed before the treatment can be fully authorised. On the other, are experts telling you that the potential benefits outweigh the risk. Confused? 

Hopefully, this article can help you make sense of the options and to separate the facts from fiction.

NIH Recommendation on the Use of Ivermectin for the treatment of COVID-19

“The COVID-19 Treatment Guidelines Panel has determined that currently there are insufficient data to recommend either for or against the use of ivermectin for the treatment of 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 for the treatment of COVID-19.” 

The FLCCC has published a public statement with a list of responses to the above NIH statement:

"We are grateful that the Panel has upgraded their recommendation from “against use” to a neutral stance that neither promotes nor discourages use of ivermectin by doctors. A similar neutral stance applies to monoclonal antibodies and convalescent plasma, both of which are widely used in COVID-19 treatment in the U.S."..

NIH Summary Description of the Evidence Base

“Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory markers, shorter time to viral clearance, or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo.” 

FLCCC Response: We strongly object to suggesting that there is a clinical evidence of worsening disease with ivermectin use. The first three open label RCT’s (references 11–13) found no benefit with short duration of treatment (1–2 days) vs. early viral clearance when treatment was extended to five days. Only the observational study by Soto-Becerra et al. (references 14) reported contradictory findings of potential harm. This study consisted of a pharmacy database analysis which attempted to compare patient groups that received either hydroxychloroquine, azithromycin, or ivermectin (dosage and duration not reported) to those that received supportive care only. In each treatment group, a large number of early deaths occurred while none occurred in the control group, clearly indicating that the sicker and more imminently dying patients received some form of “experimental treatment.” If a study of this quality and design had instead somehow concluded a benefit for ivermectin, as evidence-based scientists and clinicians we would be among the first to rapidly dismiss it as biased or of limited interpretive power.

You can read the FLCC list of responses and conclusion at the FLCCC website.

Ivermectin Dosage in Humans for COVID-19 - FLCCC Protocol

For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated January 12, 2021):

• Ivermectin 0.2 mg/kg per dose. One dose daily - minimum 2 days, maximum 5 days.

Combined with:

• Vitamin D3 — 4000 IU/day. (Amazon)
• Vitamin C - 2,000 mg BID (twice daily) (Amazon)
• Quercetin 250 mg twice a day. (Amazon)
• Melatonin: 10 mg before bedtime (causes drowsiness). (Amazon)
• Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
• Aspirin 325 m/day unless contraindicated.
• FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to 
  the hospital if you get below 94%.

Ivermectin Dosage Chart for Humans by body weight for prophylaxis and treatment of COVID-19 (Credit: Rebelem.com)

Ivermectin Dosage in Humans for COVID-19 - AAPS Protocol

For early outpatient protocol (COVID-19 positive), the AAPS (American Association of Physicians and Surgeons) recommends:

• Ivermectin 0.2 - 0.6 mg/kg [6-36 mg] single oral dose given daily or every other day for 2-3 doses.

Ivermectin and COVID-19 Updates:

Feb 25, 2021: Drug used to treat lice and scabies drug could cut Covid deaths by up to 75%, research suggests, DailyMail reported.

Feb 25, 2021: Scabies and head lice drug could be 'global solution to the pandemic' says study; Mirror UK reported.

Jan 23, 2021: Researchers at Oxford University are planning the first, large high-quality trial of Ivermectin that has been credited with dramatically reducing Covid-19 deaths in the developing world. The PRINCIPLE trial is aiming to find a drug that works soon after virus symptoms appear in a patient, and one that is most effective during the primary stages of the illness, The Times reported.

Jan 19, 2021: A pilot study published in the Lancet on January 19, 2021 showed some promising results but the authors concluded that the study warrants further exploration under larger trials with clinical outcomes in patients with risk factors or more severe disease.

Jan 18, 2021: Updated version of Frequently Asked Questions on Ivermectin in COVID-19 by the FLCCC.

Jan 14, 2021: The National Institutes (NIH) has issued a new statement on the use of the anti-parasitic drug ivermectin for the treatment of COVID-19. Previously, it recommended against this treatment, but now states that its Panel “has determined that there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19.”

