Jump to content

Ivermectin: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Restored revision 1023063928 by DMacks (talk): Let the software do the work; forcing width mucks up the appearance
→COVID-19 misinformation: Reword and cite EMA per talk.
Line 96: Line 96:
Ivermectin was discovered in 1975 and came into medical use in 1981.<ref name="Meh2008">{{cite book | vauthors = Mehlhorn H | title= Encyclopedia of parasitology |date=2008 |publisher=Springer |location=Berlin |isbn=978-3-540-48994-8 |page=646 |edition=3rd |url=https://books.google.com/books?id=Jpg1ysgVn-AC&pg=PA646 |url-status=live |archive-url=https://web.archive.org/web/20200626152441/https://books.google.com/books?id=Jpg1ysgVn-AC&pg=PA646 |archive-date=June 26, 2020 |df=mdy-all}}</ref><ref>{{cite book| veditors = Vercruysse J, Rew RS |title=Macrocyclic lactones in antiparasitic therapy|date=2002|publisher=CABI Pub.|location=Oxon, UK|isbn=978-0-85199-840-4|page=Preface|url=https://books.google.com/books?id=QXafQ91O74wC&pg=PR13|url-status=live|archive-url=https://web.archive.org/web/20160131121128/https://books.google.com/books?id=QXafQ91O74wC&pg=PR13|archive-date=January 31, 2016|df=mdy-all}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Ivermectin is [[FDA]]-approved as an [[antiparasitic agent]].<ref name="ahmed20">{{cite journal | vauthors = Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, Phru CS, Rahman M, Zaman K, Somani J, Yasmin R, Hasnat MA, Kabir A, Aziz AB, Khan WA | display-authors = 6 | title = A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness | journal = International Journal of Infectious Diseases | volume = 103 | pages = 214–216 | date = December 2020 | pmid = 33278625 | pmc = 7709596 | doi = 10.1016/j.ijid.2020.11.191 }}</ref>
Ivermectin was discovered in 1975 and came into medical use in 1981.<ref name="Meh2008">{{cite book | vauthors = Mehlhorn H | title= Encyclopedia of parasitology |date=2008 |publisher=Springer |location=Berlin |isbn=978-3-540-48994-8 |page=646 |edition=3rd |url=https://books.google.com/books?id=Jpg1ysgVn-AC&pg=PA646 |url-status=live |archive-url=https://web.archive.org/web/20200626152441/https://books.google.com/books?id=Jpg1ysgVn-AC&pg=PA646 |archive-date=June 26, 2020 |df=mdy-all}}</ref><ref>{{cite book| veditors = Vercruysse J, Rew RS |title=Macrocyclic lactones in antiparasitic therapy|date=2002|publisher=CABI Pub.|location=Oxon, UK|isbn=978-0-85199-840-4|page=Preface|url=https://books.google.com/books?id=QXafQ91O74wC&pg=PR13|url-status=live|archive-url=https://web.archive.org/web/20160131121128/https://books.google.com/books?id=QXafQ91O74wC&pg=PR13|archive-date=January 31, 2016|df=mdy-all}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Ivermectin is [[FDA]]-approved as an [[antiparasitic agent]].<ref name="ahmed20">{{cite journal | vauthors = Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, Phru CS, Rahman M, Zaman K, Somani J, Yasmin R, Hasnat MA, Kabir A, Aziz AB, Khan WA | display-authors = 6 | title = A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness | journal = International Journal of Infectious Diseases | volume = 103 | pages = 214–216 | date = December 2020 | pmid = 33278625 | pmc = 7709596 | doi = 10.1016/j.ijid.2020.11.191 }}</ref>


During the [[2020 COVID-19 pandemic]] misinformation was widely spread claiming that ivermectin was beneficial for treating and preventing COVID-19. Such claims are not backed by sound evidence.
During the [[2020 COVID-19 pandemic]] misinformation was widely spread claiming that ivermectin was beneficial for treating and preventing COVID-19. As of 2021 no reliable evidence exist to back up such claims.<ref>{{Cite web|date=March 22, 2021|title=EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials|url=https://www.ema.europa.eu/en/news/ema-advises-against-use-ivermectin-prevention-treatment-covid-19-outside-randomised-clinical-trials|url-status=live|publisher=[[European Medicines Agency]]}}</ref>


