Clinical Landscape - Report On Ivermectin 2020-05-01

2020
Clinical Landscape
Report on Ivermectin
Potential candidate for Prophylaxis &
treatment
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5/1/2020
Clinical Landscape report on Ivermectin for Covid19 1
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Preface
It’s been months and still the whole world is trying desperately to invent a new drug or to
repurpose an old one. In this scenario, the key to drug discovery for this deadly virus is
intelligence on all such treatments and vaccines. While it will take 12-18 months for vaccines to
come, the best bet we have to save the world is to find an existing drug that has a proven
safety profile and for treating COVID-19 patients.
The COVID-19 pandemics has fueled research efforts towards repurposing existing drugs as
possible antiviral agents, whereby the therapeutic strategies have been largely based on pre-
existing data for the preceding coronavirus outbreaks TORS and MERS1-3. The drug regulatory
agencies, health authorities, key opinion leaders and policy decision makers have been
significantly strained by the dilemma of evidence-based medicine and good clinical practice
versus the prompt need for safe and effective treatment. Unfortunately, we have been
witnessing huge public and political pressure for legitimation of drug-repurposing and off-label
use worldwide, which nonetheless could be regarded as an acceptable compromise, pending
the emergency of the current situation, but only in case of drugs with well-defined safety
profiles and at least some clinical evidence in COVID-19.
The report presents one such existing drug Ivermectin, as a potential preventive medication to
reduce viral load of COVID-19. It is also known as ’wonder drug’ like Penicillin and Aspirin, is an
FDA-approved anti-parasitic previously known to have broad-spectrum anti-viral activity in
vitro and most importantly is an inhibitor of the causative virus (SARS-CoV-2). The only way to
break the chain and bring back the economy on track is to find an already proven FDA
approved drug which has been successfully mass administered in past with exceptional safety
profile and most importantly is affordable for Indians unlike super expensive drugs, like
Remdesivir, which will cost approximately INR 50,000 for a 5 days’ course (even for a generic
version). One example of its efficacy is from the results of trials. Its use has shown a ~5000-fold
decrease in the viral load within 48 hours. Ivermectin has also reduced mortality rates in
hospitalized COVID-19 Patients in a Cohort Clinical Study Conducted in South Florida.
The proposed generic drug reduces efforts and costs for developing a new vaccine. This report
covers the major research conducted globally for determining efficacy of Ivermectin for COVID
patients. The report provides exhaustive details on safety profile of, its adverse events recorded
in history, its past clinical trial records and combinations, record of brand names under which it
is sold in India, pros and cons on the use of Ivermectin, etc.
Perhaps more than any other drug, Ivermectin is a drug for the world’s poor. For most of this
century, some 250 million people have been taking it annually to combat two of the world’s
most devastating, disfiguring, debilitating and stigma-inducing diseases, Onchocerciasis and
Lymphatic filariasis. Most of the recipients live in remote, rural, desperately under-resourced
communities in developing countries and have virtually no access to even the most rudimentary
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of medical interventions. Moreover, all the treatments have been made available free of charge
thanks to the unprecedented drug donation program.
The said 45-year-old drug has been described in detail in the report. This helps to compare
Ivermectin against the drugs available currently for the treatment of COVID. With WHO
predicting the global number to touch 10 million soon, we need a drug that has high efficacy
and low side effects. The number of researches across the globe, the history of drugs, lack of
side effects and its economic availability are evident and thus there is an urgent need to push
forward for a fast tracked clinical trial. It will be a matter of pride for India, if we become the
first country to conclude the accelerated clinical trials with a positive outcome nationwide (or
at least in the red zones where infection is increasing beyond manageable limit) of this 50 years
old drug with very good safety profile.

Table of Content
Preface 1
Table of Content 3
About COVID-19 4
A. COVID-19 Timeline 4
B. Why is Ivermectin a treatment candidate for COVID-19? 5
About Ivermectin 6
A. Onchocerciasis Disease 6
B. Discovery of Ivermectin 7
C. Pharmacokinetics and Pharmacodynamics of Ivermectin 8
D. Bioavailability (BA) and Bioequivalence (BE) Intelligence of Ivermectin 10
E. Adverse drug event [16] 11
Clinical Trials and Scientific Publications 13
A. Research 1: Pivoting point that brought spotlight on Ivermectin - Monash research 13
B. Research 2: ICON (Ivermectin in COVID Nineteen) Study [19] 15
C. Trials of Ivermectin across the world 16
Use of Ivermectin across the world 19
A. Peru research: 19
B. Bangladesh Doctors: 19
C. Use of Ivermectin by South American Nations against COVID: 20
WHO Bulletin: 21
A. WHO: Mass treatment with Ivermectin - an underutilized public health strategy [35] 21
B. WHO mass drug administration of Ivermectin 22
Ivermectin in India against COVID-19 23
A.Use in Mumbai Hospital 23
B. Trials in the country [40] 23
Indian production of Ivermectin [41] [42] [43] [44] 26
Comparison of Ivermectin and drugs available for COVID Treatment 34
Conclusion 35
Future research areas 36

About COVID-19
The coronavirus COVID-19 pandemic has caused a global health crisis of our time and the
greatest challenge we have faced since World War II. Since its emergence in China late last
year, the virus has spread to every continent except Antarctica. Cases are rising daily in all the
affected countries and forcing them to go into lockdown which has impacted the economies of
each country and it is taking all the countries back by 5 to 7 years. Hence COVID-19 is much
more than a health crisis. COVID-19 is a highly contagious SARs-CoV-2 coronavirus that is
rapidly spreading through both our most vulnerable and healthy population.
A. COVID-19 Timeline
With over a few lakh cases in the country and doubling rate at over 15 days, India requires
urgent control. This is possible only through use of proper drugs and vaccines. The available
drugs for corona have been divided into three sections, based on the stage at which they are in
use. To achieve the aim of flattening the curve, it is important to reduce the number of patients
from entering the moderate stage from the mild stage. Such drugs that are effective in mild
stages can help break the chain.
The virus spreads takes place due to the viral load of an infected person. Virus gets inside the
body of a healthy person and starts affecting the lungs. New virus starts growing at the site and
starts damaging cells by killing it. Immune system recognizes an intruder and signals the body

by releasing chemicals. At this point of time, the person needs to quarantine to arrest further
spread. If the condition of the patient deteriorates further he will need ICU care, ventilation and
in extreme cases even life support.
B. Why is Ivermectin a treatment candidate for COVID-19?

The latest research from a team at Monash University's Biomedicine Discovery Institute (BDI)
and the Peter Doherty Institute of Infection and Immunity indicated that Ivermectin could form
the basis of a Covid-19 vaccine given that it has proven successful in in vitro tests against other
viruses, although human studies will be required to test its efficacy against the coronavirus.
Ivermectin has many possible benefits including its antimicrobial, antiviral and anti-cancer
properties like the product of
curiosity. It is highly successful
against many, including certain
viruses, micro-organisms. In this
comprehensive systematic
review, antiviral effects of
Ivermectin are summarized
including in vitro and in vivo
studies over the past 50 years.
[1]
In a recent in vitro study, the
Vero/hSLAM cells infected with
the SARS-CoV-2 or COVID-19
virus were exposed to 5 µM
Ivermectin in 48 h, and a 5000-fold reduction in viral RNA was found The results showed that
treatment with Ivermectin effectively kills almost all viral particles within 48 hours. The study
has been the first one to assess Ivermectin’s antiviral effect on the body. [2]
Later the potential of the drug was acknowledged and a full-fledged study was proposed on the
drug. Also, the fact that Ivermectin has previously been effective against HIV, Dengue, Simian
Virus, Zika Virus, Influenza all of these being RNA Virus, the chances have been predicted for
Ivermectin to be a cure for covid-19s.