Jan 13, 2021: The BIRD meeting was convened by Dr. Tess Lawrie in order to present the findings from her rapid systematic review and meta-analysis of studies on the use of ivermectin to prevent and treat COVID-19. Dr. Lawrie presented evidence in the form of a DECIDE evidence-to-decision framework, a format used by the World Health Organization for the development of guidelines and recommendations in medical practice. Twenty experts from around the world and the UK attended the meeting, including 13 clinicians, and seven representatives from the public.

Dec 30, 2020: An essential updated review of COVID-19 early-treatment best practices was published. (abstract | PDF | HTML)

This international collaboration — comprised of physicians, like lead author Peter McCullough, MD, courageously treating patients despite the prevalence of “therapeutic nihilism” among government agencies like the NIH and FDA — outlines the urgency of, “prompt early initiation of sequenced multidrug therapy (SMDT) … to stem the tide of hospitalizations and death.”

The authors wrote: 

The early stage of viral replication provides a therapeutic window of tremendous opportunity to potentially reduce the risk of more severe sequelae in high risk patients. Precious time is squandered with a ‘wait and see’ approach … resulting in unnecessary hospitalization, morbidity, and death. … In newly diagnosed, high-risk, symptomatic patients with COVID-19, SMDT has a reasonable chance of therapeutic gain with an acceptable benefit-to-risk profile.

Included in the paper is a “sequential multi-drug treatment algorithm” and summaries of the rationale and evidence for each component.

Dec 8, 2020: Appearing as a witness on Dec. 8, 2020, before the Senate Committee on Homeland Security and Governmental Affairs—which held a hearing on “Early Outpatient Treatment: An Essential Part of a COVID-19 Solution”— Dr. Pierre Kory, President of the Frontline COVID-19 Critical Care Alliance (FLCCC), called for the government to swiftly review the already expansive and still rapidly emerging medical evidence on Ivermectin.

Related Ivermectin and COVID-19 Scientific Publications:

• Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 by Kory et al., provisionally accepted on Frontiers in Pharmacology.
• A multi-centre randomised controlled study in Egypt (Elgazzar, Research Square) reported that the death rate was significantly lower in Ivermectin treated patients group (severe patients) vs non-Ivermectin group (2% vs 20%). 1,300 patients were included in this randomized controlled trial. 
• This randomized controlled trial out of Iran (Hashim, pre-print) used Ivermectin and Doxycycline in mild, moderate, and severe hospitalized COVID-19 patients. No patients in the mild and moderate COVID-19 category died and 18% of the severe patients perished taking this medication combo. In the control group, no mild-moderate patients died, but 27% of the severe COVID patients died. The patients who also got Ivermectin had a shorter recovery.
• A randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical trial at five hospitals (Iran) and 180 patients with mild to severe disease (Niaee, ResearchSquare, Nov 2020). Ivermectin as an adjunct reduced the rate of mortality, the duration of low oxygen saturation, and the duration of hospitalization.
• The ICON study in US, published in Chest, Oct 2020 reported that Ivermectin treatment was associated with lower death rate vs Control (13.3% vs 24.5%) during treatment of COVID-19, especially in patients with severe pulmonary involvement.
• A double-blinded randomised controlled study in Bangladesh (Mahmud et al) reported that the death rate was 0% (0/183) in the Ivermectin arm vs 1.67% (3/180) in the control arm in mild to moderate COVID-19 patients.
• The IDEA (Ivermectin, Dexamethasone, Enoxaparin and Aspirin) study from Argentina reported 1 death out of 167 patients studied. The patient that died was a severe COVID-19 patient that required ventilator support.
• The pre-AndroCoV trial from Brazil reported that early detection of COVID-19 followed by a pharmaceutical approach with different drug combinations (Azithromycin, Hydroxychloroquine, Nitazonide, Ivermectin) yielded irrefutable differences compared to non-treated controls in terms of clinical outcomes, ethically disallowing placebo-control randomized clinical trials in the early stage of COVID-19 due to the marked improvements.
• A retrospective study out of Bangladesh (Khan, Archivos de Bronconeumologia 2020). This retrospective study enrolled a total of 325 from April to June 2020. 248 adult COVID-19 patients were looked at in two groups, 115 received ivermectin plus standard care (SC), while 133 received only standard care (SC). This study showed that Ivermectin was efficient at rapidly clearing SARS-CoV-2 from nasal swabs (median 4 days). This was much shorter than in the COVID-19 patients receiving only SC (15 days) or receiving a combination of three antiviral drugs (7–12 days). In addition, fewer Ivermectin patients developed respiratory distress leading to ICU admission. In fact, with Ivermectin, there was a quick hospital discharge (median 9 days) in 114 out of 115 patients; the one remaining patient had been admitted with advanced disease.

