:Ivermectin

Ivermectin is used to treat human diseases caused by roundworms and a wide variety of external parasites.{{cite journal | vauthors = Crump A | title = Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations | journal = The Journal of Antibiotics | volume = 70 | issue = 5 | pages = 495–505 | date = May 2017 | pmid = 28196978 | doi = 10.1038/ja.2017.11 | doi-access = free }}

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.{{cite journal | vauthors = Ashour DS | title = Ivermectin: From theory to clinical application | journal = International Journal of Antimicrobial Agents | volume = 54 | issue = 2 | pages = 134–142 | date = August 2019 | pmid = 31071469 | doi = 10.1016/j.ijantimicag.2019.05.003 | s2cid = 149445017 }} 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{{ndash}}15-year lifespan of the adult worms.{{cite web |date=June 14, 2019 |title=Onchocerciasis |url=https://www.who.int/news-room/fact-sheets/detail/onchocerciasis |access-date=January 11, 2021 |publisher=World Health Organization |archive-date=April 11, 2020 |archive-url=https://web.archive.org/web/20200411123533/https://www.who.int/news-room/fact-sheets/detail/onchocerciasis |url-status=live}}

The World Health Organization (WHO) considers ivermectin the drug of choice for strongyloidiasis.{{cite web|title=Strongyloidiasis|url=https://www.who.int/intestinal_worms/epidemiology/strongyloidiasis/en/|access-date=January 25, 2021|publisher=World Health Organization|archive-date=October 19, 2021|archive-url=https://ghostarchive.org/archive/20211019/https://www.who.int/intestinal_worms/epidemiology/strongyloidiasis/en/|url-status=dead}} Ivermectin is also the primary treatment for Mansonella ozzardi and cutaneous larva migrans.{{cite book |url=https://parasiteswithoutborders.com/wp-content/uploads/2020/02/PD7thEditionLowResVersion5-11-2019.pdf |title=Parasitic Diseases |vauthors=Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA |date=2019 |publisher=Parasites Without Borders |edition=7 |location=New York|access-date=January 26, 2021 |archive-date=November 24, 2021 |archive-url=https://web.archive.org/web/20211124214329/https://parasiteswithoutborders.com/wp-content/uploads/2020/02/PD7thEditionLowResVersion5-11-2019.pdf |url-status=live}}{{rp|p=294}}{{rp|p=299}} The US Centers for Disease Control and Prevention (CDC) recommends ivermectin, albendazole, or mebendazole as treatments for ascariasis.{{cite web |date=May 20, 2020 |title=Ascariasis – Resources for Health Professionals |url=https://www.cdc.gov/parasites/ascariasis/health_professionals/index.html#tx| archive-url=https://web.archive.org/web/20101121144213/http://www.cdc.gov/parasites/ascariasis/health_professionals/index.html#tx| archive-date=November 21, 2010 |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=February 10, 2021 | url-status = live }}{{efn|group=note|This recommendation is not universal. The World Health Organization recommends ascariasis be treated with mebendazole or pyrantel pamoate,{{cite web|title=Water related diseases – Ascariasis|url=https://www.who.int/water_sanitation_health/diseases-risks/diseases/ascariasis/en/|publisher=World Health Organization|access-date=February 10, 2021|archive-date=October 19, 2021|archive-url=https://ghostarchive.org/archive/20211019/https://www.who.int/water_sanitation_health/diseases-risks/diseases/ascariasis/en/|url-status=dead}} while the textbook Parasitic Diseases recommends albendazole or mebendazole.{{rp|p=211}} A 2020 Cochrane review concluded that the three drugs are equally safe and effective for treating ascariasis.{{cite journal | vauthors = Conterno LO, Turchi MD, Corrêa I, Monteiro de Barros Almeida RA | title = Anthelmintic drugs for treating ascariasis | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 4 | pages = CD010599 | date = April 2020 | pmid = 32289194 | pmc = 7156140 | doi = 10.1002/14651858.CD010599.pub2 }}}} Ivermectin is sometimes added to albendazole or mebendazole for whipworm treatment, and is considered a second-line treatment for gnathostomiasis.{{rp|p=299}}{{rp|p=201}} When co-administered, ivermectin and albendazole act in synergy. Ivermectin targets the parasite's nervous and muscular systems, causing paralysis, while albendazole disrupts the parasite's metabolism and energy production. This dual approach immobilizes and kills the parasite and improves the treatment's effectiveness.

In January 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive scientific opinion for ivermectin/albendazole for the treatment of infections caused by several types of worm parasites including lymphatic filariasis, a neglected tropical disease.{{cite web | title=New combination of medicines to treat parasitic worm infections | website=European Medicines Agency (EMA) | date=January 31, 2025 | url=https://www.ema.europa.eu/en/news/new-combination-medicines-treat-parasitic-worm-infections | access-date=February 16, 2025}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Ivermectin/albendazole is indicated for use in people aged five years of age or older, for the treatment of soil-transmitted helminth infections, caused by different types of intestinal parasitic worms, which are spread through soil contaminated by human feces in areas with poor sanitation. Among the worms responsible for these diseases are hookworms (Ancylostoma duodenale, Necator americanus), roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura) and a roundworm called Strongyloides stercoralis. Ivermectin/albendazole is also indicated for the treatment of microfilaraemia (the presence of worm larvae in the blood) in people with lymphatic filariasis. Lymphatic filariasis is a neglected tropical disease commonly known as elephantiasis, which impairs the lymphatic system and can lead to the abnormal enlargement of body parts, causing pain, severe disability and social stigma. Ivermectin/albendazole is indicated for the treatment of cases of lymphatic filariasis caused by Wuchereria bancrofti, a parasite which is responsible for 90% of cases worldwide.