About Ivermectin
Ivermectin is a broad spectrum
antiparasitic agent that is also
referred to as ‘wonder drug’[3]. It
falls under the Ivermectin family of
medications which includes drugs and
pesticides that are used in the
treatment of parasitic worms and
insect pests. Ivermectin is a part of
the World Health Organization’s list
of essential medicines *4+ under the ‘Antifilarials’ category.
A. Onchocerciasis Disease
The origins of Ivermectin as a
human drug are inextricably
linked with Onchocerciasis, also
known as River Blindness. It is
caused by infection caused by
Onchocerca volvulus worms.
After mating, female worms
can release up to 1000
microfilariae a day for some
10–14 years. These move
through the body, and when
they die they cause a variety of
conditions, including skin
rashes, lesions, intense itching,
oedema and skin
depigmentation These
Microfilariae also invade the
eye, causing visual impairment and loss of vision. Onchocerciasis is the second leading cause
of blindness caused by an infectious disease. The disease causes visual damage for some 1–2
million people, around half of whom become blind.
In the early 1970s, the disease was endemic in 34 countries: 27 in Africa; 6 in the Americas; and
1 in the Arabian Peninsula. The World Health Organization (WHO) later estimated that 17.7
million people were infected worldwide, of whom some 270,000 were blind, and another
500,000 severely visually disabled. [5]

B. Discovery of Ivermectin
The Onchocerciasis Control Programme was set up in 1974. At exactly this time, a specialized
novel anthelmintic mouse screening model in Merck’s research laboratories was identifying the
avermectins in the microbial sample sent by the Kitasato Institute, of which Ivermectin would
become the most successful derivative.
Ivermectin, under the brand

name of “Mectizan” for
human use was registered in
1987. It was donated by the
manufacturing company,
Merck & Co. Inc.to treat
onchocerciasis in all
endemic countries for as
long as it was needed. It
swiftly became the drug of
choice for Onchocerciasis
treatment due to its unique
and potent microfilaricidal
effects, the absence of severe side effects and its excellent safety. [5]
Since the prodigious drug donation operation began, 1.5 billion treatments have been
approved. Latest figures show that an estimated 186.6 million people worldwide are still in
need of treatment, with over 112.7 million people being treated yearly, predominantly in
Africa.

C. Pharmacokinetics and Pharmacodynamics of Ivermectin

The broad-spectrum antiparasitic agent Ivermectin has been very recently found to inhibit
SARS-CoV-2 in vitro and proposed as a candidate for drug repurposing in COVID-19. We analyze
the vitro antiviral activity end-points from the pharmacokinetic perspective. The available
pharmacokinetic data from clinically relevant and excessive dosing studies indicate that the
SARS-CoV2 inhibitory concentrations are not likely to be attainable in humans.[6]
The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded
positive sense RNA virus that is closely related to severe acute respiratory syndrome
coronavirus (SARS-CoV). Studies on SARS-CoV proteins have revealed a potential role for
IMPα/β1 during infection in signal-dependent nucleocytoplasmic shuttling of the SARS-CoV
Nucleocapsid protein (Rowland et al., 2005; Timani et al., 2005; Wulan et al., 2015), that may
impact host cell division (Hiscox et al., 2001; Wurm et al., 2001). In addition, the SARS-CoV
accessory protein ORF6 has been shown to antagonize the antiviral activity of the STAT1
transcription factor by sequestering IMPα/β1 on the rough ER/Golgi membrane (Frieman et al.,
2007). Taken together, these reports suggested that Ivermectin's nuclear transport inhibitory
activity may be effective against SARS-CoV-2.
Ivermectin is a semisynthetic analogue of the natural product avermectin B1a, a lipophilic
macrolide isolated from Streptomyces avermitilis developed as a crop management insecticide.
Its mode of action on target species is by potentiating GABA-mediated neurotransmission and
by binding to glutamategated Cl- channels, found only in invertebrates. The drug induces tonic
paralysis of the musculature of susceptible parasites, and eventually death. At the
recommended doses, Ivermectin does not readily penetrate the CNS of mammals, where GABA
functions as a neurotransmitter, Conversely, in healthy volunteers and infected patients the
drug is usually well tolerated at the therapeutic dose ranges. A recent meta-analysis has shown
that even larger doses (up to 800 µg/kg) with a several years’ period of follow-up could be well
tolerated in patients with parasitic infections. The largest dose intensity with registered
pharmacokinetic parameters in healthy subjects is 120 mg, corresponding to up to 2000
µg/kg12. As evident from the analyzed pharmacokinetic data both the clinically applied dosage
schedules and the aforementioned excessive 120 mg dose yield blood levels at the
nanogram/ml i.e. nanomolar range. These concentrations are orders of magnitude lower, as
compared to the in vitro antiviral end-points, described in the study of Caly et al11. Table 2
summarizes the in vitro inhibitory concentrations, recalculated in ng/ml (based on a molecular
weight of 875.1) to allow direct juxtaposition with the pharmacokinetic parameters in Table 1.
Moreover, the in vitro data have been compared to the Cmax values, obtained after 36 mg and
120 mg doses corresponding to dose intensities of up to 700 µg/kg17 or 2000 µg/kg12
respectively, with calculation of the corresponding exposure ratios. The analyzed data show
that at least at the clinically relevant dose ranges of Ivermectin the published in vitro inhibitory
concentrations and especially the 5 µmol/L level causing almost total disappearance of viral
RNA are virtually not achievable with the heretofore known dosing regimens in humans. The 5
µmol/L concentration is over 50 times higher than the levels obtainable after 700 µg/kg17 and
17 times higher vs. the largest Cmax found in the literature survey (247.8 ng/ml) 12. Moreover,
the authors` claim for achieving viral inhibition with a single dose is inappropriate because
practically the infected cells have been continuously exposed at concentrations that are
virtually unattainable even with excessive dosing of the drug. With other words the

experimental design is based on clinically irrelevant drug levels with inhibitory concentrations
whose targeting in a clinical trial seems doubtful at best. [7]
The plasma systemic exposures increase proportionally with doses between 6 and 120 mg.
After single 12 mg doses of oral Ivermectin (tablet) in healthy volunteers, the mean peak
plasma concentrations were from 23.5 to 50 ng/mL. Ivermectin elimination curve might be
subject to enterohepatic recycling. Ivermectin is widely distributed in the body with a volume of
distribution about 3.1 and 3.5 L/kg, after ingesting 6 and 12 mg of Ivermectin, respectively. In
addition, Ivermectin is approximately 93% bound to plasma proteins, mainly to serum albumin.
[8]
Ivermectin is extensively metabolized in vitro by liver microsomal cytochrome P450 3A4 to