Ivermectin Contraindications

Asthma: Patients with a history of severe asthma should receive ivermectin with caution. Occasionally, systemic ivermectin has been reported to worsen bronchial asthma.

Hepatic disease: Although not extensively studied, due to its extensive hepatic metabolism, ivermectin should be administered with caution in patients with significant hepatic disease.

Human immunodeficiency virus (HIV) infection, immunosuppression: In patients with immunosuppression (including those with human immunodeficiency virus (HIV) infection) treated for intestinal strongyloidiasis, repeated ivermectin courses may be necessary. Adequate and well-controlled clinical studies have not been conducted in such patients to determine the optimal dosing regimen. Several treatments (i.e., at 2 week intervals) may be required and a cure may not be achievable. Control of extra-intestinal strongyloidiasis in these patients is difficult, however, suppressive therapy (i.e., once per month) may be helpful.

Pregnancy: Data with oral ivermectin use during pregnancy are insufficient to inform a drug-associated risk. Systemic exposure from topical use of ivermectin is much lower than from oral use. Four published epidemiology studies evaluated the outcomes of a total of 744 women exposed to oral ivermectin in various stages of pregnancy. In the largest study, 397 women in the second trimester of pregnancy were treated open-label with single doses of ivermectin or ivermectin plus albendazole; there was no observed difference in pregnancy outcomes between treated and untreated populations. However, these studies cannot definitely establish or exclude the absence of drug-associated risk during pregnancy, because either the timing of the administration during gestation was not accurately ascertained or the administration only occurred during the second trimester. In animal embyrofetal development studies of oral ivermectin given during organogenesis, adverse developmental outcomes, including cleft palate, exencephaly, wavy ribs, and clubbed forepaws, occurred at or near doses that were maternally toxic. Pre-implantation loss and abortion were also noted.

Breast-feeding: After oral administration, ivermectin is excreted in human breast milk in low concentrations. Excretion in human breast milk after topical administration has not been evaluated. According to the manufacturer, treatment with oral ivermectin in mothers who are breast-feeding should only be undertaken when the risk of delayed treatment to the mother outweighs the possible risk to the newborn. Previous American Academy of Pediatrics (AAP) recommendations considered oral ivermectin to be usually compatible with breast-feeding. The amount of ivermectin present in human milk after topical application has not been studied; however, systemic exposure from topical ivermectin use is much lower than from oral use. According to the manufacturer, discontinue nursing or discontinue the topical cream, taking into account the importance of the drug to the mother. Women who are breast-feeding while using topical ivermectin should avoid accidental transfer of ivermectin to the breast area where it might be directly ingested while nursing.

Children, infants: The topical administration of ivermectin to infants and children should be under the direct supervision of an adult to prevent ingestion of the lotion.

Onchodermatitis: Patients with hyperreactive onchodermatitis (i.e., sowda) may be more likely than others to experience severe edema and worsening of onchodermatitis after ivermectin use.

Source: https://www.pdr.net/drug-summary/Sklice-ivermectin-2415

Ivermectin Meta-analysis of 42 studies

• 100% of the 42 studies to date report positive effects. Random effects meta-analysis for early treatment and pooled effects shows a reduction of 83%, RR 0.17 [0.11-0.28]. Prophylactic use shows a reduction of 89%, RR 0.11 [0.05-0.23]. Mortality results show 75% lower mortality, RR 0.25 [0.14-0.44] for all treatment delays, and 86% lower, RR 0.14 [0.03-0.62] for early treatment.
• 100% of the 21 Randomized Controlled Trials (RCTs) report positive effects, with an estimated reduction of 70%, RR 0.30 [0.19-0.49].

Source: ivmmeta.com

Conclusion

In conclusion, we suggest that you discuss with your doctor before taking any medication or supplement/s. Do not self-medicate. Do not buy any medication online. Reading this article or doing your own online research does not make you an instant expert. There's much more to it than what we have just covered. Unless you are a medical professional, you might misinterpret or may not fully understand the full consequences of a medical decision and the breadth and depth of the subject by just a few hours of online research.