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Pronunciation | /ˌaɪvərˈmɛktɪn/ , EYE-vər-MEK-tin |
Trade names | Stromectol, others |
Other names | MK-933 |
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MedlinePlus | a607069 |
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Routes of administration | By mouth, topical |
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Bioavailability | not determined |
Protein binding | 93% |
Metabolism | Liver (CYP450) |
Elimination half-life | 38.9 ± 20.8 h [6] |
Excretion | Feces; <1% urine |
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ECHA InfoCard | 100.067.738 |
Chemical and physical data | |
Formula | C 48H 74O 14(22,23-dihydroavermectin B1a) C 47H 72O 14(22,23-dihydroavermectin B1b) |
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Ivermectin is an antiparasitic drug. [7] After its discovery in 1975, [8] its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. [9] Approved for human use in 1987, [10] it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. [9] [11] [12] [13] It works through many mechanisms to kill the targeted parasites, [11] and can be taken by mouth, or applied to the skin for external infestations. [11] [14] It belongs to the avermectin family of medications. [11]
William Campbell and Satoshi Ōmura were awarded the 2015 Nobel Prize in Physiology or Medicine for its discovery and applications. [15] It is on the World Health Organization's List of Essential Medicines, [16] [17] and is approved by the U.S. Food and Drug Administration as an antiparasitic agent. [18] In 2022, it was the 314th most commonly prescribed medication in the United States, with more than 200,000 prescriptions. [19] It is available as a generic medicine. [20] [21]
Misinformation has been widely spread claiming that ivermectin is beneficial for treating and preventing COVID-19. [22] [23] Such claims are not backed by credible scientific evidence. [24] [25] [26] Multiple major health organizations, including the U.S. Food and Drug Administration, [27] the U.S. Centers for Disease Control and Prevention, [28] the European Medicines Agency, [29] and the World Health Organization have advised that ivermectin is not recommended for the treatment of COVID-19. [25] [30]
Ivermectin is used to treat human diseases caused by roundworms and a wide variety of external parasites. [31]
For river blindness (onchocerciasis) and lymphatic filariasis, ivermectin is typically given as part of mass drug administration campaigns that distribute the drug to all members of a community affected by the disease. [32] Adult worms survive in the skin and eventually recover to produce larval worms again; to keep the worms at bay, ivermectin is given at least once per year for the 10–15-year lifespan of the adult worms. [33]
The World Health Organization (WHO) considers ivermectin the drug of choice for strongyloidiasis. [34] Ivermectin is also the primary treatment for Mansonella ozzardi and cutaneous larva migrans. [35] [36] The U.S. Centers for Disease Control and Prevention (CDC) recommends ivermectin, albendazole, or mebendazole as treatments for ascariasis. [37] [note 1] Ivermectin is sometimes added to albendazole or mebendazole for whipworm treatment, and is considered a second-line treatment for gnathostomiasis. [36] [41]
Ivermectin is also used to treat infection with parasitic arthropods. Scabies – infestation with the mite Sarcoptes scabiei – is most commonly treated with topical permethrin or oral ivermectin. A single application of permethrin is more efficacious than a single treatment of ivermectin[ citation needed ]. For most scabies cases, ivermectin is used in a two-dose regimen: the first dose kills the active mites, but not their eggs. Over the next week, the eggs hatch, and a second dose kills the newly hatched mites. [42] [43] The two-dose regimen of ivermectin has similar efficacy to the single dose permethrin treatment. Ivermectin is, however, more effective than permethrin when used in the mass treatment of endemic scabies. [44]
For severe "crusted scabies", where the parasite burden is orders of magnitude higher than usual, the U.S. Centers for Disease Control and Prevention (CDC) recommends up to seven doses of ivermectin over the course of a month, along with a topical antiparasitic. [43] Both head lice and pubic lice can be treated with oral ivermectin, an ivermectin lotion applied directly to the affected area, or various other insecticides. [45] [46] Ivermectin is also used to treat rosacea and blepharitis, both of which can be caused or exacerbated by Demodex folliculorum mites. [47] [48]
