Ivermectin

Last updated

Ivermectin
Ivermectin skeletal.svg
Ivermectin-B1a-from-xtal-3D-bs-17.png
Clinical data
Pronunciation /ˌaɪvərˈmɛktɪn/ , EYE-vər-MEK-tin
Trade names Stromectol, Soolantra, Sklice, others
Other namesMK-933
AHFS/Drugs.com
MedlinePlus a607069
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability not determined
Protein binding 93%
Metabolism Liver (CYP450)
Elimination half-life 18 hours
Excretion Feces; <1% urine
Identifiers
  • 22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.067.738 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C
48H
74O
14(22,23-dihydroavermectin B1a)
C
47H
72O
14(22,23-dihydroavermectin B1b)
Molar mass
  • 875.106 g·mol−1(22,23-dihydroavermectin B1a)
  • 861.079 g·mol−1(22,23-dihydroavermectin B1b)
3D model (JSmol)
    • CC[C@H](C)[C@@H]1[C@H](CC[C@@]2(O1)C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([C@H](/C=C/C=C/4\CO[C@H]5[C@@]4([C@@H](C=C([C@H]5O)C)C(=O)O3)O)C)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O[C@H]7C[C@@H]([C@H]([C@@H](O7)C)O)OC)OC)\C)C.C[C@H]1CC[C@]2(C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([C@H](/C=C/C=C/4\CO[C@H]5[C@@]4([C@@H](C=C([C@H]5O)C)C(=O)O3)O)C)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O[C@H]7C[C@@H]([C@H]([C@@H](O7)C)O)OC)OC)\C)O[C@@H]1C(C)C
    • InChI=1S/C48H74O14.C47H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18–34(45(50)57-33)47(31,44)51)58-38-21-36(53–10)43(30(8)56–38)59-37-20-35(52–9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+;25-,27-,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m00/s1 Yes check.svgY
    • Key:SPBDXSGPUHCETR-JFUDTMANSA-N Yes check.svgY
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    Ivermectin is an antiparasitic drug. [6] After its discovery in 1975, [7] its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. [8] Approved for human use in 1987, [9] it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. [8] [10] [11] [12] It works through many mechanisms to kill the targeted parasites, [10] and can be taken by mouth, or applied to the skin for external infestations. [10] [13] It belongs to the avermectin family of medications. [10]

    Contents

    William Campbell and Satoshi Ōmura won the 2015 Nobel Prize in Physiology or Medicine for its discovery and applications. [14] It is on the World Health Organization's List of Essential Medicines, [15] [16] and is approved by the U.S. Food and Drug Administration as an antiparasitic agent. [17] In 2021, it was the 341st most commonly prescribed medication in the United States, with more than 100,000 prescriptions. [18] It is available as a generic medicine. [19] [20]

    During the COVID-19 pandemic, misinformation has been widely spread claiming that ivermectin is beneficial for treating and preventing COVID-19. [21] [22] Such claims are not backed by credible scientific evidence. [23] [24] [25] Multiple major health organizations, including the U.S. Food and Drug Administration, [26] the U.S. Centers for Disease Control and Prevention, [27] the European Medicines Agency, [28] and the World Health Organization have stated that ivermectin is not authorized or approved to treat COVID-19. [24] [29]

    Medical uses

    Ivermectin is used to treat human diseases caused by roundworms and a wide variety of external parasites. [30]

    Worm infections

    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. [31] 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. [32]

    The World Health Organization (WHO) considers ivermectin the drug of choice for strongyloidiasis. [33] Ivermectin is also the primary treatment for Mansonella ozzardi and cutaneous larva migrans. [34] [35] The U.S. Centers for Disease Control and Prevention (CDC) recommends ivermectin, albendazole, or mebendazole as treatments for ascariasis. [36] [note 1] Ivermectin is sometimes added to albendazole or mebendazole for whipworm treatment, and is considered a second-line treatment for gnathostomiasis. [35] [40]

    Mites and insects

    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. For most scabies cases, ivermectin is used in a two dose regimen: a 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. [41] [42] 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. [43]

    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. [42] 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. [44] [45] Ivermectin is also used to treat rosacea and blepharitis, both of which can be caused or exacerbated by Demodex folliculorum mites. [46] [47]

    Contraindications

    The only absolute contraindication to the use of ivermectin is hypersensitivity to the active ingredient or any component of the formulation. [48] [49] In children under the age of five or those who weigh less than 15 kilograms (33 pounds), [50] there is limited data regarding the efficacy or safety of ivermectin, though the available data demonstrate few adverse effects. [51] 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. [52] The American Academy of Family Physicians also recommends against use in these patients, given a lack of sufficient data to prove drug safety. [53] Ivermectin is secreted in very low concentration in breast milk. [54] It remains unclear if ivermectin is safe during pregnancy. [55]