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|date=September 2024}} 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.{{cite journal | vauthors = Thomas C, Coates SJ, Engelman D, Chosidow O, Chang AY | title = Ectoparasites: Scabies | journal = Journal of the American Academy of Dermatology | volume = 82 | issue = 3 | pages = 533–548 | date = March 2020 | pmid = 31310840 | doi = 10.1016/j.jaad.2019.05.109 | s2cid = 242599732 }}{{cite web |date=October 2, 2019 |title=Scabies – Medications |url=https://www.cdc.gov/parasites/scabies/health_professionals/meds.html |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=February 11, 2021 |archive-date=April 30, 2015 |archive-url=https://web.archive.org/web/20150430075605/http://www.cdc.gov/parasites/scabies/health_professionals/meds.html |url-status=live}} 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.{{Cite book | vauthors = Craig E |title=The Itch: Scabies |publisher=Oxford University Press |year=2022 |isbn=978-0-19-284840-6 |edition=1st |location=United Kingdom |pages=146–152}}

For severe "crusted scabies", where the parasite burden is orders of magnitude higher than usual, the CDC recommends up to seven doses of ivermectin over the course of a month, along with a topical antiparasitic. 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.{{cite journal | vauthors = Gunning K, Kiraly B, Pippitt K | title = Lice and Scabies: Treatment Update | journal = American Family Physician | volume = 99 | issue = 10 | pages = 635–642 | date = May 2019 | pmid = 31083883 }}{{cite web |date=September 12, 2019 |title=Pubic "Crab" Lice – Treatment |url=https://www.cdc.gov/parasites/lice/pubic/treatment.html |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=February 11, 2021 |archive-date=November 12, 2020 |archive-url=https://web.archive.org/web/20201112013500/https://www.cdc.gov/parasites/lice/pubic/treatment.html |url-status=live}} Ivermectin is also used to treat rosacea and blepharitis, both of which can be caused or exacerbated by Demodex folliculorum mites.{{cite journal | vauthors = van Zuuren EJ | title = Rosacea | journal = The New England Journal of Medicine | volume = 377 | issue = 18 | pages = 1754–1764 | date = November 2017 | pmid = 29091565 | doi = 10.1056/NEJMcp1506630 }}{{cite journal | vauthors = Elston CA, Elston DM | title = Demodex mites | journal = Clinics in Dermatology | volume = 32 | issue = 6 | pages = 739–743 | date = 2014 | pmid = 25441466 | doi = 10.1016/j.clindermatol.2014.02.012 }}

The only absolute contraindication to the use of ivermectin is hypersensitivity to the active ingredient or any component of the formulation.{{cite web |title=Ivermectin (PIM 292) |url=https://inchem.org/documents/pims/pharm/ivermect.htm |website=inchem.org |publisher=InChem |access-date=April 3, 2022 |archive-date=April 26, 2022 |archive-url=https://web.archive.org/web/20220426173526/https://inchem.org/documents/pims/pharm/ivermect.htm |url-status=live}}{{cite web |title=Stromectol (ivermectin) dose, indications, adverse effects, interactions |url=https://www.pdr.net/drug-summary/Stromectol-ivermectin-391 |website=www.pdr.net |publisher=Prescribers' Digital Reference |access-date=April 3, 2022 |archive-date=April 25, 2022 |archive-url=https://web.archive.org/web/20220425003811/https://www.pdr.net/drug-summary/Stromectol-ivermectin-391 |url-status=live}} In children under the age of five or those who weigh less than {{convert|15|kg|abbr=off}},{{cite journal | vauthors = Dourmishev AL, Dourmishev LA, Schwartz RA | title = Ivermectin: pharmacology and application in dermatology | journal = International Journal of Dermatology | volume = 44 | issue = 12 | pages = 981–988 | date = December 2005 | pmid = 16409259 | doi = 10.1111/j.1365-4632.2004.02253.x }} there is limited data regarding the efficacy or safety of ivermectin, though the available data demonstrate few adverse effects.{{cite journal | vauthors = Wilkins AL, Steer AC, Cranswick N, Gwee A | title = Question 1: Is it safe to use ivermectin in children less than five years of age and weighing less than 15 kg? | journal = Archives of Disease in Childhood | volume = 103 | issue = 5 | pages = 514–519 | date = May 2018 | pmid = 29463522 | doi = 10.1136/archdischild-2017-314505 | s2cid = 3441595 }} 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.{{cite journal |title=Ivermectin – Drug Monographs – Pediatric Care Online |journal=American Academy of Pediatrics Drug Monographs |date=August 2021 |url=https://publications.aap.org/pediatriccare/drug-monograph/18/6030 |access-date=April 2, 2022 |archive-date=June 10, 2022 |archive-url=https://web.archive.org/web/20220610025941/https://publications.aap.org/pediatriccare/drug-monograph/18/6030?autologincheck=redirected |url-status=live}} The American Academy of Family Physicians also recommends against use in these patients, given a lack of sufficient data to prove drug safety.{{cite journal |vauthors=Fawcett RS |title=Ivermectin Use in Scabies |journal=American Family Physician |date=September 15, 2003 |volume=68 |issue=6 |pages=1089–1092 |pmid=14524395 |url=https://www.aafp.org/afp/2003/0915/p1089.html |access-date=April 2, 2022 |issn=0002-838X |archive-date=December 27, 2021 |archive-url=https://web.archive.org/web/20211227192205/https://www.aafp.org/afp/2003/0915/p1089.html |url-status=live}} Ivermectin is secreted in very low concentration in breast milk.{{cite journal | vauthors = Koh YP, Tian EA, Oon HH | title = New changes in pregnancy and lactation labelling: Review of dermatologic drugs | journal = International Journal of Women's Dermatology | volume = 5 | issue = 4 | pages = 216–226 | date = September 2019 | pmid = 31700976 | pmc = 6831768 | doi = 10.1016/j.ijwd.2019.05.002 }} It remains unclear if ivermectin is safe during pregnancy.{{cite journal | vauthors = Nicolas P, Maia MF, Bassat Q, Kobylinski KC, Monteiro W, Rabinovich NR, Menéndez C, Bardají A, Chaccour C | title = Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis | journal = The Lancet. Global Health | volume = 8 | issue = 1 | pages = e92–e100 | date = January 2020 | pmid = 31839144 | doi = 10.1016/S2214-109X(19)30453-X | pmc = 7613514 | doi-access = free | title-link = doi }}

