Ivermectin. What is it?

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Ivermectin. What is it?

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Why Ivermectin?

Dr. William Campbell
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“We wanted a sensationally novel anthelminthic,” he said, after his speech. “You can make novel chemicals, but because they are made by humans they are restricted by the limits of human knowledge.”(- Dr. William Campbell) Instead, he acquired thousands of microbial cultures from laboratories around the world.
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While looking for alternative solutions to parasites and infectious diseases in the late 1970s, William Campbell and his team at the pharmaceutical company Merck, looked to soil microorganisms. They were receiving samples of unwanted but unique soil microorganisms from a lab in Japan already isolating soil microorganisms.

In 1970, microbiologist Satoshi Ōmura collected a soil sample from woods close to a golf course in Kawana, on the south east coast of Honshu, Japan [6]. Ōmura isolated and cultured a Gram-positive bacterium, sample NRRL 8165–a then unknown species of Streptomyces, which was sent to William Campbell at Merck (along with 50 other strains of Streptomyces which were considered unusual in appearance or culture characteristics) to test for antiparasitic effects. NRRL 8165 cultures showed potent activity against Nematospiroides dubius (now known as Heligomosoides polygyrus) infection in mice, and the active components were purified, revealing a family of macrocyclic lactones. These naturally occurring compounds were named the avermectins (and the bacterium, Streptomyces avermitilis) to reflect the worm-free ‘averminous’ conditions they produced
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Ivermectin's History, Uses and the Mysterious Satoshi Soil Sample

Satoshi Omura cultured bacteria, which produce substances that inhibit the growth of other microorganisms. In 1978 he succeeded in culturing a strain from which William Campbell purified a substance, avermectin, which in a chemically modified form, ivermectin, proved effective against river blindness and elephantiasis.
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Despite decades of searching around the world, the Japanese microorganism remains the only source of avermectin ever found.1) Originating from a single Japanese soil sample and the outcome of the innovative, international collaborative research partnership to find new antiparasitics, the extremely safe and more effective avermectin derivative, ivermectin...
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Timeline of Ivermectin uses

1981

First introduced as a commercial parasite product for Animal Health

It is effective against a wide range of parasites, including gastrointestinal roundworms, lungworms, mites, lice and hornflies.7–12) Ivermectin is also highly effective against ticks
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1987

First approved for human use to treat Onchocerciasis. Onchocerciasis is also known as River Blindness. This parasitic worm lays eggs in humans by a fly bite. Once the eggs hatch the parasite finds the eye often and lays eggs inside!

After Ivermectin was approved for human use in 1987, Merck made an unprecedented move.

Following the registration of ivermectin (produced under the brand name Mectizan®) for human use in 1987, in a hitherto unprecedented move and with unheralded commitment, Mectizan® was donated by the manufacturing company, Merck & Co. Inc., to treat onchocerciasis in all endemic countries for as long as it was needed. The resultant drug donation programme was the first, largest, longest running and most successful of all and proved a model for all others that have followed.
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1997

Merck's Patent expires for Ivermectin

1998

Finally approved for treatment of lymphatic filariasis after many years of unnecessary delay.

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Ivermectin Drug Resistance

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Anthelmintic Resistance
IVM (Ivermectin) has been widely used in veterinary species for the prophylaxis and treatment of parasitic disease, often using a mass drug administration (MDA) strategy to protect all animals considered ‘at risk’. However, applying this blanket approach has resulted in rapid selection for parasitic nematodes that are capable of surviving drug treatment. Anthelmintic resistance is now a major global problem in the control of gastrointestinal roundworms of sheep, cattle, and horses [47], and there are now reports of IVM resistance in the canine heartworm
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Lots of various types of DNA/RNA studies and sequencing are being done to determine why some parasites, and nematodes in particular, develop drug resistance when others do not.