== Medical uses ==
== Medical uses ==
Line 162: Line 162:
===COVID-19 misinformation===
===COVID-19 misinformation===
{{further|COVID-19 misinformation#Ivermectin}}
{{further|COVID-19 misinformation#Ivermectin}}
In December 2020, Chair of the [[Senate Homeland Security Committee|US Senate Homeland Security Committee]] [[Ron Johnson (Wisconsin politician)|Ron Johnson]] used a Senate hearing to promote fringe theories about COVID-19.<ref name=nytqiu>{{Cite news|last=Qiu|first=Linda|date=17 December 2020|title=The election is over, but Ron Johnson keeps promoting false claims of fraud.|language=en-US|work=The New York Times|url=https://www.nytimes.com/2020/12/16/technology/the-election-is-over-but-ron-johnson-keeps-promoting-false-claims-of-fraud.html|access-date=18 December 2020|issn=0362-4331}}</ref> Among the witnesses was [[Pierre Kory]], a pulmonary and critical care doctor, who erroneously described ivermectin as "miraculous" and as a "wonder drug" to be used against COVID-19. Video footage of his statements went viral on social media, receiving over one million views as of 11 December 2020.<ref name=ap11d>{{cite web |author=Beatrice Dupuy |date=11 December 2020 |publisher=AP News |type=Fact check |title=No evidence ivermectin is a miracle drug against COVID-19 |url=https://apnews.com/article/fact-checking-afs:Content:9768999400}}</ref>
In December 2020, Chair of the [[Senate Homeland Security Committee|US Senate Homeland Security Committee]] [[Ron Johnson (Wisconsin politician)|Ron Johnson]] used a Senate hearing to promote fringe theories about COVID-19.<ref name=nytqiu>{{Cite news|last=Qiu|first=Linda|date=17 December 2020|title=The election is over, but Ron Johnson keeps promoting false claims of fraud.|language=en-US|work=The New York Times|url=https://www.nytimes.com/2020/12/16/technology/the-election-is-over-but-ron-johnson-keeps-promoting-false-claims-of-fraud.html|access-date=18 December 2020|issn=0362-4331}}</ref> Among the witnesses{{What|reason=Witnesses of what?|date=May 2021}} was [[Pierre Kory]], a pulmonary and critical care doctor, who erroneously described ivermectin as "miraculous" and as a "wonder drug" to be used against COVID-19. Video footage of his statements went viral on social media, receiving over one million views as of 11 December 2020.<ref name=ap11d>{{cite web |author=Beatrice Dupuy |date=11 December 2020 |publisher=AP News |type=Fact check |title=No evidence ivermectin is a miracle drug against COVID-19 |url=https://apnews.com/article/fact-checking-afs:Content:9768999400}}</ref>


==Research==
==Research==

Revision as of 07:51, 15 May 2021

Ivermectin
Clinical data
Trade namesStromectol, Soolantra, Sklice, others
AHFS/Drugs.comSystemic Monograph
Topical Monograph
MedlinePlusa607069
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability–
Protein binding93%
MetabolismLiver (CYP450)
Elimination half-life18 hours
ExcretionFeces; <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 InfoCard100.067.738 Edit this at Wikidata
Chemical and physical data
FormulaC
48H
74O
14 (22,23-dihydroavermectin B1a)
C
47H
72O
14 (22,23-dihydroavermectin B1b)
Molar mass875.106 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 checkY
  • Key:SPBDXSGPUHCETR-JFUDTMANSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Ivermectin is a medication used to treat many types of parasite infestations.[3] In humans, this includes head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis, and lymphatic filariasis.[3][4][5][6] In veterinary medicine, it is used to prevent and treat heartworm and acariasis, among other indications.[5] It can be taken by mouth or applied to the skin for external infestations.[3][7]

Common side effects include fever, itching, and skin rash when taken by mouth,[3] and red eyes, dry skin, and burning skin when used topically for head lice.[8] It is unclear if it is safe for use during pregnancy, but is probably acceptable for use during breastfeeding.[9] It belongs to the avermectin family of medications.[3] It works through many mechanisms of action that result in death of the targeted parasites.[3]

Ivermectin was discovered in 1975 and came into medical use in 1981.[10][11] It is on the World Health Organization's List of Essential Medicines.[12] Ivermectin is FDA-approved as an antiparasitic agent.[13]

During the 2020 COVID-19 pandemic misinformation was widely spread claiming that ivermectin was beneficial for treating and preventing COVID-19. As of 2021 no reliable evidence exist to back up such claims.[14]