Side effects, although uncommon, include fever, itching, and skin rash when taken by mouth;{{cite web |title=Ivermectin |url=https://www.drugs.com/monograph/ivermectin.html |archive-url=https://web.archive.org/web/20160103191914/http://www.drugs.com/monograph/ivermectin.html |archive-date=January 3, 2016 |access-date=January 16, 2016 |publisher=The American Society of Health-System Pharmacists | url-status = live }} and red eyes, dry skin, and burning skin when used topically for head lice.{{cite web |date=July 27, 2020 |title=Ivermectin (topical) |url=https://www.drugs.com/monograph/ivermectin-topical.html |access-date=January 16, 2021 |publisher=The American Society of Health-System Pharmacists |archive-date=March 18, 2023 |archive-url=https://web.archive.org/web/20230318085345/https://www.drugs.com/monograph/ivermectin-topical.html |url-status=live}} It is unclear if the drug is safe for use during pregnancy, but it is probably acceptable for use during breastfeeding.{{cite web |title=Ivermectin Levels and Effects while Breastfeeding |url=https://www.drugs.com/breastfeeding/ivermectin.html |archive-url=https://web.archive.org/web/20160101113118/http://www.drugs.com/breastfeeding/ivermectin.html |archive-date=January 1, 2016 |access-date=January 16, 2016 |website=Drugs.com | url-status = live }}

Ivermectin is considered relatively free of toxicity in standard doses (around 300 μg/kg).{{cite journal | vauthors = Navarro M, Camprubí D, Requena-Méndez A, Buonfrate D, Giorli G, Kamgno J, Gardon J, Boussinesq M, Muñoz J, Krolewiecki A | title = Safety of high-dose ivermectin: a systematic review and meta-analysis | journal = The Journal of Antimicrobial Chemotherapy | volume = 75 | issue = 4 | pages = 827–834 | date = April 2020 | pmid = 31960060 | doi = 10.1093/jac/dkz524 }}{{cite journal | vauthors = Martin RJ, Robertson AP, Choudhary S | title = Ivermectin: An Anthelmintic, an Insecticide, and Much More | journal = Trends in Parasitology | volume = 37 | issue = 1 | pages = 48–64 | date = January 2021 | pmid = 33189582 | pmc = 7853155 | doi = 10.1016/j.pt.2020.10.005 | doi-access = free }} Based on the data drug safety sheet for ivermectin,{{Efn|New Drug Application Identifier: 50-742/S-022}} 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.{{cite journal | vauthors = Pion SD, Tchatchueng-Mbougua JB, Chesnais CB, Kamgno J, Gardon J, Chippaux JP, Ranque S, Ernould JC, Garcia A, Boussinesq M | title = Effect of a Single Standard Dose (150–200 μg/kg) of Ivermectin on Loa loa Microfilaremia: Systematic Review and Meta-analysis | journal = Open Forum Infectious Diseases | volume = 6 | issue = 4 | pages = ofz019 | date = April 2019 | pmid = 30968052 | pmc = 6449757 | doi = 10.1093/ofid/ofz019 }} 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.

One concern is neurotoxicity after large overdoses, which in most mammalian species may manifest as central nervous system depression, ataxia, coma, and death,{{cite journal | vauthors = Campillo JT, Boussinesq M, Bertout S, Faillie JL, Chesnais CB | title = Serious adverse reactions associated with ivermectin: A systematic pharmacovigilance study in sub-Saharan Africa and in the rest of the World | journal = PLOS Neglected Tropical Diseases | volume = 15 | issue = 4 | pages = e0009354 | date = April 2021 | pmid = 33878105 | pmc = 8087035 | doi = 10.1371/journal.pntd.0009354 | quote = "Few hours after administration: nausea, vomiting, abdominal pain, salivation, tachycardia, hypotension, ataxia, pyramidal signs, binocular diplopia" | doi-access = free }} as might be expected from potentiation of inhibitory chloride channels.{{cite journal | vauthors = El-Saber Batiha G, Alqahtani A, Ilesanmi OB, Saati AA, El-Mleeh A, Hetta HF, Magdy Beshbishy A | title = Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects | journal = Pharmaceuticals | volume = 13 | issue = 8 | page = 196 | date = August 2020 | pmid = 32824399 | pmc = 7464486 | doi = 10.3390/ph13080196 | quote = "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" | doi-access = free | title-link = doi }}

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, benzodiazepines, and glucocorticoids such as dexamethasone.{{cite book | vauthors = Brunton LL, Lazo JS, Paker KL |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics. |date=2006 |publisher=McGraw-Hill |location=New York |isbn=978-0-07-142280-2 | oclc = 1037399847 |edition=11th | pages = 1084–87 }}

During a typical treatment course, ivermectin can cause minor aminotransferase elevations. In rare cases it can cause mild clinically apparent liver disease.{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK548921/ | chapter = Ivermectin |date=2012 | title = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |location=Bethesda, Maryland |pmid=31644227 |access-date=May 30, 2021 |archive-date=March 18, 2023 |archive-url=https://web.archive.org/web/20230318085433/https://www.ncbi.nlm.nih.gov/books/NBK548921/ |url-status=live}}

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,{{cite journal | vauthors = Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A | title = The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug | journal = American Journal of Cancer Research | volume = 8 | issue = 2 | pages = 317–331 | date = 2018 | pmid = 29511601 | pmc = 5835698 }} 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). 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),{{cite journal | vauthors = Schmith VD, Zhou JJ, Lohmer LR | title = The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19 | journal = Clinical Pharmacology and Therapeutics | volume = 108 | issue = 4 | pages = 762–765 | date = October 2020 | pmid = 32378737 | pmc = 7267287 | doi = 10.1002/cpt.1889 }} high enough to be considered ivermectin poisoning. 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.{{Cite web|date=August 26, 2021|title=Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19|url=https://emergency.cdc.gov/han/2021/han00449.asp|access-date=September 4, 2021|website=Centers for Disease Control and Prevention|archive-date=March 18, 2023|archive-url=https://web.archive.org/web/20230318091159/https://emergency.cdc.gov/han/2021/han00449.asp | url-status = live }}

File:Ivermectin mechanism of action 3RHW.png 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 and its related drugs act by interfering with the nerve and muscle functions of helminths and insects. The drug binds to glutamate-gated chloride channels common to invertebrate nerve and muscle cells.{{cite journal | vauthors = Omura S, Crump A | title = Ivermectin: panacea for resource-poor communities? | journal = Trends in Parasitology | volume = 30 | issue = 9 | pages = 445–455 | date = September 2014 | pmid = 25130507 | doi = 10.1016/j.pt.2014.07.005 | doi-access = free }} The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, paralyzing and killing the invertebrate. 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.

