Ivermectin – action, use, indications, dosage, side effects

Proven content

Ivermectin is a substance used mainly in the treatment of parasitic diseases in humans and animals and in the treatment of onchocercosis (river blindness) and topical treatment of rosacea. With the outbreak of the COVID-19 pandemic, ivermectin was tested for a preparation effective in the treatment of SARS-CoV-2 infection.

Ivermectin – what is it?

Ivermectin is a drug used to treat a parasitic infection. In humans, these include head lice, scabies, river blindness (onchocercosis), nematodes, whipworms, ascariasis and filariasis. In veterinary medicine, ivermectin is used, inter alia, in the prevention and treatment of heartworm and mites. Ivermectin acts through multiple mechanisms of action which lead to the death of the target parasites; it can be taken orally or applied to the skin for ectoparasites. This substance belongs to the avermectin family of drugs.

Ivermectin was discovered in 1975 and entered medical use in 1981. The drug is on the World Health Organization’s List of Essential Medicines.

During the COVID-19 pandemic, misinformation was widespread claiming that ivermectin is beneficial for the treatment and prevention of COVID-19. Such claims are not supported by credible scientific evidence. It should be added that research on the use of ivermectin is ongoing, and many major health organizations, including the Food and Drug Administration, the US Centers for Disease Control and Prevention, (CDC), the European Medicines Agency, and the World Health Organization, have concluded that ivermectin is not approved or approved for the treatment of COVID-19.

See also: Treating one parasitic infection can worsen the symptoms of another

Ivermectin – action

Ivermectin and related drugs work by interfering with the nerve and muscle function of parasites. The drug binds to glutamate-gated chloride channels common to nerve and muscle cells in invertebrates. Binding opens channels, which increases the flow of chloride ions and hyperpolarises cell membranes, paralyzing and killing invertebrates.

Ivermectin is safe for mammals (at normal therapeutic doses used to treat parasitic infections) because mammalian glutamate-gated chloride channels are found only in the brain and spinal cord: disease-causing avermectins do not normally cross the blood-brain barrier and are unlikely to bind to other mammalian channels gated with messengers (ionotropic receptors).

See also: The secret of the tight blood-brain barrier

Ivermectin – application

Ivermectin is used to treat human diseases caused by roundworms and ectoparasites.

Ivermectin and parasitic infections

In river blindness (onchocercosis) and lymphatic filariasis, ivermectin is usually administered to all members of the affected community. For river blindness, a single oral dose of ivermectin (150 micrograms per kilogram body weight) cleans the body of worm larvae Onchocerca volvulus for several months, preventing disease transmission and progression.

Adult worms survive in the skin and eventually regenerate, which leads to the reappearance of the larvae. To counteract this, ivermectin is administered at least once a year for the 10-15 years of life of adult worms. For lymphatic filariasis, oral ivermectin (200 micrograms per kilogram body weight) is part of an annual combination therapy: ivermectin, diethylcarbamazine citrate, and albendazole in areas without onchocercosis; and ivermectin and albendazole at sites of onchocercosis.

The World Health Organization (WHO) considers ivermectin to be the drug of choice for eel. Most cases are treated with two daily doses of oral ivermectin (200 µg per kg body weight), while severe infections are treated with ivermectin for five to seven days. Ivermectin is also the primary drug for infections mansonella ozzardi and in the case of migrating cutaneous larvae syndrome.

The US Centers for Disease Control and Prevention (CDC) recommends ivermectin, albendazole, or mebendazole for the treatment of ascariasis. Ivermectin is sometimes added to albendazole or mebendazole to treat whipworms and is considered a second line treatment for gnatostomyosis.

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Ivermectin and mites and insects

Ivermectin is also used to treat infections with parasitic arthropods. Scabies – mite infestation Sarcopts scabiei – is most often treated with topical permethrin or oral ivermectin. In most cases of scabies, ivermectin is used in a two-dose schedule: the first dose kills the active mites but not their eggs. The eggs hatch over the next week and the second dose kills the newly hatched mites.

For severe scabies, the US Centers for Disease Control and Prevention (CDC) recommends up to seven doses of ivermectin a month, along with a topical antiparasitic agent. Both head lice (head lice) and pubic lice (pubic lice) can be treated with oral ivermectin, ivermectin fluid applied directly to the affected area. Ivermectin is also used to treat rosacea and chronic blepharitis (blepharitis) which can be caused or exacerbated by Demodex folliculorum.

Ivermectin – dosage

In Poland, ivermectin is applied topically to the skin, and its dose depends on the given disease and the patient’s weight. Ivermectin is applied in a thin layer to the affected skin, once a day. Treatment should not exceed 4 months.

Ivermectin – contraindications

Ivermectin is contraindicated in children under five or those weighing less than 15 kilograms, and people with liver or kidney disease. The drug is excreted in very low concentrations into breast milk. However, it is unclear whether ivermectin is safe during pregnancy.

See also: Mother’s milk from a pediatrician’s perspective – truths and myths

Ivermectin – side effects

Side effects with ivermectin are quite rare and include fever, itching and skin rash when taken by mouth; and redness of the eyes, dry skin, and burning skin when applied topically to head lice. It is not known if the drug is safe for use during pregnancy, but it can possibly be used while breastfeeding.