Medical uses

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

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.[15] For river blindness, a single oral dose of ivermectin (150 micrograms per kilogram of body weight) clears the body of larval Onchocerca volvulus worms for several months, preventing transmission and disease progression.[15] 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.[16] For lymphatic filariasis, oral ivermectin (200 micrograms per kilogram body weight) is part of a combination treatment given annually: ivermectin, diethylcarbamazine citrate and albendazole in places without onchocerciasis; ivermectin and albendazole in places with onchocerciasis.[17][note 1]

The World Health Organization considers ivermectin the "drug of choice" for strongyloidiasis.[19] Most cases are treated with two daily doses of oral ivermectin (200 μg per kg body weight), while severe infections are treated with five to seven days of ivermectin.[15] Ivermectin is also the primary treatment for Mansonella ozzardi and cutaneous larva migrans.[20][21] The U.S. Centers for Disease Control recommends ivermectin, albendazole, or mebendazole as treatments for ascariasis.[22][note 2] Ivermectin is sometimes added to albendazole or mebendazole for whipworm treatment, and is considered a second-line treatment for gnathostomiasis.[21][26]

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. 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.[27][28] For severe "crusted scabies", the Centers for Disease Control recommends up to seven doses of ivermectin over the course of a month, along with a topical antiparasitic.[28] Both head lice and pubic lice can be treated with oral ivermectin, a 0.5% ivermection lotion applied directly to the affected area, or various other insecticides.[29][30] Ivermectin is also used to treat rosacea and blepharitis, both of which can be caused or exacerbated by Demodex folliculorum mites.[31][32]

Contraindications

Ivermectin is contraindicated in children under the age of five or those who weigh less than 15 kilograms (33 pounds),[33] and individuals with liver or kidney disease.[34] Ivermectin is secreted in very low concentration in breast milk.[35] It remains unclear if ivermectin is safe during pregnancy.[36]

Adverse effects

Serious adverse events following ivermectin treatment are more common in people with very high burdens of larval Loa loa worms in their blood.[37] 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.[37]

The main concern is neurotoxicity, which in most mammalian species may manifest as central nervous system depression, and consequent ataxia, as might be expected from potentiation of inhibitory GABA-ergic synapses.

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.[38]

For dogs, the insecticide spinosad may have the effect of increasing the toxicity of ivermectin.[39]

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​.

Mechanism of action

Ivermectin and its related drugs act by interfering with nerve and muscle function of helminths and insects.[40] The drug binds to glutamate-gated chloride channels that are common to invertebrate nerve and muscle cells.[41] Ivermectin binding pushes these channels open, increasing the flow of chloride ions and hyper-polarizing the cell membranes.[41][40] This hyperpolarization paralyzes the affected tissue, eventually killing the invertebrate.[41] In mammals (including humans) glutamate-gated chloride channels are restricted to the brain and spinal cord; ivermectin cannot cross the blood-brain barrier and so it does not make it to the brain to affect mammalian channels.[41]

Pharmacokinetics

Ivermectin can be given by mouth, topically, or via injection. It does not readily cross the blood–brain barrier of mammals due to the presence of P-glycoprotein[42] (the MDR1 gene mutation affects function of this protein). 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.

Ecotoxicity

Field studies have demonstrated the dung of animals treated with ivermectin supports a significantly reduced diversity of invertebrates, and the dung persists longer.[43]

Chemistry

Avermectins producted 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.[44][45][46]

History

The avermectin family of compounds was discovered by Satoshi Ōmura of Kitasato University and William Campbell of Merck. In 1970, Ōmura isolated unusual Streptomyces bacteria from the soil near a golf course along the south east coast of Honshu, Japan.[46] Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm Heligmosomoides polygyrus.[46] 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').[46] Of the various avermectins, Campbell's group found the compound "avermectin B1" to be the most potent when taken orally.[46] 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".[46][47]

Ivermectin was introduced in 1981.[48] 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".[49]

Society and culture

Cost

The initial price proposed by Merck in 1987 was US$6 per treatment, not affordable for most patients in Africa.[50] The company donated hundreds of millions of courses of treatments since 1988 in more than 30 countries.[50] Between 1995 and 2010 the program using donated ivermectin to prevent river blindness is estimated to have prevented seven million years of disability whilst costing US$257 million.[51]

As of 2019, the cost effectiveness of treating scabies and lice with ivermectin has not been studied.[52][53]