    Adverse effects

    Side effects, although uncommon, include fever, itching, and skin rash when taken by mouth; [10] and red eyes, dry skin, and burning skin when used topically for head lice. [56] It is unclear if the drug is safe for use during pregnancy, but it is probably acceptable for use during breastfeeding. [57]

    Ivermectin is considered relatively free of toxicity in standard doses (around 300 µg/kg). [58] [59] Based on the data drug safety sheet for ivermectin, [lower-alpha 1] 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. [60] 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. [60]

    One concern is neurotoxicity after large overdoses, which in most mammalian species may manifest as central nervous system depression, [61] ataxia, coma, and even death, [62] [63] as might be expected from potentiation of inhibitory chloride channels. [64]

    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. [65]

    During the course of a typical treatment, ivermectin can cause minor aminotransferase elevations. In rare cases it can cause mild clinically apparent liver disease. [66]

    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, [67] which is far in excess of 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), [68] high enough to be considered ivermectin poisoning. [67] Despite insufficient data to show any safe and effective dosing regimen for ivermectin in COVID-19, doses have been taken far in excess of 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 resulting in an increase in harmful overdoses. [69]

    Pharmacology

    Ivermectin (IVM) bound to a C. elegans GluClR. IVM molecules interact with a binding pocket formed by the transmembrane domains of adjacent GluClR subunits, "locking" the receptor in an activated (open) conformation that allows unrestricted passage of chloride (Cl-) ions into the cell. (The plasma membrane is represented as a blue-pink gradient.) From PDB: 3RHW . Ivermectin mechanism of action 3RHW.png
    Ivermectin (IVM) bound to a C. elegans GluClR. IVM molecules interact with a binding pocket formed by the transmembrane domains of adjacent GluClR subunits, "locking" the receptor in an activated (open) conformation that allows unrestricted passage of chloride (Cl−) ions into the cell. (The plasma membrane is represented as a blue–pink gradient.) From PDB: 3RHW ​.

    Mechanism of action

    Ivermectin and its related drugs act by interfering with the nerve and muscle functions of helminths and insects. [70] The drug binds to glutamate-gated chloride channels common to invertebrate nerve and muscle cells. [71] The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, [70] paralyzing and killing the invertebrate. [71] 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. [71]

    Pharmacokinetics

    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. [72]

    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). [73] 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. [74]

    Chemistry

    Avermectins produced by fermentation are the chemical starting point for ivermectin Avermectins.png
    Avermectins produced by fermentation are the chemical starting point for ivermectin

    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. [75] [76] [6]

    Ivermectin is a macrocyclical lactone. [77]

    History

    The avermectin family of compounds was discovered by Satoshi Ōmura of Kitasato University and William Campbell of Merck. [6] In 1970, Ōmura isolated a strain of Streptomyces avermitilis from woodland soil near a golf course along the south east coast of Honshu, Japan. [6] Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm Heligmosomoides polygyrus . [6] 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'). [6] Of the various avermectins, Campbell's group found the compound "avermectin B1" to be the most potent when taken orally. [6] 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". [6] [78]

    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 indeed; however, Campbell noted that they "...also found a broad-spectrum agent for the control of ectoparasitic insects and mites." [79]

    Merck began marketing ivermectin as a veterinary antiparasitic in 1981. [6] By 1986, ivermectin was registered for use in 46 countries and was administered massively to cattle, sheep and other animals. [80] By the late 1980s, ivermectin was the bestselling veterinary medicine in the world. [6] 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. [9] They found it to be highly safe and effective, [81] triggering Merck to register ivermectin for human use as "Mectizan" in France in 1987. [9] A year later, Merck CEO Roy Vagelos agreed that Merck would donate all ivermectin needed to eradicate river blindness. [9] In 1998, that donation would be expanded to include ivermectin used to treat lymphatic filariasis. [9]

    Ivermectin earned the title of "wonder drug" for the treatment of nematodes and arthropod parasites. [82] Ivermectin has been used safely by hundreds of millions of people to treat river blindness and lymphatic filariasis. [6]

    Half of the 2015 Nobel Prize in Physiology or Medicine was awarded jointly to Campbell and Ōmura for discovering avermectin, "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". [14] [83]

    Society and culture

    COVID-19 misinformation

    These paragraphs are an excerpt from Ivermectin during the COVID-19 pandemic.[ edit ]

    Early in the COVID-19 pandemic, laboratory research suggested ivermectin might have a role in preventing or treating COVID-19. [84] 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, which they were later sued for. [85] [86]

    Subsequent research failed to confirm the utility of ivermectin for COVID-19, [87] [88] and in 2021 it emerged that many of the studies demonstrating benefit were faulty, misleading, or fraudulent. [89] [90] Nevertheless, misinformation about ivermectin continued to be propagated on social media and the drug remained a cause célèbre for anti-vaccinationists and conspiracy theorists. [91]

    Economics

    The initial price proposed by Merck in 1987 was US$ 6 per treatment, which was unaffordable for patients who most needed ivermectin. [92] The company donated hundreds of millions of courses of treatments since 1988 in more than 30 countries. [92] 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. [93]