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.{{cite journal | vauthors = González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ | title = The pharmacokinetics and interactions of ivermectin in humans—a mini-review | journal = The AAPS Journal | volume = 10 | issue = 1 | pages = 42–46 | date = 2008 | pmid = 18446504 | pmc = 2751445 | doi = 10.1208/s12248-007-9000-9 }}

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).{{cite journal | vauthors = Borst P, Schinkel AH | title = What have we learnt thus far from mice with disrupted P-glycoprotein genes? | journal = European Journal of Cancer | volume = 32A | issue = 6 | pages = 985–990 | date = June 1996 | pmid = 8763339 | doi = 10.1016/0959-8049(96)00063-9 }} 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.{{cite journal | vauthors = Teare JA, Bush M | title = Toxicity and efficacy of ivermectin in chelonians | journal = Journal of the American Veterinary Medical Association | volume = 183 | issue = 11 | pages = 1195–1197 | date = December 1983 | doi = 10.2460/javma.1983.183.11.1195 | pmid = 6689009 | url = https://repository.si.edu/bitstream/handle/10088/4426/Teare1983.pdf | access-date = October 26, 2021 | archive-url = https://web.archive.org/web/20211025214737/https://repository.si.edu/bitstream/handle/10088/4426/Teare1983.pdf | archive-date = October 25, 2021 | url-status = live }}

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.{{cite journal | vauthors = Kern C, Müller P, Chaccour C, Liechti ME, Hammann F, Duthaler U | title = Pharmacokinetics of ivermectin metabolites and their activity against Anopheles stephensi mosquitoes | journal = Malaria Journal | volume = 22 | issue = 1 | pages = 194 | date = June 2023 | pmid = 37355605 | pmc = 10290335 | doi = 10.1186/s12936-023-04624-0 | doi-access = free }}

File:Avermectins.png

Fermentation of Streptomyces avermitilis yields eight closely related avermectin homologues, of which B_1a and B_1b 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.{{cite journal | vauthors = Lasota JA, Dybas RA | title = Avermectins, a novel class of compounds: implications for use in arthropod pest control | journal = Annual Review of Entomology | volume = 36 | pages = 91–117 | year = 1991 | pmid = 2006872 | doi = 10.1146/annurev.en.36.010191.000515 }}{{cite book |title=Insecticides with Novel Modes of Action |vauthors=Jansson RK, Dybas RA |publisher=Springer |year=1998 |isbn=978-3-642-08314-3 |series=Applied Agriculture |location=Berlin, Heidelberg |pages=152–70 |chapter=Avermectins: Biochemical Mode of Action, Biological Activity and Agricultural Importance |doi=10.1007/978-3-662-03565-8_9}}

Ivermectin is a macrocyclical lactone.{{cite journal | vauthors = Campbell WC | title = Ivermectin: an update | journal = Parasitology Today | volume = 1 | issue = 1 | pages = 10–16 | date = July 1985 | pmid = 15275618 | doi = 10.1016/0169-4758(85)90100-0 }}

The avermectin family of compounds was discovered by Satoshi Ōmura of Kitasato University and William Campbell of Merck. In 1970, Ōmura isolated a strain of Streptomyces avermitilis from woodland soil near a golf course along the southeast coast of Honshu, Japan.{{cite journal | vauthors = Laing R, Gillan V, Devaney E | title = Ivermectin – Old Drug, New Tricks? | journal = Trends in Parasitology | volume = 33 | issue = 6 | pages = 463–472 | date = June 2017 | pmid = 28285851 | pmc = 5446326 | doi = 10.1016/j.pt.2017.02.004 }} Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm Heligmosomoides polygyrus. 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'). Of the various avermectins, Campbell's group found the compound "avermectin B₁" to be the most potent when taken orally. They synthesized modified forms of avermectin B₁ to improve its pharmaceutical properties, eventually choosing a mixture of at least 80% 22,23-dihydroavermectin B_1a and up to 20% 22,23-dihydroavermectin B_1b, a combination they called "ivermectin".{{cite journal | vauthors = Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA | title = Ivermectin: a potent new antiparasitic agent | journal = Science | volume = 221 | issue = 4613 | pages = 823–828 | date = August 1983 | pmid = 6308762 | doi = 10.1126/science.6308762 | bibcode = 1983Sci...221..823C }}

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."{{cite journal | vauthors = Campbell WC | title = Serendipity and new drugs for infectious disease | journal = ILAR Journal | volume = 46 | issue = 4 | pages = 352–356 | date = January 1, 2005 | pmid = 16179743 | doi = 10.1093/ilar.46.4.352 | doi-access = free | title-link = doi }}