hydroxylated and demethylated metabolites[15]. Ivermectin and its metabolites appear to be
eliminated mainly in the faeces, with minimal urinary excretion (≤ 1% of the administered
dose). The mean half-life of Ivermectin when administered orally is ranging from about 15 to
20 h
The kinetics of Ivermectin disposition and metabolism in ruminant livestock and horses were
reviewed with particular emphasis on the influence of route of administration and it was found
out that injection of the subcutaneous formulation of Ivermectin prolongs plasma residence
time and persistence of drug residues particularly in liver and fat. Increasing the organic solvent
content of subcutaneous formulations slows the release of drug from the injection site and
thereby prolongs its presence in the bloodstream. [9]
A specific reversed-phase HPLC-assay with sensitive fluorometric detection has been developed
to measure the potent new antiparasitic agent Ivermectin (CAS 70288-86-7) in human plasma
(and urine). The lower limit of the method was 1 ng/ml and the intra-/interassay variability
averaged 4.5/6.9%, respectively. The assay was applied for measuring plasma (urine)
concentrations of Ivermectin upto 56 (72 h) following a single oral dose of 6 and 12 mg. No
unchanged or conjugated Ivermectin could be detected in urine. Plasma concentrations
increased linearly with dose but elimination half-life (12.6/13.4 h) was independent of the
administered dose. Thus, the method is applicable for monitoring plasma levels during clinical
and pharmacokinetic trials with Ivermectin to evaluate its most efficacious dosage regimen.
[10]
Although the efficacy of Ivermectin has been established in humans against several parasite
diseases, the pharmacokinetic properties of this compound are less well known in humans
compared to animals. Potential drug-drug interactions and drug-food interactions exist for
Ivermectin, which should be considered during therapeutic use of this drug. [11]
Ivermectin has shown effective pharmacological activity towards various infective agents,
including viruses. The paper by Emanuele Rizzo proposes an alternative mechanism of action
for this drug. This will make it capable of having an antiviral action, including that against the
novel coronavirus. [12]

D. Bioavailability (BA) and Bioequivalence (BE) Intelligence of

Ivermectin [13] [14]
Bioavailability is a measurement of the rate and extent to which a therapeutically active
chemical is absorbed from a drug product into the systemic circulation and becomes available
at the site of action. For most drugs that are taken orally, the active ingredients are released in
the gastrointestinal (GI) tract and arrive at their site of action via the systemic circulation. The
relative bioavailability estimate is useful in comparing the extent to which different drug
formulations of the same active ingredient are absorbed. If there is a relationship between
active moiety plasma concentration and clinical efficacy, knowledge of the bioavailability and
disposition kinetics of the active compound would be particularly useful in the development of
dosage forms and the comparison of routes of administration.
A guideline for Bioequivalence studies has been included below [15].
Dose: For Ivermectin marketed as 3 mg tablets, the use of a single tablet is recommended to
reduce the variability that can be caused by different gastric emptying times of the different
tablets, unless a higher therapeutic dose is necessary for bio-analytical reasons (i.e. insufficient
lower limit of quantitation to detect levels of 5% of Cmax). However, if additional strengths are
developed in the future in order to simplify the administration by reducing the pill burden, the
new higher strengths should be tested unless it is shown that Ivermectin is a highly soluble
drug.
Fasting/fed: The bioequivalence study should be conducted in the fasting state as Ivermectin
should be administered in fasting state.
Subjects: Healthy adult subjects should be used. It is not necessary to include patients in the
bioequivalence study.
Analytical considerations: The measurement of Ivermectin B1a in plasma is feasible (LLOQ =

0.2 ng/ml) and the use of the parent drug is considered to be more discriminative to differences
in the biopharmaceutical performance of the drug products. Therefore, bioequivalence should
be based on the determination of Ivermectin B1a.
Sample size: There is limited data on intra-subject variability of Ivermectin AUC0-72h and Cmax
in humans in the fasting state. These limited data suggest that variability is >30% (approx.
30−40%).
Washout: Taking into account the elimination half-life of Ivermectin in the fasting state of
about 53 hours, a washout period of approximately 4 weeks is considered sufficient to prevent
carry over. However, this value should be employed cautiously since the existence of
enterohepatic recycling may modify this value.
Blood sampling: Blood sampling should be more intensive between 2 and 6 hours after
administration to properly characterize the Cmax of Ivermectin. Considering the elimination
half-life, it is sufficient to take blood samples up to 72 hours after administration for the
characterization of Ivermectin pharmacokinetics.

Parent or metabolite data for assessment of bioequivalence: The parent drug is considered to
best reflect the biopharmaceutical quality of the product. Therefore, bioequivalence should be
based on the determination of Ivermectin B1a.
Statistical considerations: The data for Ivermectin should meet the following bioequivalence
standards in a single dose, crossover design study:
a. The 90% confidence interval of the relative mean AUC0-72h of the test to reference
product should be within 80–125%
b. The 90% confidence interval of the relative mean Cmax of the test to reference product
should be within 80−125%.
E. Adverse drug event [16]

Ivermectin is a fairly safe drug and acts as an anti-infective agent with activity against several
parasitic nematodes and scabies and is the treatment of choice for onchocerciasis (river
blindness). It is typically given as one or two oral doses. Ivermectin therapy has been associated
with minor, self-limiting serum aminotransferase elevations and very rare instances of clinically
apparent liver injury.
Irritant Environmental
Acute Toxicity Health Hazard
Hazard
Toxicity: LD50 = 29.5 mg/kg (Mouse, oral). LD50 = 10 mg/kg (Rat, oral).
Adverse effects include muscle or joint pain, dizziness, fever, headache, skin rash, fast
heartbeat.
Clinical studies have been carried out to examine the adverse effects of Ivermectin (for diseases
other than COVID-19), as seen in the following sections (i) and (ii).
(i) Strongyloidiasis
In four clinical studies involving a total of 109 patients given either one or two doses of 170 to
200 mcg/kg of STROMECTOL, the following adverse reactions were reported:
a. Body as a Whole: Fatigue (0.9%), abdominal pain (0.9%)
b. Gastrointestinal: Anorexia (0.9%), constipation (0.9%), diarrhea (1.8%), nausea (1.8%),

vomiting (0.9%)

c. Nervous System/Psychiatric: Dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor

(0.9%)
d. Skin: Pruritus (2.8%), rash (0.9%), and urticaria (0.9%).
(ii) Onchocerciasis
In clinical trials involving 963 adult patients treated with 100 to 200 mcg/kg STROMECTOL,
worsening of the following Mazzotti reactions during the first 4 days’ post-treatment were
reported:
a. Arthralgia/synovitis (9.3%)
b. Axillary lymph node enlargement and tenderness (11.0% and 4.4%, respectively)
c. Cervical lymph node enlargement and tenderness (5.3% and 1.2%, respectively)
d. Inguinal lymph node enlargement and tenderness (12.6% and 13.9%, respectively)
e. Other lymph node enlargement and tenderness (3.0% and 1.9%, respectively),
f. Pruritus (27.5%)
g. Skin involvement including edema, popular and pustular or frank urticarial rash (22.7%)
h. Fever (22.6%)
Post-Marketing Experience for All Indications
The following adverse reactions have been reported since the drug was registered overseas:
hypotension (mainly orthostatic hypotension), worsening of bronchial asthma, toxic epidermal
necrolysis, Stevens-Johnson syndrome, seizures, elevation of liver enzymes, and elevation of
bilirubin.
Achi community of south-east Nigeria was given mass Ivermectin therapy for onchocerciasis.
7556 subjects were dosed. 992 patients complained of adverse effects, mostly within one
week of dosing. In 962 subjects (97%), adverse events were mild and did not prevent work.
Common effects included: Oedema (47·4%), headache (46·4%), and worsening of rash (24·4%)