The only absolute contraindication to the use of ivermectin is hypersensitivity to the active ingredient or any component of the formulation. [49] [50] In children under the age of five or those who weigh less than 15 kilograms (33 pounds), [51] there is limited data regarding the efficacy or safety of ivermectin, though the available data demonstrate few adverse effects. [52] However, the American Academy of Pediatrics cautions against use of ivermectin in such patients, as the blood-brain barrier is less developed, and thus there may be an increased risk of particular CNS side effects such as encephalopathy, ataxia, coma, or death. [53] The American Academy of Family Physicians also recommends against use in these patients, given a lack of sufficient data to prove drug safety. [54] Ivermectin is secreted in very low concentration in breast milk. [55] It remains unclear if ivermectin is safe during pregnancy. [56]
Side effects, although uncommon, include fever, itching, and skin rash when taken by mouth; [11] and red eyes, dry skin, and burning skin when used topically for head lice. [57] It is unclear if the drug is safe for use during pregnancy, but it is probably acceptable for use during breastfeeding. [58]
Ivermectin is considered relatively free of toxicity in standard doses (around 300 μg/kg). [59] [60] Based on the data drug safety sheet for ivermectin, [a] side effects are uncommon. However, serious adverse events following ivermectin treatment are more common in people with very high burdens of larval Loa loa worms in their blood. [61] Those who have over 30,000 microfilaria per milliliter of blood risk inflammation and capillary blockage due to the rapid death of the microfilaria following ivermectin treatment. [61]
One concern is neurotoxicity after large overdoses, which in most mammalian species may manifest as central nervous system depression, [62] ataxia, coma, and even death, [63] [64] as might be expected from potentiation of inhibitory chloride channels. [65]
Since drugs that inhibit the enzyme CYP3A4 often also inhibit P-glycoprotein transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include statins, HIV protease inhibitors, many calcium channel blockers, lidocaine, the benzodiazepines, and glucocorticoids such as dexamethasone. [66]
During a typical treatment course, ivermectin can cause minor aminotransferase elevations. In rare cases it can cause mild clinically apparent liver disease. [67]
To provide context for the dosing and toxicity ranges, the LD50 of ivermectin in mice is 25 mg/kg (oral), and 80 mg/kg in dogs, corresponding to an approximated human-equivalent dose LD50 range of 2.02–43.24 mg/kg, [68] which is far more than its FDA-approved usage (a single dose of 0.150–0.200 mg/kg to be used for specific parasitic infections). [3] While ivermectin has also been studied for use in COVID-19, and while it has some ability to inhibit SARS-CoV-2 in vitro, achieving 50% inhibition in vitro was found to require an estimated oral dose of 7.0 mg/kg (or 35x the maximum FDA-approved dosage), [69] high enough to be considered ivermectin poisoning. [68] Despite insufficient data to show any safe and effective dosing regimen for ivermectin in COVID-19, doses have been taken far more than FDA-approved dosing, leading the CDC to issue a warning of overdose symptoms including nausea, vomiting, diarrhea, hypotension, decreased level of consciousness, confusion, blurred vision, visual hallucinations, loss of coordination and balance, seizures, coma, and death. The CDC advises against consuming doses intended for livestock or doses intended for external use and warns that increasing misuse of ivermectin-containing products is increasing harmful overdoses. [70]
Ivermectin and its related drugs act by interfering with the nerve and muscle functions of helminths and insects. [71] The drug binds to glutamate-gated chloride channels common to invertebrate nerve and muscle cells. [72] The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, [71] paralyzing and killing the invertebrate. [72] Ivermectin is safe for mammals (at the normal therapeutic doses used to cure parasite infections) because mammalian glutamate-gated chloride channels only occur in the brain and spinal cord: the causative avermectins usually do not cross the blood–brain barrier, and are unlikely to bind to other mammalian ligand-gated channels. [72]
Ivermectin can be given by mouth, topically, or via injection. Oral doses are absorbed into systemic circulation; the alcoholic solution form is more orally available than tablet and capsule forms. Ivermectin is widely distributed in the body. [73]