Merck began marketing ivermectin as a veterinary antiparasitic in 1981. By 1986, ivermectin was registered for use in 46 countries and was administered massively to cattle, sheep, and other animals.{{cite journal | vauthors = Omura S, Crump A | title = The life and times of ivermectin – a success story | journal = Nature Reviews. Microbiology | volume = 2 | issue = 12 | pages = 984–989 | date = December 2004 | pmid = 15550944 | doi = 10.1038/nrmicro1048 | s2cid = 22722403 }} By the late 1980s, ivermectin was the bestselling veterinary medicine in the world. 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.{{cite journal | vauthors = Molyneux DH, Ward SA | title = Reflections on the Nobel Prize for Medicine 2015—The Public Health Legacy and Impact of Avermectin and Artemisinin | journal = Trends in Parasitology | volume = 31 | issue = 12 | pages = 605–607 | date = December 2015 | pmid = 26552892 | doi = 10.1016/j.pt.2015.10.008 }} They found it to be highly safe and effective,{{cite journal | vauthors = Crump A, Morel CM, Omura S | title = The onchocerciasis chronicle: from the beginning to the end? | journal = Trends in Parasitology | volume = 28 | issue = 7 | pages = 280–288 | date = July 2012 | pmid = 22633470 | doi = 10.1016/j.pt.2012.04.005 | doi-access = free | title-link = doi }} triggering Merck to register ivermectin for human use as "Mectizan" in France in 1987. A year later, Merck CEO Roy Vagelos agreed that Merck would donate all ivermectin needed to eradicate river blindness. In 1998, that donation would be expanded to include ivermectin used to treat lymphatic filariasis.

Ivermectin earned the title of "wonder drug" for the treatment of nematodes and arthropod parasites.{{cite journal | vauthors = Geary TG | title = Ivermectin 20 years on: maturation of a wonder drug | journal = Trends in Parasitology | volume = 21 | issue = 11 | pages = 530–532 | date = November 2005 | pmid = 16126457 | doi = 10.1016/j.pt.2005.08.014 }} Ivermectin has been used safely by hundreds of millions of people to treat river blindness and lymphatic filariasis.

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".{{cite web |title=The Nobel Prize in Physiology or Medicine 2015 |url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.pdf |archive-url=https://web.archive.org/web/20151006112430/http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.pdf |archive-date=October 6, 2015 |access-date=October 7, 2015 |publisher=Nobel Foundation | url-status = dead }}{{cite web | title=The Nobel Prize in Physiology or Medicine 2015 | website=NobelPrize.org | date=March 18, 2023 | url=https://www.nobelprize.org/prizes/medicine/2015/summary/ | access-date=March 18, 2023 | archive-date=May 23, 2020 | archive-url=https://web.archive.org/web/20200523072744/https://www.nobelprize.org/prizes/medicine/2015/summary/ | url-status = live }}

{{Excerpt |Ivermectin during the COVID-19 pandemic |paragraphs=2–3 |only=paragraphs}}

The initial price proposed by Merck in 1987 was {{Currency|6|USD}} per treatment, which was unaffordable for patients who most needed ivermectin.{{cite journal | vauthors = Crump A, Ōmura S | title = Ivermectin, 'wonder drug' from Japan: the human use perspective | journal = Proceedings of the Japan Academy. Series B, Physical and Biological Sciences | volume = 87 | issue = 2 | pages = 13–28 | date = 2011 | pmid = 21321478 | pmc = 3043740 | doi = 10.2183/pjab.87.13 | bibcode = 2011PJAB...87...13C }} The company donated hundreds of millions of courses of treatments since 1988 in more than 30 countries. 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 {{Currency|257 million|USD|passthrough=yes}}.{{cite book |url=https://books.google.com/books?id=e0nYBAAAQBAJ&pg=PT158 |title=African Health Leaders: Making Change and Claiming the Future |vauthors=Omaswa F, Crisp N |date=2014 |publisher=OUP Oxford |isbn=978-0191008412 |page=PT158 |access-date=April 6, 2020 |archive-date=August 3, 2020 |archive-url=https://web.archive.org/web/20200803122732/https://books.google.com/books?id=e0nYBAAAQBAJ&pg=PT158 |url-status=live}}

Ivermectin is considered an inexpensive drug.{{cite journal | vauthors = Arévalo AP, Pagotto R, Pórfido JL, Daghero H, Segovia M, Yamasaki K, Varela B, Hill M, Verdes JM, Duhalde Vega M, Bollati-Fogolín M, Crispo M | title = Ivermectin reduces in vivo coronavirus infection in a mouse experimental model | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 7132 | date = March 2021 | pmid = 33785846 | pmc = 8010049 | doi = 10.1038/s41598-021-86679-0 | bibcode = 2021NatSR..11.7132A }} As of 2019, ivermectin tablets (Stromectol) in the United States were the least expensive treatment option for lice in children at approximately {{Currency|9.30|USD|passthrough=yes}}, while Sklice, an ivermectin lotion, cost around {{Currency|300|USD}} for {{Convert|4|USfloz|mL|order=flip|abbr=on|sigfig=2}}.{{cite book|url=https://books.google.com/books?id=LJuRDwAAQBAJ&pg=PA3867|title=Nelson Textbook of Pediatrics E-Book|vauthors=Kliegman RM, St Geme J|date=2019|publisher=Elsevier Health Sciences|isbn=978-0323568883|page=3575|access-date=April 6, 2020|archive-date=August 3, 2020|archive-url=https://web.archive.org/web/20200803115812/https://books.google.com/books?id=LJuRDwAAQBAJ&pg=PA3867|url-status=live}}

{{As of|2019|}}, the cost effectiveness of treating scabies and lice with ivermectin has not been studied.{{cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK545083/|title=Ivermectin for Parasitic Skin Infections of Scabies: A Review of Comparative Clinical Effectiveness, Cost-Effectiveness, and Guidelines|vauthors=Chiu S, Argaez C|date=2019|publisher=Canadian Agency for Drugs and Technologies in Health|series=CADTH Rapid Response Reports|location=Ottawa (ON)|pmid=31424718|access-date=July 4, 2020|archive-date=March 18, 2023|archive-url=https://web.archive.org/web/20230318091248/https://www.ncbi.nlm.nih.gov/books/NBK545083/|url-status=live}}{{cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK545892/|title=Ivermectin for Parasitic Skin Infections of Lice: A Review of Comparative Clinical Effectiveness, Cost-Effectiveness, and Guidelines|vauthors=Young C, Argáez C|date=2019|publisher=Canadian Agency for Drugs and Technologies in Health|series=CADTH Rapid Response Reports|location=Ottawa (ON)|pmid=31487135|access-date=July 4, 2020|archive-date=October 19, 2021|archive-url=https://ghostarchive.org/archive/20211019/http://www.ncbi.nlm.nih.gov/books/NBK545892/|url-status=live}}