Clinical Trials and Scientific Publications
A. Exclusion criteria for research

1. Known history of Ivermectin allergy
2. Hypersensitivity to any component of Stromectol
3. COVID-19 Pneumonia
a. Diagnosed by the attending physician
b. Identified in a chest X-ray
4. Fever or cough present for more than 48 hours
5. Positive IgG against SARS-CoV-2 by rapid test
6. Age under 18 or over 60 years
7. The following co-morbidities (or any other disease that might interfere with the study in
the eyes of the investigator): Immunosuppression, Chronic Obstructive Pulmonary
Disease, Diabetes, Hypertension, Obesity, Acute or chronic renal failure, History of
coronary disease, History of cerebrovascular disease, Current neoplasm
8. Recent travel history to countries that are endemic for Loa loa (Angola, Cameroon,
Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial,
Guinea, Gabon, Republic of Congo, Nigeria and Sudan)
9. Current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem,
spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole,
cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate
drugs such as warfarin.
B. Research 1: Pivoting point that brought spotlight on Ivermectin -

Monash research
Background:
The research on Ivermectin for COVID-

19 came into consideration due to a
collaborative study by Monash
University’s Biomedicine Discovery
Institute (BDI) and the Peter Doherty
Institute of Infection and Immunity
(Doherty Institute), both in Australia.
The study was led by Dr. Kylie Wagstaff,
along with Professor David Jans, both
from BDI.
Dr. Wagstaff had made a previous
breakthrough finding on Ivermectin in
2012, when she identified the drug and
its antiviral activity along with Professor David Jans, who has been researching Ivermectin’s

antiviral properties for more than 10 years with different viruses. Dr. Wagstaff and Professor
Jans began their work on SARS-CoV-2 as soon as the pandemic was reported to have started
[17].
Research details [18]:
i. Methodology 1: The antiviral activity of Ivermectin towards SARS-CoV-2 was studied by
infecting Vero/hSLAM cells with SARS-CoV-2 isolate Australia/VIC01/2020 at an MOI of 0.1
for 2 h, followed by the addition of 5 μM Ivermectin. Supernatant and cell pellets were
harvested at days 0–3 and analysed by RT-PCR for the replication of SARS-CoV-2 RNA.
ii. Results 1: At 24 h, there was a 93% reduction in viral RNA present in the supernatant
(indicative of released virions) of samples treated with Ivermectin compared to the vehicle
DMSO. Similarly, a 99.8% reduction in cell-associated viral RNA (indicative of unreleased and
unpackaged virions) was observed with Ivermectin treatment. By 48 h this effect increased
to an ~5000-fold reduction of viral RNA in Ivermectin-treated compared to control samples,
indicating that Ivermectin treatment resulted in the effective loss of essentially all viral
material by 48 h. Consistent with this idea, no further reduction in viral RNA was observed
at 72 h. Further, no toxicity of Ivermectin was observed at any of the time points tested, in
either the sample wells or in parallel tested drug alone samples.
iii. Methodology 2: To further determine the effectiveness of ivemectin, cells infected with
SARS-CoV-2 were treated with serial dilutions of Ivermectin 2 h post infection and
supernatant and cell pellets collected for real-time RT-PCR at 48 h.
iv. Results 2: Similar to the aforementioned results, a >5000 reduction in viral RNA was
observed in both supernatant and cell pellets from samples treated with 5 μM Ivermectin
at 48 h, equating to a 99.98% reduction in viral RNA in these samples. Again, no toxicity was
observed with Ivermectin at any of the concentrations tested. The IC50 of Ivermectin
treatment was determined to be ~2 μM under these conditions.
Conclusion:
The in vitro studies demonstrated that Ivermectin can stop SARS-CoV-2 growth in cell cultures
by eradicating all genetic information within two days. An Ivermectin dose of 5 μM had an
inhibitory action on the novel coronavirus, reducing the load of viral RNA by 5,000 times in 48
hours. These findings were published in Antiviral Research. As a result, researchers all around
the world started studying the effect of Ivermectin on SARS-CoV-2. In vivo studies (clinical trials)
have also started around the world.
Key Findings:
● Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro.
● A single treatment gives ~5000-fold reduction in virus at 48 h in cell culture.
● Ivermectin is FDA-approved for parasitic infections, and therefore has a potential for
repurposing.
● Ivermectin is widely available, due to its inclusion on the WHO model list of essential
medicines.

Research 2: ICON (Ivermectin in COVID Nineteen) Study [19]

Background:
As of May 24th, 2020, the CDC recorded nearly 100,000 people having died of Covid-19 with at
least 1,639,099 confirmed infections having been reported in the US and its territories. Covid-
19 presents an unprecedented challenge to identify effective therapy for prevention and
treatment. Currently, there is no evidence from randomized controlled trials of any potential
therapy improving survival outcomes in patients with confirmed disease.
Ivermectin has previously been studied as a therapeutic option for viral infections with in vitro
data showing some activity against a broad range of viruses, including HIV, Dengue, Influenza
and Zika virus.2,3 In a recent study, Wagstaff et al, demonstrated that Ivermectin was a potent
in-vitro inhibitor of SARS-CoV-2, showing a 99.8% reduction in viral RNA after 48 hours.
However, in-vivo efficacy of Ivermectin in SARS-CoV-2 infection in humans has not previously
been reported.
Research details:
Methodology: Patients in the Ivermectin group received at least one oral dose of Ivermectin
at 200 micrograms/kilogram in addition to usual clinical care. The decision to prescribe
Ivermectin, hydroxychloroquine, azithromycin or other medications was at the discretion of
the treating physicians, however hospital guidelines were established for the use of these
agents as well as for cardiac and QT monitoring for patients receiving hydroxychloroquine.
Oxygen and ventilatory support were applied per the customary care.
Results: The primary outcome was all-cause in-hospital mortality. Patients were considered
a “survivor” if they left the hospital alive, or if their status in the hospital changed from
active care to awaiting transfer to a skilled facility. The latter outcome was necessitated by
the requirement that two consecutive negative nasopharyngeal swab specimens for SARS-
CoV-2, collected equal to or greater than 24 hours apart, were necessary for a patient to be
accepted to a skilled nursing facility. Secondary outcomes included subgroup mortality of
patients with severe pulmonary involvement, extubation rates for patients requiring
mechanical ventilation, and length of hospital stay.
Conclusion:
Overall mortality was significantly lower in the Ivermectin group than in the usual care group
(15.0% vs 25.2%, for Ivermectin and usual care respectively, p=.03). Mortality was also lower
for Ivermectin treated patients in the subgroup of patients with severe disease (38.8% vs.
80.7%, p=.001). Differences in extubation rates between groups were not significant and there
was also no difference in length of hospital stay.