    Ivermectin is considered an inexpensive drug. [94] 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). [95]

    As of 2019, the cost effectiveness of treating scabies and lice with ivermectin has not been studied. [96] [97]

    Brand names

    It is sold under the brand names Heartgard, Sklice [98] and Stromectol [3] in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT [99] 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. [100]

    Research

    Parasitic disease

    Ivermectin has been researched in laboratory animals, as a potential treatment for trichinosis [31] and trypanosomiasis. [101]

    Tropical diseases

    As of 2016 ivermectin was studied as a potential antiviral agent against chikungunya and yellow fever. [102] In chikungunya, ivermectin showed a wide in vitro safety margin as an antiviral. [102]

    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. [103] [104] A direct effect on malaria parasites could not be shown in an experimental infection of volunteers with Plasmodium falciparum . [105] 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. [106] [58] 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. [107] 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. [106]

    One alternative to ivermectin is moxidectin, which has been approved by the Food and Drug Administration for use in people with river blindness. [108] 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. [109] [110]

    There is tentative evidence that ivermectin kills bedbugs, as part of integrated pest management for bedbug infestations. [111] [112] [113] However, such use may require a prolonged course of treatment which is of unclear safety. [114]

    NAFLD

    In 2013, ivermectin was demonstrated as a novel ligand of the farnesoid X receptor, [115] [116] a therapeutic target for nonalcoholic fatty liver disease. [117]

    COVID-19

    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. [118] [119]

    Veterinary use

    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, this is because of an increase in anthelmintic resistance. [120] This resistance has arisen from the persistent use of the same anthelmintic drugs for the past 40 years. [121] [122] 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. [123]

    In dogs, ivermectin is routinely used as prophylaxis against heartworm. [124] 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. [125] 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. [126] [127] Clinical evidence suggests 7-week-old kittens are susceptible to ivermectin toxicity. [128] A 0.01% ivermectin topical preparation for treating ear mites in cats is available. [129]

    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. [130]

    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. [78]

    For dogs, the insecticide spinosad may have the effect of increasing the toxicity of ivermectin. [131] [132]

    Notes

    1. ↑ This recommendation is not universal. The World Health Organization recommends ascariasis be treated with mebendazole or pyrantel pamoate, [37] while the textbook Parasitic Diseases recommends albendazole or mebendazole. [38] A 2020 Cochrane review concluded that the three drugs are equally safe and effective for treating ascariasis. [39]
    1. ↑ New Drug Application Identifier: 50-742/S-022

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    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.

    <span class="mw-page-title-main">Moxidectin</span> Chemical compound

    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 and sheep. 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.

    <span class="mw-page-title-main">Hydroxychloroquine</span> Antimalarial medication

    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.

    <span class="mw-page-title-main">Avermectin</span> Drugs to treat parasitic worms and insect pests

    The avermectins are a series of drugs and pesticides used to treat parasitic worm infestations and to reduce insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. Eight different avermectins were isolated in four pairs of homologue compounds, with a major (a-component) and minor (b-component) component usually in ratios of 80:20 to 90:10. Avermectin B1, a mixture of B1a and B1b, is the drug and pesticide abamectin. Other anthelmintics derived from the avermectins include ivermectin, selamectin, doramectin, eprinomectin.

    <i>Mansonella perstans</i> Species of roundworm

    Mansonella perstans is a filarial (arthropod-borne) nematode (roundworm), transmitted by tiny blood-sucking flies called midges. Mansonella perstans is one of two filarial nematodes that causes serous cavity filariasis in humans. The other filarial nematode is Mansonella ozzardi. M. perstans is widespread in many parts of sub-Saharan Africa, parts of Central and South America, and the Caribbean.

    <span class="mw-page-title-main">Anthelmintic</span> Antiparasitic drugs that expel parasitic worms (helminths) from the body

    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.

    <span class="mw-page-title-main">William C. Campbell (scientist)</span> Nobel Winner, co-inventor of ivermectin

    William Cecil Campbell is an Irish biologist and parasitologist with United States citizenship, 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 is currently 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.

    <span class="mw-page-title-main">COVID-19 drug repurposing research</span> Drug repurposing research related to COVID-19

    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.

    <span class="mw-page-title-main">Chloroquine and hydroxychloroquine during the COVID-19 pandemic</span> Early experimental treatment efforts during the start of COVID-19 pandemic

    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 has been associated with increased mortality and adverse effects, such as QT prolongation. Researchers estimate that off-label use of hydroxychloroquine in hospitals during the first phase of the pandemic caused 17,000 deaths worldwide. The widespread administration of chloroquine or hydroxychloroquine, either as monotherapies or in conjunction with azithromycin, has been associated with deleterious outcomes, including QT interval 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.

    <span class="mw-page-title-main">Ivermectin during the COVID-19 pandemic</span> Uses of drug ivermectin during the COVID-19 pandemic

    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.

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