It is sold under the brand names Heartgard, Sklice,{{cite web |date=November 9, 2017 |title=Sklice – ivermectin lotion |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c74905e6-fc04-4244-880b-98ab0551df21 |access-date=October 28, 2020 |website=DailyMed |archive-date=October 31, 2020 |archive-url=https://web.archive.org/web/20201031131544/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c74905e6-fc04-4244-880b-98ab0551df21 |url-status=live}} and Stromectol{{cite web |date=December 15, 2019 |title=Stromectol – ivermectin tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=681888c9-af79-4b7d-ae80-c3f4f6f1effd |access-date=October 28, 2020 |website=DailyMed |archive-date=October 31, 2020 |archive-url=https://web.archive.org/web/20201031133921/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=681888c9-af79-4b7d-ae80-c3f4f6f1effd |url-status=live}} in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT{{cite web |date=May 27, 2014 |title=Alive Pharmaceutical (P) LTD.: Iver-DT |url=http://alivepharmaceutical.blogspot.com/2014/05/iver-dt.html |archive-url=https://web.archive.org/web/20160304223410/http://alivepharmaceutical.blogspot.com/2014/05/iver-dt.html |archive-date=March 4, 2016 |access-date=October 7, 2015 |website=Alive Pharmaceutical (P) LTD. |vauthors=Adhikari S | url-status = dead }} 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.{{cite web |title=Soolantra – ivermectin cream |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1d5b166-ab06-4ab5-b0c6-31126238118a |access-date=July 18, 2021 |website=DailyMed |archive-date=July 19, 2021 |archive-url=https://web.archive.org/web/20210719061814/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1d5b166-ab06-4ab5-b0c6-31126238118a |url-status=live}} While in development, it was assigned the code MK-933 by Merck.{{cite journal | vauthors = Pampiglione S, Majori G, Petrangeli G, Romi R | title = Avermectins, MK-933 and MK-936, for mosquito control | journal = Transactions of the Royal Society of Tropical Medicine and Hygiene | volume = 79 | issue = 6 | pages = 797–799 | year = 1985 | pmid = 3832491 | doi = 10.1016/0035-9203(85)90121-X }}

Ivermectin has been researched in laboratory animals, as a potential treatment for trichinosis and trypanosomiasis.{{ cite journal | vauthors = Udensi K | title = Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected mice | journal = Journal of Vector Borne Diseases| date = September 2012 | volume = 49 | issue = 3 | pages = 143–150 | doi = 10.4103/0972-9062.213454 | doi-access = free | pmid = 23135008 }}

Ivermectin has also been tested on zebrafish infected with Pseudocapillaria tomentosa.{{cite journal | vauthors = Kent ML, Watral V, Gaulke CA, Sharpton TJ | title = Further evaluation of the efficacy of emamectin benzoate for treating Pseudocapillaria tomentosa (Dujardin 1843) in zebrafish Danio rerio (Hamilton 1822) | journal = Journal of Fish Diseases | volume = 42 | issue = 10 | pages = 1351–1357 | date = October 2019 | pmid = 31309582 | pmc = 6744302 | doi = 10.1111/jfd.13057 | bibcode = 2019JFDis..42.1351K }}

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.{{cite journal | vauthors = Chaccour C, Hammann F, Rabinovich NR | title = Ivermectin to reduce malaria transmission I. Pharmacokinetic and pharmacodynamic considerations regarding efficacy and safety | journal = Malaria Journal | volume = 16 | issue = 1 | pages = 161 | date = April 2017 | pmid = 28434401 | pmc = 5402169 | doi = 10.1186/s12936-017-1801-4 | doi-access = free }}{{cite journal | vauthors = Siewe Fodjo JN, Kugler M, Hotterbeekx A, Hendy A, Van Geertruyden JP, Colebunders R | title = Would ivermectin for malaria control be beneficial in onchocerciasis-endemic regions? | journal = Infectious Diseases of Poverty | volume = 8 | issue = 1 | pages = 77 | date = August 2019 | pmid = 31439040 | pmc = 6706915 | doi = 10.1186/s40249-019-0588-7 | doi-access = free }} A direct effect on malaria parasites could not be shown in an experimental infection of volunteers with Plasmodium falciparum.{{cite journal | vauthors = Fontinha D, Moules I, Prudêncio M | title = Repurposing Drugs to Fight Hepatic Malaria Parasites | journal = Molecules | volume = 25 | issue = 15 | pages = 3409 | date = July 2020 | pmid = 32731386 | pmc = 7435416 | doi = 10.3390/molecules25153409 | doi-access = free | title-link = doi }} 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.{{cite journal | vauthors = de Souza DK, Thomas R, Bradley J, Leyrat C, Boakye DA, Okebe J | title = Ivermectin treatment in humans for reducing malaria transmission | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 6 | pages = CD013117 | date = June 2021 | pmid = 34184757 | pmc = 8240090 | doi = 10.1002/14651858.CD013117.pub2 | collaboration = Cochrane Infectious Diseases Group }} 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.{{cite journal | vauthors = Tizifa TA, Kabaghe AN, McCann RS, van den Berg H, Van Vugt M, Phiri KS | title = Prevention Efforts for Malaria | journal = Current Tropical Medicine Reports | volume = 5 | issue = 1 | pages = 41–50 | date = 2018 | pmid = 29629252 | pmc = 5879044 | doi = 10.1007/s40475-018-0133-y }} 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.