Key Findings:
● Ivermectin administration was significantly associated with lower mortality among
patients with COVID-19, particularly in patients with more severe disease.
● The Cox regression showed Ivermectin was associated with a significantly lower hazard
ratio for mortality of 0.37 (CI 0.19 - 0.70, p=.003).
C. Trials of Ivermectin across the world

Several studies have been planned by universities, institutes and hospitals across the globe. The
USA themselves have planned 18 randomized controlled studies and trials for Ivermectin on
covid. Few other trials for Ivermectin include:
University of Tanta, and Mansoura University, Egypt: The study’s

participants will receive a combination of Nitazoxanide, Ribavirin
and Ivermectin for a duration of seven days. Launched on April 15
2020, the first Tanta University Phase II/III randomized, parallel
·
assigned, five arm study, involves up to 100 patients with COVID-19.
In both studies, the Principal Investigator, Sherief Abd-Elsalam,
associate professor Faculty of Medicine, looks to a primary
endpoint involving the total number of patients with virological
cure over a duration of six-month period. [20]
University of Baghdad, Iraq: This influential Middle East institution

of higher learning is comparing in this Phase I study, the efficacy
and safety of 0use of Ivermectin in COVID-19 patients with
pneumonia. Ivermectin 0.2 mg/kg (12 mg adult dose) single dose is
repeated after 1 week combined with hydroxychloroquine 400 mg
daily compared to Hydroxychloroquine, plus placebo single one
dose repeated after 1 week. Put another way, they want to see if
adding Ivermectin to Hydroxychloroquine makes a difference to
those infected with COVID-19. The study started April 18, 2020 and
runs through until August 2020. 50 participants have been enrolled
for the research. [21]

General Directorate of Medical City, Iraq: The Phase I trial that

began on April 13, 2020 and completed on 5 June 2020. It was
aimed at finding the Efficacy of Ivermectin as Add on Therapy in
COVID19 Patients. Primary endpoint was Number of cured patients
in 4 weeks while secondary endpoint was Mean time to cure the
COVID-19 patients. [22]
University of Kentucky (UK), USA: The trial will investigate the

effectiveness of azithromycin, Ivermectin and camostat mesylate—
drugs that could inhibit replication of SARS-CoV-2, the virus that
causes the disease. The three will be tested either as stand-alone
therapies or in combination with the antimalarial drug
hydroxychloroquine. The trial has a “pick-the-winner” design,
which will allow UK researchers to rapidly understand what
potential therapies appear to be effective, guiding patients to
treatments that work and researchers to promising drugs that
warrant further investigation. [23]
Johns Hopkins University, USA: Planned to commence June 2020

for a year, the Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins will probe into whether bicalutamide or
Ivermectin can have an impact on hospitalized patients infected
with SARS-CoV-2. [24]
Clinica Universisad de Navarra, Spain: The study has been titled as

Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial (SAINT).
SAINT is a double-blind, randomized controlled trial with two
parallel groups that evaluates the efficacy of Ivermectin in
reducing nasal viral carriage at seven days after treatment in SARS-
CoV-2 infected patients who are at low risk of progression to severe
disease. The trial is currently planned at a single center in Navarra.
Primary endpoint is to determine the proportion of patients with a
positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7
post-treatment. [25]

Combined Military Hospital Lahore, Pakistan: This randomized,

controlled trial has been designed to investigate the efficacy of
Ivermectin in COVID-19 patients. Patients will be assigned to two
groups, including 1) that will be given Ivermectin with standard
chloroquine regimen, and 2) the other group will be given chloroquine
only. The outcomes will be recorded by documenting PCR reports at
48, 96 and 144 hours. The study was launched April 15, 2020 and runs
till July 2020. Recruiting 100 patients, the study precludes those with
severe conditions or comorbidities such as malignant disease,
diabetes, etc. [26]
Laboratorio Elea Phoenix S.A., Argentina: Argentina’s Laboratorio Elea

Phoenix S.A. (Elea Laboratories) has initiated a proof-of-concept clinical
trial with 45 patients to investigate the efficacy of Ivermectin as a
treatment for patients infected with SARS-CoV-2. The South American
pharmaceutical company based its decision on the important Monash
University lab study plus the fact that Ivermectin has been widely in use
for decades. [27]
Jose Manuel Arreola Guerra (Researcher): The study seeks to

investigate the safety and efficacy of a treatment involving
hydroxychloroquine and Ivermectin for serious COVID-19
infections in non-critical hospitalized patients. Prior to any
patient randomization the investigational team will assess
cardiovascular complications determined by the corrected QT
interval, related to hydroxychloroquine intake. For example, if a
patient is at high risk, they will be placed in an Ivermectin group
only or to placebo in an independent randomization [28]

Use of Ivermectin across the world

Apart from the number of study, research and clinical trials going around, some
nations have permitted use of Ivermectin. We have discussed a few of them in
brief.
A. Peru
Peru has accepted Ivermectin

as a COVID-19 treatment,
however the government’s
decision was not based on
formal, randomized controlled
trials. Instead, a network of
many doctors in and around
Peru drove a kind of
community movement to use
the medicine to treat COVID-
19. Doctors started using Ivermectin and reporting positive results to colleagues. The
government came to the conclusion that a sufficient number of experts in the country had
formed a consensus that could not be ignored [29]. Thus, Ivermectin is being used on a wide
scale in Peru, in combination with other drugs like hydroxychloroquine, azithromycin and
chloroquine phosphate. Dosage forms for the treatment of mild, moderate and severe forms of
COVID-19, using the above combinations, have been established [30].
B. Bangladesh:
Following the Monash-Doherty research, physicians at a Dhaka hospital have observed

cumulative efficacy of a combination therapy of Ivermectin and doxycycline in Covid-19
patients. The medication was tested in 60 patients who were staff members of Bangladesh
Medical College and Hospital. After 72 hours of drug administration, the majority of the
patients’ conditions started improving. The average recovery time was noted to be 11 days. Out
of 60 COVID-19 patients, all recovered as the combination of the two drugs were applied. This
paved way for clinical trials. The doctors have stated that Ivermectin should not be
administered to pregnant or breastfeeding women, children under five or weighing below 15
kg, and patients with liver diseases. After successful clinical trials, they have concluded that
Ivermectin gives promising results in mild cases, however, it remains ineffective in patients with
severe conditions [31].

C. South Americas:
South American Nations like Peru,

Bolivia, have been using Ivermectin
to fight against COVID-19. It has
been reported that many provinces
have already approved Ivermectin
as a treatment for SARS-CoV-2, the
virus behind COVID-19. While
Argentina is carrying out clinical
trials, many other countries have
started using the drug without
concrete scientific proof of its
effects in a vast population. For
example, Trinidad, a city in Bolivia,
initiated a campaign to combat
COVID-19 by distributing free doses of the anti-parasite drug in an effort to take on the
pathogen in the eastern region of the country where more have contracted the virus [32]. Thus,
there is a growing interest and even authorization of Ivermectin in some of the more
economically challenged South American nations [33].
On the left is image of Manuel

Negrete, former Mexican
footballer as he holds the anti-
parasite drug Ivermectin after
buying it with a medical
prescription at a local pharmacy
in Santa Cruz, Bolivia May 19,
2020. REUTERS/Rodrigo
Urzagasti