Ivermectin does not readily cross the blood-brain barrier of mammals due to the presence of P-glycoprotein (the MDR1 gene mutation affects the function of this protein). [74] Crossing may still become significant if ivermectin is given at high doses, in which case brain levels peak 2–5 hours after administration. In contrast to mammals, ivermectin can cross the blood-brain barrier in tortoises, often with fatal consequences. [75]
Ivermectin is metabolized into eight different products by human CYP3A4, two of which (M1, M2) remain toxic to mosquitos. M1 and M2 also have longer elimination half-lives of about 55 hours. CYP3A5 produces a ninth metabolite. [6]
Fermentation of Streptomyces avermitilis yields eight closely related avermectin homologues, of which B1a and B1b form the bulk of the products isolated. In a separate chemical step, the mixture is hydrogenated to give ivermectin, which is an approximately 80:20 mixture of the two 22,23-dihydroavermectin compounds. [76] [77] [7]
Ivermectin is a macrocyclical lactone. [78]
The avermectin family of compounds was discovered by Satoshi Ōmura of Kitasato University and William Campbell of Merck. [7] In 1970, Ōmura isolated a strain of Streptomyces avermitilis from woodland soil near a golf course along the southeast coast of Honshu, Japan. [7] Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm Heligmosomoides polygyrus . [7] Campbell isolated the active compounds from the bacterial culture, naming them "avermectins" and the bacterium Streptomyces avermitilis for the compounds' ability to clear mice of worms (in Latin: a 'without', vermis 'worms'). [7] Of the various avermectins, Campbell's group found the compound "avermectin B1" to be the most potent when taken orally. [7] They synthesized modified forms of avermectin B1 to improve its pharmaceutical properties, eventually choosing a mixture of at least 80% 22,23-dihydroavermectin B1a and up to 20% 22,23-dihydroavermectin B1b, a combination they called "ivermectin". [7] [79]
The discovery of ivermectin has been described as a combination of "chance and choice." Merck was looking for a broad-spectrum anthelmintic, which ivermectin is; however, Campbell noted that they "...also found a broad-spectrum agent for the control of ectoparasitic insects and mites." [80]
Merck began marketing ivermectin as a veterinary antiparasitic in 1981. [7] By 1986, ivermectin was registered for use in 46 countries and was administered massively to cattle, sheep, and other animals. [81] By the late 1980s, ivermectin was the bestselling veterinary medicine in the world. [7] Following its blockbuster success as a veterinary antiparasitic, another Merck scientist, Mohamed Aziz, collaborated with the World Health Organization to test the safety and efficacy of ivermectin against onchocerciasis in humans. [10] They found it to be highly safe and effective, [82] triggering Merck to register ivermectin for human use as "Mectizan" in France in 1987. [10] A year later, Merck CEO Roy Vagelos agreed that Merck would donate all ivermectin needed to eradicate river blindness. [10] In 1998, that donation would be expanded to include ivermectin used to treat lymphatic filariasis. [10]
Ivermectin earned the title of "wonder drug" for the treatment of nematodes and arthropod parasites. [83] Ivermectin has been used safely by hundreds of millions of people to treat river blindness and lymphatic filariasis. [7]
Half of the 2015 Nobel Prize in Physiology or Medicine was awarded jointly to Campbell and Ōmura for discovering ivermectin, "the derivatives of which have radically lowered the incidence of river blindness and lymphatic filariasis, as well as showing efficacy against an expanding number of other parasitic diseases". [15] [84]
Early in the COVID-19 pandemic, laboratory research suggested ivermectin might have a role in preventing or treating COVID-19. [85] Online misinformation campaigns and advocacy boosted the drug's profile among the public. While scientists and physicians largely remained skeptical, some nations adopted ivermectin as part of their pandemic-control efforts. Some people, desperate to use ivermectin without a prescription, took veterinary preparations, which led to shortages of supplies of ivermectin for animal treatment. The FDA responded to this situation by saying "You are not a horse" in a Tweet to draw attention to the issue, for which they were later sued. [86] [87]