One alternative to ivermectin is moxidectin, which has been approved by the Food and Drug Administration for use in people with river blindness.{{cite journal | vauthors = Milton P, Hamley JI, Walker M, Basáñez MG | title = Moxidectin: an oral treatment for human onchocerciasis | journal = Expert Review of Anti-Infective Therapy | volume = 18 | issue = 11 | pages = 1067–1081 | date = November 2020 | pmid = 32715787 | doi = 10.1080/14787210.2020.1792772 | doi-access = free | hdl = 10044/1/81294 | hdl-access = free }} 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.{{cite journal | vauthors = Maheu-Giroux M, Joseph SA | title = Moxidectin for deworming: from trials to implementation | journal = The Lancet. Infectious Diseases | volume = 18 | issue = 8 | pages = 817–819 | date = August 2018 | pmid = 29858152 | doi = 10.1016/S1473-3099(18)30270-6 | s2cid = 46921091 }}{{cite journal | vauthors = Boussinesq M | title = A new powerful drug to combat river blindness | journal = Lancet | volume = 392 | issue = 10154 | pages = 1170–1172 | date = October 2018 | pmid = 29361336 | doi = 10.1016/S0140-6736(18)30101-6 | doi-access = free | title-link = doi }} {{open access}}

There is tentative evidence that ivermectin kills bedbugs, as part of integrated pest management for bedbug infestations.{{cite journal | vauthors = Ōmura S | title = A Splendid Gift from the Earth: The Origins and Impact of the Avermectins (Nobel Lecture) | journal = Angewandte Chemie | volume = 55 | issue = 35 | pages = 10190–10209 | date = August 2016 | pmid = 27435664 | doi = 10.1002/anie.201602164 | url = https://www.nobelprize.org/prizes/medicine/2015/omura/lecture/ | access-date = April 6, 2020 | archive-date = October 19, 2021 | archive-url = https://ghostarchive.org/archive/20211019/https://www.nobelprize.org/prizes/medicine/2015/omura/lecture/ | url-status = live }}{{cite book |url=https://books.google.com/books?id=Np6cCQAAQBAJ&pg=PA439 |title=Andrews' Diseases of the Skin: Clinical Dermatology |vauthors=James WD, Elston D, Berger T, Neuhaus I |date=2015 |publisher=Elsevier Health Sciences |isbn=978-0323319690 |page=439 |quote=Ivermectin treatment is emerging as a potential ancillary measure. |access-date=April 6, 2020 |archive-date=June 26, 2020 |archive-url=https://web.archive.org/web/20200626152437/https://books.google.com/books?id=Np6cCQAAQBAJ&pg=PA439 |url-status=live}} However, such use may require a prolonged course of treatment which is of unclear safety.{{cite book |url=https://books.google.com/books?id=KuM2DwAAQBAJ&pg=PA89 |title=Treatment of Skin Disease: Comprehensive Therapeutic Strategies |vauthors=Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I |date=2017 |publisher=Elsevier Health Sciences |isbn=978-0702069130 |page=89 |access-date=April 6, 2020 |archive-date=June 26, 2020 |archive-url=https://web.archive.org/web/20200626152436/https://books.google.com/books?id=KuM2DwAAQBAJ&pg=PA89 |url-status=live}}

In 2013, ivermectin was demonstrated as a novel ligand of the farnesoid X receptor,{{cite journal | vauthors = Carotti A, Marinozzi M, Custodi C, Cerra B, Pellicciari R, Gioiello A, Macchiarulo A | title = Beyond bile acids: targeting Farnesoid X Receptor (FXR) with natural and synthetic ligands | journal = Current Topics in Medicinal Chemistry | volume = 14 | issue = 19 | pages = 2129–2142 | year = 2014 | pmid = 25388537 | doi = 10.2174/1568026614666141112094058 | url = https://www.researchgate.net/publication/268231666 | access-date = April 6, 2020 | archive-date = October 19, 2021 | archive-url = https://ghostarchive.org/archive/20211019/https://www.researchgate.net/publication/268231666 | url-status = live }}{{cite journal | vauthors = Jin L, Feng X, Rong H, Pan Z, Inaba Y, Qiu L, Zheng W, Lin S, Wang R, Wang Z, Wang S, Liu H, Li S, Xie W, Li Y | title = The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism | journal = Nature Communications | volume = 4 | pages = 1937 | date = 2013 | pmid = 23728580 | doi = 10.1038/ncomms2924 | bibcode = 2013NatCo...4.1937J | doi-access = free | title-link = doi }} a therapeutic target for nonalcoholic fatty liver disease (NAFLD).{{cite journal | vauthors = Kim SG, Kim BK, Kim K, Fang S | title = Bile Acid Nuclear Receptor Farnesoid X Receptor: Therapeutic Target for Nonalcoholic Fatty Liver Disease | journal = Endocrinology and Metabolism | volume = 31 | issue = 4 | pages = 500–504 | date = December 2016 | pmid = 28029021 | pmc = 5195824 | doi = 10.3803/EnM.2016.31.4.500 }}

{{see|Ivermectin during the COVID-19 pandemic#Research}}

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.{{cite journal | vauthors = Reis G, Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, Dos Santos CV, Campos VH, Nogueira AM, de Almeida AP, Callegari ED, Neto AD, Savassi LC, Simplicio MI, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Rowland-Yeo K, Guyatt GH, Boulware DR, Rayner CR, Mills EJ | title = Effect of Early Treatment with Ivermectin among Patients with Covid-19 | journal = The New England Journal of Medicine | volume = 386 | issue = 18 | pages = 1721–1731 | date = May 2022 | pmid = 35353979 | pmc = 9006771 | doi = 10.1056/NEJMoa2115869 }}