WHO Bulletin:
The World Health Organization bulletin on
Ivermectin covers its veterinary drug history
followed by its potential for human use. It has
valuable public health applications for
controlling strongyloidiasis, scabies and
filariasis. Ivermectin also acts against other
intestinal nematodes, but it is not the most
effective drug available. In control programmes
for filariasis, Ivermectin is the drug of choice in
areas with onchocerciasis, but can be replaced
by diethylcarbamazine for control of other
filarial diseases.
It is time to capitalize on the full public health

potential of Ivermectin. Carefully designed
studies to evaluate the efficacy of community-wide Ivermectin based control programmes for
strongyloidiasis and scabies in developing countries are indicated, as are similar studies in
marginalized communities in developed countries with high prevalence of these two diseases,
including indigenous communities in Australia [34].
A. WHO: Mass treatment with Ivermectin - an underutilized public health

strategy [35]
WHO, in their bulletin posted an issue stating the need to realize the full public health potential
of Ivermectin. Ivermectin has historically proved to be of valuable public health applications
such as controlling strongyloidiasis and scabies. It has helped in breaking the infection cycle
through its therapeutic effect and filariasis, through its effect on transmission.
A study has been mentioned that investigates changes in parasitological parameters and the
occurrence of side-effects after treatment with Ivermectin. The treatment was for a Brazilian
community, heavily parasitized with intestinal helminths and ectoparasites. Community
members, ineligible for Ivermectin, were treated with mebendazole, albendazole or
deltamethrin to achieve a high level of coverage. The findings of Ivermectin were highly
effective against Strongyloides stercoralis, with a 94% reduction in prevalence that was
sustained for nine months. This provided field evidence for a paper that predicted that
strongyloidiasis in heavily endemic communities could be successfully controlled with a highly
effective drug, owing to its low transmission potential. If similar success is achieved with COVID,
it can be a huge relief globally. This and the aim of realizing the potential of Ivermectin is
possible only through detailed and fast tracked trial of the drug.

B. WHO mass drug administration of Ivermectin
As discussed above, Onchocerciasis (also known as river blindness) can lead to blindness and
severe, debilitating skin irritation. Mass drug administration of Ivermectin 1 or 2 times annually
(for 10-20 years) to control or eliminate onchocerciasis. High-quality evaluations have
demonstrated that Ivermectin is effective in suppressing the worms that cause onchocerciasis.
[36]
Ivermectin is widely used in mass drug administrations for controlling neglected parasitic
diseases, and can be lethal to malaria vectors that bite treated humans. The hypothesis of
frequently repeated mass administrations of Ivermectin to village residents was tested. It
reduces clinical malaria episodes in children and would be well tolerated with minimal harms. It
could be a powerful and synergistic new tool to reduce malaria transmission in regions with
epidemic or seasonal malaria transmission, and the prevalence and intensity of neglected
tropical diseases. [37]
Scabies was added to the World Health Organization list of neglected tropical diseases. Scabies
is a skin disease caused by a mite that burrows under the skin and is transmitted through
prolonged skin-to-skin contact. Mass drug administration (MDA) campaign was adopted to
treat scabies with oral Ivermectin. In small community-based trials, mass drug administration of
Ivermectin has been shown to substantially decrease the prevalence of both scabies and
secondary impetigo. In 2018, Ivermectin was proposed for inclusion on the WHO Model List of
Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc) for the
indication of Scabies.[38]

Ivermectin in India against COVID-19

The use and study of Ivermectin is not just limited to outside India. Even in India,
several doctors are of the view that Ivermectin can be a top candidate for curing
COVID. One example of such covered use of Ivermectin is from the city that has
the leading number of corona cases.
A. Use in Mumbai Hospital

In hospitals of Mumbai, Ivermectin is being given to the patients in combination with
doxycycline. It is administered to those having heart rhythm problems and who cannot be
given the usual combination of antimalarial drug HCQS and antibiotic. The state task force
advised its use. The Maharashtra task force members spoke to the doctors from Bangladesh
and felt it could be used in India as well. Dr. Gautam Bhansali from Bombay Hospital said 20-30
patients in the hospital have been given the combination. Infectious diseases specialist Dr. Om
Srivastava said the combination has to be studied before it can be widely advised.[39]
B. Trials in the country [40]

Clinical trials registry- India (CTRI) at ICMR- National Institute of Medical Statistics is an online
public record system for registration of clinical trials being conducted in India. The mission of
CTRI is to encourage all clinical trials conducted in India to be prospectively registered, i.e.
before the enrolment of the first participant.
Clinical trials related to Ivermectin and COVID-19. All of the trials for Ivermectin as a treatment
of COVID-19 in India are either in the recruitment phase or not recruiting phase. There is a
need to fast track the trials for a drug with such high candidature.

Sr. Type of Recruitment Health Intervention

CTRI No. Public Title Location
No Trial Status Condition Name
1 CTRI/2020 “To study the Interven Total: Not Other Ivermectin Max Super
/04/02485 effectiveness tional Applicable specified Specialty
8 of Ivermectin Indian: Not viral hospital,
with standard Yet Recruiting diseases Saket (A
of care unit of
treatment Devki Devi
versus Foundation
standard of ),DELHI
care
treatment for
COVID 19
cases. A Pilot
Study
2 CTRI/2020 A clinical Trial Interven Total: Not Coronaviru Hydroxychloro Departmen

/04/02494 to Study the tional Applicable s as the quine t of
8 Effects of Indian: Not cause of Ciclesonide Medicine,D
Hydroxychlor Yet Recruiting diseases Ivermectin ELHI
oquine, classified
Ciclesonide elsewhere
and Other
Ivermectin in specified
treatment of viral
moderate diseases
COVID-19
illness

Sr. Type of Recruitment Health Intervention

CTRI No. Public Title Location
No Trial Status Condition Name
3 CTRI/2020 Can a Interven Total: Not Other Ivermectin Christian

/05/02506 medicine help tional Applicable specified Medical
8 in curing viral Indian: Not viral College
infection Yet Recruiting diseases Vellore,TA
MIL NADU
4 CTRI/2020 Study to Interven Total: Not Coronaviru Ivermectin R D Gardi

/05/02522 efficacy of tional Applicable s as the Medical
4 Ivermectin in Indian: Not cause of College,
patients of Yet Recruiting diseases Ujjain
COVID-19 classified ,MADHYA
elsewhere PRADESH
5 CTRI/2020 Study to Interven Total: Not Healthy Ivermectin R D Gardi

/05/02533 assess tional Applicable health care Medical
3 efficacy of Indian: Not workers or College,
Ivermectin as Yet Recruiting Healthy Ujjain
prophylaxis of contact of ,MADHYA
COVID -19 COVID 19 PRADESH
6 CTRI/2020 To study Interven Total: Not Coronaviru Tablet Symbiosis

/06/02596 effect of tional Applicable s as the Ivermectin University
0 Ivermectin Indian: Not cause of Hospital
drug in Yet Recruiting diseases and
patients classified Research
infected with elsewhere Centre,MA
SARS-CoV-2 HARASHTR
virus. A

Indian production of Ivermectin [41] [42] [43] [44]

Indian pharmaceutical industry has the largest number of US Food and Drug Administration
(USFDA) approved manufacturing facilities outside the US, and over 1,300 manufacturing
plants compliant with the World Health Organization (WHO) Good Manufacturing Practices.
Following is the record of brand names under which Ivermectin is sold in India
Brand Name Composition Company Quantity MRP Rs.
AGIMECT tab Ivermectin 12mg AEGIS 4 175