Ivermectin is considered to be relatively free of toxicity at standard doses (approximately 300 µg / kg). Although the side effects of ivermectin are rare, serious adverse events are more common in people with a very high load of Loa loa larvae in their blood (loaza). Those who have more than 30 microfilariae per milliliter of blood risk inflammation and capillary blockage due to the rapid death of microfilariae after ivermectin treatment. For ivermectin, there are concerns regarding neurotoxicity following major overdose, which in most mammal species can manifest as CNS depression, ataxia, coma and even death as would be expected with enhancement of the inhibitory chloride channels.

Since drugs that inhibit the enzyme CYP3A4 also frequently inhibit P-gp transport, there is a risk of increased absorption across the blood-brain barrier when ivermectin is co-administered with other inhibitors of CYP3A4. These drugs include statins, HIV protease inhibitors, many calcium channel blockers, lidocaine, benzodiazepines, and glucocorticoids such as dexamethasone.

During usual therapy, ivermectin may cause a slight elevation of transaminases. In rare cases, it can cause mild clinical liver disease.

Although ivermectin has also been tested for use in COVID-19, and although it has some ability to inhibit SARS-CoV-2 in vitro, it has been found that achieving 50% inhibition in vitro requires an estimated oral dose of 7,0 mg / kg, sufficiently high. to consider it ivermectin poisoning. Despite insufficient data to demonstrate any safe and effective dosing regimen for ivermectin in COVID-19, doses have been taken well in excess of the FDA approved doses, prompting the CDC to issue an overdose warning including nausea, vomiting, diarrhea, hypotension, and depressed consciousness , confusion, blurred vision, visual hallucinations, loss of coordination and balance, seizures, coma and death.

See also: Poisoning with drugs from the group of calcium channel blockers

Ivermectin and tropical diseases

Ivermectin is being investigated as a potential antiviral agent against Chikungunya virus and yellow fever. In the case of chikungunya fever, ivermectin had a wide margin of safety as an antiviral agent.

Ivermectin is also of interest in preventing malaria because it is toxic to both the protozoa themselves malaria plasmodiumand mosquitoes that carry it. It was not possible to demonstrate a direct effect on the malaria parasites in the experimental infection of volunteers Plasmodium falciparum. The use of ivermectin at the higher doses necessary to control malaria is likely safe, although large clinical trials have not yet been conducted to ultimately establish the efficacy or safety of ivermectin in the prevention or treatment of malaria. Massive administration of ivermectin drugs to treat and prevent nematode infestation is effective in eliminating malaria-carrying mosquitoes, thereby reducing infection with residual malaria parasites.

One alternative to ivermectin is moxidectin, which has been approved by the Food and Drug Administration for use in people with river blindness. Moxidectin has a longer half-life than ivermectin and may eventually replace ivermectin because it is a more potent microfilaricide, but additional clinical studies with long-term follow-up are needed to determine if moxidectin is safe and effective in treating nematode infections in children and women of childbearing age.

There is also preliminary evidence that ivermectin kills bedbugs, but such use may require prolonged treatment.

See also: New viruses in Europe

Ivermectin to COVID-19

Ivermectin has antiviral activity against several distinct single-stranded RNA viruses, including SARS-CoV-2. Later studies showed that ivermectin could inhibit SARS-CoV-2 replication in monkey kidney cell culture with an IC50 of 2,2-2,8 µM. However, based on this information, doses well higher than the maximum approved or safely achievable for human use would be required to obtain an antiviral effect. In addition to practical difficulties, such high doses are not covered by the current human drug approvals and would be toxic, since the mechanism of antiviral action is believed to be suppression of the host cellular process, in particular inhibition of nuclear transport by α / β1 importin.

Much of the research on ivermectin for COVID-19 has severe methodological limitations, resulting in very low certainty of evidence. Several publications that talked about the effectiveness of ivermectin in treating COVID-19 have been withdrawn due to errors, unverifiable data and ethical concerns, including misleading online meta-analyzes with substandard methods. As a result, several organizations publicly stated that there was insufficient evidence of ivermectin’s effectiveness in preventing or treating COVID-19 and advised against using the drug for unapproved purposes.

In February 2021, Merck & Co., the makers of the drug, issued a statement stating that there was no evidence that ivermectin was effective against COVID-19 and that attempting to use it could be dangerous. After reviewing the evidence on ivermectin, the European Medicines Agency (EMA) advised against its use in the prevention or treatment of COVID-19, claiming that “the available data do not support its use in COVID-19 outside of well-designed clinical trials”.

The US National Institutes of Health’s COVID-19 treatment guidelines state that there is insufficient evidence for the use of ivermectin to make a recommendation for or against its use. In the UK, a national advisory panel on COVID-19 therapies found that ivermectin’s evidence base and reliability as a treatment for COVID-19 were insufficient to continue further research. Ivermectin is not approved by the US Food and Drug Administration (FDA) for use in the treatment of any viral disease and is not approved for use in the treatment of COVID-19 in the European Union. The WHO also concluded that ivermectin should not be used to treat COVID-19, except in clinical trials.

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