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.{{cite journal | vauthors = Kaplan RM, Vidyashankar AN | title = An inconvenient truth: global worming and anthelmintic resistance | journal = Veterinary Parasitology | volume = 186 | issue = 1–2 | pages = 70–78 | date = May 2012 | pmid = 22154968 | doi = 10.1016/j.vetpar.2011.11.048 }} This resistance has arisen from the persistent use of the same anthelmintic drugs for the past 40 years.{{cite journal | vauthors = Geurden T, Chartier C, Fanke J, di Regalbono AF, Traversa D, von Samson-Himmelstjerna G, Demeler J, Vanimisetti HB, Bartram DJ, Denwood MJ | title = Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe | journal = International Journal for Parasitology: Drugs and Drug Resistance | volume = 5 | issue = 3 | pages = 163–171 | date = December 2015 | pmid = 26448902 | pmc = 4572401 | doi = 10.1016/j.ijpddr.2015.08.001 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Peña-Espinoza M, Thamsborg SM, Denwood MJ, Drag M, Hansen TV, Jensen VF, Enemark HL | title = Efficacy of ivermectin against gastrointestinal nematodes of cattle in Denmark evaluated by different methods for analysis of faecal egg count reduction | journal = International Journal for Parasitology: Drugs and Drug Resistance | volume = 6 | issue = 3 | pages = 241–250 | date = December 2016 | pmid = 27835769 | pmc = 5107639 | doi = 10.1016/j.ijpddr.2016.10.004 | doi-access = free | title-link = doi }} 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.{{cite journal | vauthors = Verdú JR, Cortez V, Ortiz AJ, Lumaret JP, Lobo JM, Sánchez-Piñero F | title = Biomagnification and body distribution of ivermectin in dung beetles | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 9073 | date = June 2020 | pmid = 32493927 | doi = 10.1038/s41598-020-66063-0 | pmc = 7270108 | bibcode = 2020NatSR..10.9073V | hdl = 10481/63204 | hdl-access = free }}

In dogs, ivermectin is routinely used as prophylaxis against heartworm.{{cite book |vauthors=Papich MG |date=January 1, 2016 | title = Saunders Handbook of Veterinary Drugs | edition = Fourth |publisher=W.B. Saunders |isbn=978-0-323-24485-5 |veditors=Papich MG |pages=420–23 |chapter=Ivermectin |doi=10.1016/B978-0-323-24485-5.00323-5 }} 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.{{cite journal | vauthors = Dowling P | title = Pharmacogenetics: it's not just about ivermectin in collies | journal = The Canadian Veterinary Journal | volume = 47 | issue = 12 | pages = 1165–1168 | date = December 2006 | pmid = 17217086 | pmc = 1636591 }} 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.{{cite web |title=MDR1 FAQs |url=http://www.ashgi.org/articles/mdr1.htm |archive-url=https://web.archive.org/web/20071213125320/http://www.ashgi.org/articles/mdr1.htm |archive-date=December 13, 2007 |publisher=Australian Shepherd Health & Genetics Institute, Inc. | url-status = live }}{{cite web |title=Multidrug Sensitivity in Dogs |url=http://vcpl.vetmed.wsu.edu/vcpl-home |archive-url=https://web.archive.org/web/20150623212433/http://vcpl.vetmed.wsu.edu/vcpl-home |archive-date=June 23, 2015 |publisher=Washington State University's College of Veterinary Medicine | url-status = live }} For dogs, the insecticide spinosad may have the effect of increasing the toxicity of ivermectin.{{cite web |title=Comfortis- spinosad tablet, chewable |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9e5580d1-d8ea-4e8d-9156-1741b13ba8c9 |access-date=August 14, 2021 |website=DailyMed |archive-date=August 15, 2021 |archive-url=https://web.archive.org/web/20210815053323/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9e5580d1-d8ea-4e8d-9156-1741b13ba8c9 |url-status=live}}{{cite web |title=Comfortis and ivermectin interaction Safety Warning Notification |url=https://www.fda.gov/animalveterinary/newsevents/cvmupdates/ucm047942.htm |archive-url=https://web.archive.org/web/20090829064135/https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm047942.htm |archive-date=August 29, 2009 |publisher=U.S. Food and Drug Administration (FDA) | url-status = dead }}

A 0.01% ivermectin topical preparation for treating ear mites in cats is available.{{cite web |date=April 11, 2016 |title=Acarexx |url=https://www.bi-vetmedica.com/species/pet/products/acarexx.html |publisher=Boehringer Ingelheim |access-date=February 16, 2019 |archive-date=October 19, 2021 |archive-url=https://ghostarchive.org/archive/20211019/https://www.bi-vetmedica.com/species/pet/products/acarexx.html |url-status=live}} Clinical evidence suggests 7-week-old kittens are susceptible to ivermectin toxicity.{{cite journal | vauthors = Frischke H, Hunt L | title = Alberta. Suspected ivermectin toxicity in kittens | journal = The Canadian Veterinary Journal | volume = 32 | issue = 4 | pages = 245 | date = April 1991 | pmid = 17423775 | pmc = 1481314 }}

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.{{cite book |title=Understanding reptile parasites: from the experts at Advanced Vivarium Systems |vauthors=Klingenberg R |publisher=Advanced Vivarium Systems |year=2007 |isbn=978-1882770908 |location=Irvine, Calif}}

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.

{{reflist|group=note}}

{{notelist}}

{{Reflist}}

{{commons category}}

• {{cite web |title=Ivermectin Topical |url=https://medlineplus.gov/druginfo/meds/a613011.html| website=MedlinePlus}}

{{Other dermatological preparations}}

{{Anthelmintics}}

{{Ectoparasiticides}}

{{Navboxes

| title = Pharmacodynamics

| titlestyle = background:#ccccff

| list1 =

{{FXR and LXR modulators}}

{{GABAA receptor positive modulators}}

{{Glycine receptor modulators}}

{{Nicotinic acetylcholine receptor modulators}}

{{Purine receptor modulators}}

}}

{{Portal bar|Medicine}}

{{Authority control}}

Category:Acaricides

Category:Antiparasitic agents

Category:GABAA receptor positive allosteric modulators

Category:Glycine receptor agonists

Category:Insecticides

Category:Japanese inventions

Category:Macrolides

Category:Drugs developed by Merck & Co.

Category:Nicotinic agonists

Category:Peripherally selective drugs

Category:Veterinary drugs

Category:World Health Organization essential medicines

Category:Chloride channel openers

Category:Wikipedia medicine articles ready to translate