PHARMACEUTICALS
ASCAPIL tab Ivermectin 6mg NICHOLAS PRIMAL INDIA 1 16.27
ASCAPIL tab Ivermectin 6mg AHPL 4 65.09
AVERM PLUS Ivermectin 12mg BIOTAVIA LABS 105
BANDY PLUS Ivermectin 6mg, MANKIND PHARMA 1 23.90

tab albendazole 400mg
BANDY PLUS Ivermectin 12mg, MANKIND PHARMA 1 28.80

BENDEX PLUS Ivermectin 6mg, CIPLA 1 26.40

BIOVER tab Ivermectin 6mg BIOGENETIC 10 150

PHARMACEUTICALS
ECTIN tab Ivermectin 6mg ELFIN PHARMA 40 380
ECTOVER tab Ivermectin 12mg WORTH MRDICINES 10 199

ELECT DT tab Ivermectin 6mg CAPTAB BIOTEC 60 960
ELECT DT tab Ivermectin 12mg CAPTAB BIOTEC 60 1500
EVERGRIN-A Ivermectin 6mg, GENETIC PHARMA 1 18.72

EVERGRIN-A Ivermectin 1.5mg, GENETIC PHARMA 1 28.00

susp albendazole
200mg/5ml
EVERSON tab Ivermectin 6mg PARKINSON PHARMA 10 N.A.
EVERSON-A tab Ivermectin 6mg, PARKINSON PHARMA 10 N.A.

albendazole 400mg
EVERTIN-6 tab Ivermectin 6mg ZEE LABORATORIES 4 59
EVRINA tab Ivermectin 3mg PRIDE HEALTHCARE 500
EVRINA tab Ivermectin 6mg PRIDE HEALTHCARE 750
HESTIN tab Ivermectin 3mg ARTICON LABS 37.79
HESTIN tab Ivermectin 6mg ARTICON LABS 63
I-STAR tab Ivermectin 6mg ORGANIC LABS 48
IMEC-H tab Ivermectin 12mg GARY PHARMACEUTICALS 25
IMEC-M tab Ivermectin 6mg GARY PHARMACEUTICALS 13

IMECTIN tab Ivermectin 3mg PULSE 2 15

PHARMACEUTICALS

PHARMACEUTICALS

PHARMACEUTICALS
INOVER tab Ivermectin 3mg H. L. HEALTHCARE 8
INOVER tab Ivermectin 6mg H. L. HEALTHCARE 12
ISCO tab Ivermectin 3mg BENNET 32

PHARMACEUTICALS
IVAZED tab Ivermectin 6mg ZEDCHEM PHARMA 16
IVECOP-DT tab Ivermectin 3mg SHALAKS 2 11.60

PHARMACEUTICALS
IVECOP tab Ivermectin 6mg SHALAKS 1 10.50

PHARMACEUTICALS
IVECOP tab Ivermectin 12mg SHALAKS 1 15.60

PHARMACEUTICALS
IVEL tab Ivermectin 6mg DERMAVIN 9

PHARMACEUTICALS
IVEL 12 tab Ivermectin 12mg DERMAVIN 16

PHARMACEUTICALS

IVER-A tab Ivermectin 6mg, SHRI PHARMA 1 N.A.

albendazole 400mg
IVERCID tab Ivermectin 3mg EAST WEST PHARMA 2 19.8
IVERCID tab Ivermectin 6mg EAST WEST PHARMA 2 30
IVERCID tab Ivermectin 12mg EAST WEST PHARMA 2 48
IVERDIS tab Ivermectin 6mg MEDIS LAB (PRAGATI 4 64

BIOCARE)
IVERDIS tab Ivermectin 12mg MEDIS LAB (PRAGATI 4 95

BIOCARE)
IVERFAST-12 Ivermectin 12mg SUBODH IMPEX 280

tab
IVERFAST tab Ivermectin 12mg HERAMB HEALTHCARE 18
IVERIN tab Ivermectin 3mg SATVEN AND MER 2 13
IVERIN D S tab Ivermectin 6mg SATVEN AND MER 2 19
IVERIN tab Ivermectin 12mg SATVEN AND MER 10 220
IVERIV tab Ivermectin 12mg EAST AFRICAN (INDIA) 100 1860

REMEDIES
IVERMECTOL Ivermectin 3mg OCHOA 1 23.50

tab

IVERMECTOL Ivermectin 6mg OCHOA 2 42

tab
IVERMECTOL Ivermectin 12mg OCHOA 2 77.50

tab
IVERMECTOL Ivermectin 3mg SUN PHARMACEUTICAL 23.50

tab
IVERMECTOL Ivermectin 6mg SUN PHARMACEUTICAL 42

tab
IVERMECTOL Ivermectin 12mg SUN PHARMACEUTICAL 85

tab
IVERPIL tab Ivermectin 6mg PSYCHOTROPICS INDIA 22
IVERPIL tab Ivermectin 12mg PSYCHOTROPICS INDIA 15.98
IVERSCAB tab Ivermectin 6mg NuLIFE 39

PHARMACEUTICALS
IVERSCAB tab Ivermectin 12mg NuLIFE 53

PHARMACEUTICALS
IVERT tab Ivermectin 6mg TRIPADA BIOTEC 60
IVERT tab Ivermectin 12mg TRIPADA BIOTEC 90
IVER SOL 3 tab Ivermectin 3mg PSYCO REMEDIES 20 140

IV PAC tab Ivermectin 6mg PACIFIC INDIA 40
MECTIN tab Ivermectin 3mg MERIDIAN 1 8
MECTIN tab Ivermectin 6mg MERIDIAN 1 12. 80
MECTIN tab Ivermectin 12mg MERIDIAN 1 15.00
MERIBEN tab Ivermectin 6mg, MERIDIAN 1 22.50

albendazole 400mg
MERIBEN susp Ivermectin 3mg, MERIDIAN 10mL 30.80

albendazole
200mg/5ml
SCABERASE IF Ivermectin 12mg ROWAN BIOCEUTICALS 19.8

tab
SCABERASE IM Ivermectin 6mg ROWAN BIOCEUTICALS 47.97
SCAVISTA tab Ivermectin 3mg ZUVENTUS 1 11.80
SIVERMIN tab SAIMARK BIOTECH
SIVERMIN tab SAIMARK BIOTECH

SKINTIN tab Ivermectin 6mg AMRAY 1 18
SKINTIN tab Ivermectin 12mg AMRAY 1 25
TERGUM tab Ivermectin 6mg BIOSCIENCES 1 17

PHARMAKON
TROMER tab Ivermectin 6mg ELFIN PHARMA 40 380
VARZO tab Ivermectin 6mg ZODAK 1 12.60
VERMACT tab Ivermectin 3mg MANKIND PHARMA 11.26
VERMECTIN tab Ivermectin 6mg MICRO VISION 1 15.00
VERMECTIN tab Ivermectin 12mg MICRO VISION 1 22.52
VERMIN tab Ivermectin 6mg HALEDEW 1 16
VERMIN tab Ivermectin 12mg HALEDEW 1 20
VERMISCAB tab Ivermectin 6mg SIGMAN 1 16
VERMISCAB tab Ivermectin 12mg SIGMAN 1 20
VERMIZOLE tab Ivermectin 6mg, FITWEL 1 20

albendazole 400mg PHARMACEUTICALS
VERSIL-6 Ivermectin 6mg SANIFY (SILVER BIOTECH) 1 15
WARMY PLUS Ivermectin 1.5mg, ESQUIRE DRUG HOUSE 10mL 38.00

susp albendazole 200mg
XULTIVER-6 tab Ivermectin 6mg SYNTONIC LIFE SCIENCES 1 N.A.
XULTIVER-A tab Ivermectin 6mg, SYNTONIC LIFE SCIENCES 1 N.A.