While the potential impact of population structure and genetic diversity (with the potential bottleneck of vector transmission for the filarial nematodes) remain unclear, increased effort to develop sensitive markers of resistance is warranted.
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New Uses for Ivermectin and Cancer

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IVM has a broad range of effects in many different organisms. Some of these effects may provide further clues to its mode of action in parasites and may have potential relevance in the treatment of human disease.
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high-dose IVM (up to 1.6 mg/kg) has previously been used successfully for symptomatic treatment of severe muscle spasticity in patients with spinal cord injuries [62]. More recently, IVM was shown to induce intracellular chloride flux in human leukaemia cells in vitro [63]. This was associated with an increase in the production of intracellular reactive oxygen species (ROS), leading to cell death in leukaemia cells, but not in normal haematopoetic cells.

IVM was also effective at slowing tumour growth in vivo in three mouse models of leukaemia [63], suggesting promise as a cancer chemotherapeutic.
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Significant clinical improvement was achieved with IVM treatment in a murine model of atopic dermatitis, with a reduction in T cell activation, proliferation, and cytokine production.
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In diabetic mice, IVM reduces serum glucose and cholesterol levels and improves insulin sensitivity through activation of FXR, suggesting potential as a novel diabetic therapy.
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IVM has also shown promise in the treatment of certain viral pathogens....Susceptible flaviviruses include those causing yellow fever, dengue, West Nile virus and tick borne encephalitis, and a patent application has been submitted for off-label antiflavivirus therapy in humans
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IVM has well established efficacy against a wide range of arthropods and may have potential in breaking transmission of human disease through vector control. IVM given to local cattle has been shown to reduce the survival and fecundity of the tsetse fly Glossina palpalis gambiensis that transmits animal and human trypanosomiasis (sleeping sickness) in sub-Saharan Africa... IVM ingested with host blood (modelled on plasma concentrations after a standard oral dose of 150 μg/kg) was found to reduce survival and blood feeding of Anopheles gambiae, the mosquito that transmits Plasmodium falciparum malaria [75]. The authors of that study suggested that an increased frequency of IVM treatment could break the cycle of malaria transmission, but highlighted the importance of field conditions and the potential development of resistance. Interestingly, different mosquito species are not uniformly susceptible to IVM. Aedes aegypti, the mosquito vector of yellow fever, dengue, and Zika, was not affected at IVM concentrations relevant to those in human blood following standard dosage, although survival and fecundity was affected at higher doses 75, 76. Furthermore, different strains of A. aegypti varied by approximately threefold in their adult survival rate after IVM ingestion, although the egg hatch rate varied to a lesser extent between strains and was not correlated to adult survival rate. This finding led the authors to speculate that IVM might affect mosquito survival and fecundity through different pathways
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Dosing

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The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.*
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This post is not intended to provide medical advice nor does it suggest making medical decisions that are done without the supervision of a doctor. Seek medical attention from a medical professional if you are not in good health.

For oral dosage form (tablets):
For river blindness:
Adults and teenagers—Dose is based on body weight and must be determined by your doctor. The usual dose is 150 micrograms (mcg) per kilogram (kg) (68 mcg per pound) of body weight as a single dose. The treatment may be repeated every three to twelve months.
Children—Dose is based on body weight and must be determined by your doctor. For children weighing 15 kg (33 pounds) or more, the usual dose is 150 mcg per kg (68 mcg per pound) of body weight as a single dose. If necessary, the treatment may be repeated every three to twelve months. For children weighing less than 15 kg, use and dose must be determined by your doctor.