Subsequent research failed to confirm the utility of ivermectin for COVID-19, [88] [89] and in 2021 it emerged that many of the studies demonstrating benefit were faulty, misleading, or fraudulent. [90] [91] Nevertheless, misinformation about ivermectin continued to be propagated on social media and the drug remained a cause célèbre for anti-vaccinationists and conspiracy theorists. [92]The initial price proposed by Merck in 1987 was US$ 6 per treatment, which was unaffordable for patients who most needed ivermectin. [93] The company donated hundreds of millions of courses of treatments since 1988 in more than 30 countries. [93] Between 1995 and 2010, using donated ivermectin to prevent river blindness, the program is estimated to have prevented seven million years of disability at a cost of US$ 257 million. [94]
Ivermectin is considered an inexpensive drug. [95] As of 2019, ivermectin tablets (Stromectol) in the United States were the least expensive treatment option for lice in children at approximately US$ 9.30, while Sklice, an ivermectin lotion, cost around US$ 300 for 120 mL (4 US fl oz). [96]
As of 2019 [update] , the cost effectiveness of treating scabies and lice with ivermectin has not been studied. [97] [98]
It is sold under the brand names Heartgard, Sklice [99] and Stromectol [3] in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT [100] in Nepal by Alive Pharmaceutical and Ivexterm in Mexico by Valeant Pharmaceuticals International. In Southeast Asian countries, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. The formulation for rosacea treatment is sold under the brand name Soolantra. [4] While in development, it was assigned the code MK-933 by Merck. [101]
Ivermectin has been researched in laboratory animals, as a potential treatment for trichinosis [32] and trypanosomiasis. [102]
Ivermectin has also been tested on zebrafish infected with Pseudocapillaria tomentosa . [103]
Ivermectin is also of interest in the prevention of malaria, as it is toxic to both the malaria plasmodium itself and the mosquitos that carry it. [104] [105] A direct effect on malaria parasites could not be shown in an experimental infection of volunteers with Plasmodium falciparum . [106] Use of ivermectin at higher doses necessary to control malaria is probably safe, though large clinical trials have not yet been done to definitively establish the efficacy or safety of ivermectin for prophylaxis or treatment of malaria. [107] [59] Mass drug administration of a population with ivermectin to treat and prevent nematode infestation is effective for eliminating malaria-bearing mosquitos and thereby potentially reducing infection with residual malaria parasites. [108] Whilst effective in killing malaria-bearing mosquitos, a 2021 Cochrane review found that, to date, the evidence shows no significant impact on reducing incidence of malaria transmission from the community administration of ivermectin. [107]
One alternative to ivermectin is moxidectin, which has been approved by the Food and Drug Administration for use in people with river blindness. [109] Moxidectin has a longer half-life than ivermectin and may eventually supplant ivermectin as it is a more potent microfilaricide, but there is a need for additional clinical trials, with long-term follow-up, to assess whether moxidectin is safe and effective for treatment of nematode infection in children and women of childbearing potential. [110] [111]
There is tentative evidence that ivermectin kills bedbugs, as part of integrated pest management for bedbug infestations. [112] [113] [114] However, such use may require a prolonged course of treatment which is of unclear safety. [115]
In 2013, ivermectin was demonstrated as a novel ligand of the farnesoid X receptor, [116] [117] a therapeutic target for nonalcoholic fatty liver disease (NAFLD). [118]
During the COVID-19 pandemic, ivermectin was researched for possible utility in preventing and treating COVID-19, but no good evidence of benefit was found. [119] [120]
Ivermectin is routinely used to control parasitic worms in the gastrointestinal tract of ruminant animals. These parasites normally enter the animal when it is grazing, pass the bowel, and set and mature in the intestines, after which they produce eggs that leave the animal via its droppings and can infest new pastures. Ivermectin is only effective in killing some of these parasites, because of an increase in anthelmintic resistance. [121] This resistance has arisen from the persistent use of the same anthelmintic drugs for the past 40 years. [122] [123] Additionally, the use of Ivermectin for livestock has a profound impact on dung beetles, such as T. lusitanicus, as it can lead to acute toxicity within these insects. [124]