albendazole 400mg

Comparison of Ivermectin and drugs available for

COVID Treatment
Parameters Dexa- Remdesivir Favipiravir Hydroxy- Ivermectin

methasone chloroquine
Cost Rs. 100 to Rs. 5000 per Rs.103 per Rs. 60 to Rs. 9 to
Rs.200 for a vial tablet Rs.100 per Rs.100 per
day’s dose strip strip
Side Effect Swelling, Adverse Liver Potential for Headache

rapid weight and Kidney teratogenicity Headache, dizziness,
gain, risk, nausea, and embryo dizziness, muscle pain,
headache, diarrhea, toxicity in nausea
dizziness, humans diarrhea,
nausea, stomach
bloating,
muscle cramps,
weakness vomiting
Primary Improved 28- Discharged Viral In-hospital Mean day of

Endpoint day mortality alive from Clearance mortality hospital stay
hospital time
Secondary Reduced need Reduction in Chest imaging Occurrence of Mean time to

Endpoint for intubation viral load improvement clinically viral PCR
and reduced rate significant negativization
hospital ventricular
length of stay arrhythmias
Patent Generic Patented Patented Generic Generic
Stage of use Moderate to Moderate to Initial to Moderate to Initial to

severe severe moderate severe moderate

Conclusion
The antiviral effects of Ivermectin on a broad range of RNA and DNA viruses have been studied
since 1970. Clinical trials around the world have shown the possibility that Ivermectin could
be a useful antiviral agent in several viruses including those with positive-sense single-
stranded RNA, in similar fashion. Since significant effectiveness of Ivermectin is seen in the
early stages of infection in experimental studies, it is proposed that Ivermectin administration
may be effective in the early stages or prevention.
Ivermectin, owing to its antiviral activity, may play a pivotal role in several essential biological
processes; therefore it could serve as a potential candidate in the treatment of different
types of viruses including COVID-19.

Future research area
The recent findings regarding Ivermectin warrant rapidly implemented controlled clinical trials
to assess its efficacy against SARS-CoV-2. These trials may open a new field of research on the
potential use of Ivermectin antiparasitic drugs, including compounds with an improved
pharmacokinetic profile, as antivirals.
However, because of the following points, extreme due diligence and regulatory review are
needed before testing Ivermectin in severe disease.
(1) Ivermectin, which targets glutamate-gated chloride channels in invertebrates, may cross-
target the GABA-gated chloride channels present in the mammalian central nervous system
(CNS) and cause neurotoxicity.19 This is normally prevented by an intact blood–brain barrier
(BBB), but in patients with a hyperinflammatory state, endothelial permeability at the BBB may
be increased and cause leaking of drugs into the CNS, potentially causing harm.20,21
(2) Boosted antiretrovirals such as lopinavir/ritonavir and darunavir/cobicistat, which have

been widely used against SARS-CoV-2 based on limited evidence, and a number of other drugs,
are potent inhibitors of cytochrome P450 3A4, the main metabolic pathway for Ivermectin.
Concurrent use of these drugs will result in increased systemic exposure to Ivermectin.
Furthermore, ritonavir and cobicistat can readily inhibit one of the main efflux pumps in the
BBB, P-glycoprotein, further favoring neurotoxicity.22,23 However, it is encouraging that a
recent analysis of Ivermectin-related neurotoxic adverse events reported to the WHO Program
for International Drug Monitoring found only one case of 1,668 reports in which concomitant
use of antivirals was associated with neurotoxicity.[45]
A path to consider is evaluation first of impacts on virologic outcomes in uncomplicated, low-

risk patients early in the course of the disease. This is imperative to stop the spread of viruses
further and reduce the number of active cases. If Ivermectin is able to do that, it will be of
huge help to the already crumbling health infrastructure globally. With positive results in trial,
few countries approving it as a drug for COVID and the ability of India to produce Ivermectin on
a large scale, it becomes very important for India to speed up their clinical trials on Ivermectin.

References
[1] https://www.nature.com/articles/s41429-020-0336-z.pdf
[2] https://www.sciencedirect.com/science/article/pii/S0166354220302011
[3] A. Crump and S. Omura, “Ivermectin, ‘Wonder drug’ from Japan: The human use
perspective,” Proc. Japan Acad. Ser. B Phys. Biol. Sci., vol. 87, no. 2, pp. 13–28, 2011.
[4] The International Pharmacopoeia, “19th WHO Model List of Essential Medicines,”
Http://Www.Who.Int/Medicines/Publications/Essentialmedicines/En, no. April, pp. 1–43, 2015.
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043740/
[6] https://www.tandfonline.com/doi/full/10.1080/13102818.2020.1775118
[7] https://www.medrxiv.org/content/10.1101/2020.04.11.20061804v1.full.pdf
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[12]https://link.springer.com/article/10.1007/s00210-020-01902-5
*13+ “Notes on the design of bioequivalence study: Ivermectin,” 2019.
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with_COVID19
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2020

This is a FREE report generated based on Crowd-searched intelligence on

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For more information on this report:

A PatBnB & Gridlogics initiative 1

A PatBnB initiative | ©Bots ‘N Brains, 2020

A PatBnB initiative | ©Bots ‘N Brains, 2020

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B. Why is Ivermectin a treatment candidate for COVID-19?

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Ivermectin, under the brand

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C. Pharmacokinetics and Pharmacodynamics of Ivermectin

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Ivermectin is extensively metabolized in vitro by liver microsomal cytochrome P450 3A4 to

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D. Bioavailability (BA) and Bioequivalence (BE) Intelligence of

A guideline for Bioequivalence studies has been included below [15].

Analytical considerations: The measurement of Ivermectin B1a in plasma is feasible (LLOQ =

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E. Adverse drug event [16]

a. Body as a Whole: Fatigue (0.9%), abdominal pain (0.9%)

b. Gastrointestinal: Anorexia (0.9%), constipation (0.9%), diarrhea (1.8%), nausea (1.8%),

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c. Nervous System/Psychiatric: Dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor

d. Skin: Pruritus (2.8%), rash (0.9%), and urticaria (0.9%).

Post-Marketing Experience for All Indications

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Clinical Trials and Scientific Publications

A. Exclusion criteria for research

B. Research 1: Pivoting point that brought spotlight on Ivermectin -

The research on Ivermectin for COVID-

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Research 2: ICON (Ivermectin in COVID Nineteen) Study [19]

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C. Trials of Ivermectin across the world

University of Tanta, and Mansoura University, Egypt: The study’s

University of Baghdad, Iraq: This influential Middle East institution

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General Directorate of Medical City, Iraq: The Phase I trial that

University of Kentucky (UK), USA: The trial will investigate the

Johns Hopkins University, USA: Planned to commence June 2020

Clinica Universisad de Navarra, Spain: The study has been titled as

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Combined Military Hospital Lahore, Pakistan: This randomized,

Laboratorio Elea Phoenix S.A., Argentina: Argentina’s Laboratorio Elea

Jose Manuel Arreola Guerra (Researcher): The study seeks to

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Use of Ivermectin across the world

Peru has accepted Ivermectin

Following the Monash-Doherty research, physicians at a Dhaka hospital have observed

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South American Nations like Peru,

On the left is image of Manuel

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