For strongyloidiasis:
Adults and teenagers—Dose is based on body weight and must be determined by your doctor. The usual dose is 200 micrograms (mcg) per kilogram (kg) (91 mcg per pound) of body weight as a single dose. Additional doses usually are not needed.
Children—Dose is based on body weight and must be determined by your doctor. For children weighing 15 kg (33 pounds) or more, the usual dose is 200 mcg per kg (91 mcg per pound) of body weight as a single dose. For children weighing less than 15 kg, use and dose must be determined by your doctor.
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Further Information Regarding Dosing with Specific Parasite Species.

https://www.drugs.com/dosage/ivermectin.html

Safety of high-dose ivermectin

A descriptive analysis of these clinical trials for a variety of indications showed no difference in the severity of the adverse events between standard (up to 400 μg/kg) and higher doses of ivermectin. Organ system involvement only showed an increase in ocular events in the higher-dose group in one trial for the treatment of onchocerciasis, all of them transient and mild to moderate in intensity…
Although within this review the safety of high-dose ivermectin appears to be comparable to standard doses, there are not enough data to support a recommendation for its use in higher-than-approved doses.
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How to use Ivermectin

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Take this medication by mouth with a full glass of water (8 ounces or 240 milliliters) on an empty stomach at least 1 hour before a meal. Ivermectin is usually taken as a single dose or series of doses, or as directed by your doctor.
Dosage is based on your weight, medical condition, and response to treatment.
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Side Effects

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Headache, dizziness, muscle pain, nausea, or diarrhea may occur. If you are being treated for "river blindness" (onchocerciasis), you may experience reactions to the dying parasites during the first 4 days of treatment, including joint pain, tender/swollen lymph nodes, eye swelling/redness/pain, weakness, vision changes, itching, rash, and fever. If any of these effects persist or worsen, Tell your doctor or pharmacist promptly.
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Tell your doctor right away if any of these rare but very serious side effects occur: neck/back pain, swelling face/arms/hands/feet, chest pain, fast heartbeat, confusion, seizures, loss of consciousness.
A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
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Precautions

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Before taking ivermectin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems.
If you have traveled or lived in West or Central Africa, you may be infected with certain parasites (such as Loa loa, African trypanosomiasis) that could cause problems with ivermectin treatment. These effects could rarely result in serious (possibly fatal) effects on the brain (such as encephalopathy). Consult your doctor for more information.
This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
If you have a weakened immune system (such as due to HIV infection), you may need repeat treatments with this medicine. Talk to your doctor for more details.
During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.
Ivermectin passes into breast milk. Though there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.
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Interactions

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Some of the products that may interact with this drug include: barbiturates (such as phenobarbital, butalbital), benzodiazepines (such as clonazepam, lorazepam), sodium oxybate (GHB), valproic acid.
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Warfarin Interactions with Ivermectin

Ivermectin has been shown, in vitro, to antagonize the same vitamin K–dependent clotting factors that warfarin does (II, VII, IX, and X).
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Drug interactions of Stromectol(Ivermectin) include warfarin because Stromectol can increase risks of bleeding and bruising when co-administered with warfarin.
[Source](https://www.medicinenet.com/side_effects_of_ivermectin-oral/side-effects.htm

Ivermectin and Covid-19

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Currently, as of July 7th, 2021, Ivermectin is gaining lots of attention worldwide as a possible therapeutic in the defense of Covid-19, the disease caused by the coronavirus.

Timeline of Ivermectin's use with Convid-19. April 2020-March 2021

https://www.researchgate.net/publication/350610718_A_Timeline_of_Ivermectin-Related_Events_in_the_COVID-19_Pandemic_April_3_2021

Random news articles using the search term "Covid-19 Ivermectin"

Controversy

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Ivermectin, as of July 7th, 2021, is not recommended to be used as a Covid-19 therapeutic treatment by the FDA, CDC and WHO and other worldwide health organizations that worldwide governments implement the guidelines from.

The FDA

FDA has not approved ivermectin for use in treating or preventing COVID-19 in humans. Ivermectin tablets are approved at very specific doses for some parasitic worms, and there are topical (on the skin) formulations for head lice and skin conditions like rosacea. Ivermectin is not an anti-viral (a drug for treating viruses).
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The WHO

The current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive. Until more data is available, WHO recommends that the drug only be used within clinical trials.
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