In dogs, ivermectin is routinely used as prophylaxis against heartworm. [125] Dogs with defects in the P-glycoprotein gene (MDR1), often collie-like herding dogs, can be severely poisoned by ivermectin. The mnemonic "white feet, don't treat" refers to Scotch collies that are vulnerable to ivermectin. [126] Some other dog breeds (especially the Rough Collie, the Smooth Collie, the Shetland Sheepdog, and the Australian Shepherd), also have a high incidence of mutation within the MDR1 gene (coding for P-glycoprotein) and are sensitive to the toxic effects of ivermectin. [127] [128] For dogs, the insecticide spinosad may have the effect of increasing the toxicity of ivermectin. [129] [130]
A 0.01% ivermectin topical preparation for treating ear mites in cats is available. [131] Clinical evidence suggests 7-week-old kittens are susceptible to ivermectin toxicity. [132]
Ivermectin is sometimes used as an acaricide in reptiles, both by injection and as a diluted spray. While this works well in some cases, care must be taken, as several species of reptiles are very sensitive to ivermectin. Use in turtles is particularly contraindicated. [133]
A characteristic of the antinematodal action of ivermectin is its potency: for instance, to combat Dirofilaria immitis in dogs, ivermectin is effective at 0.001 milligram per kilogram of body weight when administered orally. [79]
Malaria is a mosquito-borne infectious disease that affects vertebrates and Anopheles mosquitoes. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquito vector is itself harmed by Plasmodium infections, causing reduced lifespan.
Scabies is a contagious human skin infestation by the tiny (0.2–0.45 mm) mite Sarcoptes scabiei, variety hominis. The word is from Latin: scabere, lit. 'to scratch'. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin. In a first-ever infection, the infected person usually develops symptoms within two to six weeks. During a second infection, symptoms may begin within 24 hours. These symptoms can be present across most of the body or just certain areas such as the wrists, between fingers, or along the waistline. The head may be affected, but this is typically only in young children. The itch is often worse at night. Scratching may cause skin breakdown and an additional bacterial infection in the skin.
Trichuriasis, also known as whipworm infection, is an infection by the parasitic worm Trichuris trichiura (whipworm). If infection is only with a few worms, there are often no symptoms. In those who are infected with many worms, there may be abdominal pain, fatigue and diarrhea. The diarrhea sometimes contains blood. Infections in children may cause poor intellectual and physical development. Low red blood cell levels may occur due to loss of blood.
Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm Onchocerca volvulus. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindness due to infection, after trachoma.
Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto outer clothing or mosquito nets to kill the insects that touch them.
Doxycycline is a broad-spectrum antibiotic of the tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis. It is also used to prevent malaria. Doxycycline may be taken by mouth or by injection into a vein.
Mange is a type of skin disease caused by parasitic mites. Because various species of mites also infect plants, birds and reptiles, the term "mange", or colloquially "the mange", suggesting poor condition of the skin and fur due to the infection, is sometimes reserved for pathological mite-infestation of nonhuman mammals. Thus, mange includes mite-associated skin disease in domestic mammals, in livestock, and in wild mammals. Severe mange caused by mites has been observed in wild bears. Since mites belong to the arachnid subclass Acari, another term for mite infestation is acariasis.
Abamectin (also called avermectin B1) is a widely used insecticide and anthelmintic. Abamectin, is a member of the avermectin family and is a natural fermentation product of soil dwelling actinomycete Streptomyces avermitilis. Abamectin differs from ivermectin, the popular member of the avermectin family, by a double bond between carbons 22 and 25. Fermentation of Streptomyces avermitilis yields eight closely related avermectin homologs, with the B1a and B1b forms comprising the majority of the fermentation. The non-proprietary name, abamectin, refers to a mixture of B1a (~80%) and B1b (~20%). Out of all the avermectins, abamectin is the only one that is used both in agriculture and pharmaceuticals.
Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, by mouth, and by rectum.
Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of haeme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. While it has not been formally studied in pregnancy, it appears safe. It was studied to treat COVID-19 early in the pandemic, but these studies were largely halted in the summer of 2020, and the NIH does not recommend its use for this purpose. It is taken by mouth.
Primaquine is a medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used. It is an alternative treatment for Pneumocystis pneumonia together with clindamycin. It is taken by mouth.
Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disease, and giardia, among others. It is taken by mouth.
Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle, sheep and wombats. Moxidectin kills some of the most common internal and external parasites by selectively binding to a parasite's glutamate-gated chloride ion channels. These channels are vital to the function of invertebrate nerve and muscle cells; when moxidectin binds to the channels, it disrupts neurotransmission, resulting in paralysis and death of the parasite.
Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by mouth, often in the form of hydroxychloroquine sulfate.
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may also be called vermifuges or vermicides. Anthelmintics are used to treat people who are infected by helminths, a condition called helminthiasis. These drugs are also used to treat infected animals, particularly small ruminants such as goats and sheep.
William Cecil Campbell is an Irish-American microbiologist known for his work in discovering a novel therapy against infections caused by roundworms, for which he was jointly awarded the 2015 Nobel Prize in Physiology or Medicine. He helped to discover a class of drugs called avermectins, whose derivatives have been shown to have "extraordinary efficacy" in treating River blindness and Lymphatic filariasis, among other parasitic diseases affecting animals and humans. Campbell worked at the Merck Institute for Therapeutic Research 1957–1990, and has become a research fellow emeritus at Drew University.
Artesunate/pyronaridine, sold under the brand name Pyramax, is a fixed-dose combination medication for the treatment of malaria. It can be used for malaria of both the P. falciparum and P. vivax types. It combines artesunate and pyronaridine. It is taken by mouth.
Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.
Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases. Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19. Neither drug has been useful to prevent or treat SARS-CoV-2 infection. Administration of chloroquine or hydroxychloroquine to COVID-19 patients, either as monotherapies or in conjunction with azithromycin, has been associated with deleterious outcomes, such as QT prolongation. As of 2024, scientific evidence does not substantiate the efficacy of hydroxychloroquine, with or without the addition of azithromycin, in the therapeutic management of COVID-19.
Ivermectin is an antiparasitic drug that is well established for use in animals and people. The World Health Organization (WHO), the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA), and the Infectious Diseases Society of America (IDSA) all advise against using ivermectin in an attempt to treat or prevent COVID-19.
Ivermectin was a revelation. It had a broad spectrum of activity, and was highly efficacious, acting robustly at low doses against a wide variety of nematode, insect, and acarine parasites. It proved to be extremely effective against most common intestinal worms (except tapeworms), could be administered orally, topically or parentally, and showed no signs of cross-resistance with other commonly used anti-parasitic compounds.
Although relatively free from toxicity, ivermectin – when large overdoses are administered – may cross the blood–brain barrier, producing depressant effects on the CNS
Few hours after administration: nausea, vomiting, abdominal pain, salivation, tachycardia, hypotension, ataxia, pyramidal signs, binocular diplopia
You can also overdose on ivermectin, which can cause nausea, vomiting, diarrhea, hypotension (low blood pressure), allergic reactions (itching and hives), dizziness, ataxia (problems with balance), seizures, coma and even death.
Based on the reported neurotoxicity and metabolic pathway of IVM, caution should be taken to conduct clinical trial on its antiviral potentials. The GABA-gated chloride channels in the human nervous system might be a target for IVM, this is because the BBB in disease-patient might be weakened as a result of inflammation and other destructive processes, allowing IVM to cross the BBB and gain access to the CNS where it can elicit its neurotoxic effect
Ivermectin treatment is emerging as a potential ancillary measure.