As of 2019, ivermectin tablets in the United States were the least expensive treatment option for lice in children at about US$10.[54] The hair lotion, however, costs[which?] about US$300 for a course of treatment.[54]

Brand names

Ivermectin is available as a generic prescription drug in the U.S. in a 3 mg tablet formulation.[55] It is also sold under the brand names Heartgard, Sklice[56] and Stromectol[57] in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT[58] 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 as Soolantra. While in development, it was assigned the code MK-933 by Merck.[59]

COVID-19 misinformation

Further information: COVID-19 misinformation § Ivermectin

In December 2020, Chair of the US Senate Homeland Security Committee Ron Johnson used a Senate hearing to promote fringe theories about COVID-19.[60] Among the witnesses[clarification needed] was Pierre Kory, a pulmonary and critical care doctor, who erroneously described ivermectin as "miraculous" and as a "wonder drug" to be used against COVID-19. Video footage of his statements went viral on social media, receiving over one million views as of 11 December 2020.[61]

Research

COVID-19

This section is an excerpt from COVID-19 drug repurposing research § Ivermectin.[edit]
Template loop detected: Template:Excerpt

Tropical diseases

Ivermectin is being studied as a potential antiviral agent against chikungunya and yellow fever.[62]

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.[63][64] 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 and safety of ivermectin for prophylaxis or treatment of malaria.[65] Mass drug administration of a population with ivermectin for purposes of treating/preventing nematode infestation is effective for eliminating malaria-bearing mosquitos and thereby reducing infection with residual malaria parasites.[66]

Moxidectin has been approved by the FDA for use in people with river blindness, 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.[67][68]

Bedbugs: There is tentative evidence that ivermectin kills bedbugs, as part of integrated pest management for bedbug infestations.[69][70][71] Such use however may require a prolonged course of treatment which is of unclear safety.[72]

NAFLD

In 2013, this antiparasitic drug was demonstrated as a novel ligand of farnesoid X receptor (FXR),[73][74] a therapeutic target for nonalcoholic fatty liver disease.[75]

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 effective in killing some, but not all, of these parasites.[citation needed]

In dogs it is routinely used as prophylaxis against heartworm.[76]

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.[77] 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.[78][79] Clinical evidence suggests kittens are susceptible to ivermectin toxicity.[80] A 0.01% ivermectin topical preparation for treating ear mites in cats is available.[81]

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.[82]

See also

Notes

  1. ^ In people with onchocerciasis, diethylcarbamazine citrate can cause a dangerous set of side effects called Mazzotti reaction. Due to this, diethylcarbamazine citrate is avoided in places where onchocerciasis is common.[18]
  2. ^ This recommendation is not universal. The World Health Organization recommends ascariasis be treated with mebendazole or pyrantel pamoate,[23] while the textbook Parasitic Diseases recommends albendazole or mebendazole.[24] A 2020 Cochrane review concluded that the three drugs are equally safe and effective for treating ascariasis.[25]

References

  1. ^ "FDA Approves Lotion for Nonprescription Use to Treat Head Lice". U.S. Food and Drug Administration (FDA) (Press release). October 27, 2020. Retrieved October 27, 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  2. ^ "List of nationally authorised medicinal products", European Medicines Agency, 26 November 2020.
  3. ^ a b c d e f "Ivermectin". The American Society of Health-System Pharmacists. Archived from the original on January 3, 2016. Retrieved January 16, 2016.
  4. ^ Sneader W (2005). Drug Discovery a History. Chichester: John Wiley & Sons. p. 333. ISBN 978-0-470-01552-0.
  5. ^ a b Saunders Handbook of Veterinary Drugs: Small and Large Animal (4 ed.). Elsevier Health Sciences. 2015. p. 420. ISBN 978-0-323-24486-2. Archived from the original on January 31, 2016.
  6. ^ CDC-Centers for Disease Control and Prevention (August 23, 2019). "Ascariasis - Resources for Health Professionals". www.cdc.gov. Retrieved December 28, 2019.
  7. ^ Panahi Y, Poursaleh Z, Goldust M (2015). "The efficacy of topical and oral ivermectin in the treatment of human scabies" (PDF). Annals of Parasitology. 61 (1): 11–16. PMID 25911032.
  8. ^ "Ivermectin (topical)". The American Society of Health-System Pharmacists. July 27, 2020. Retrieved January 16, 2021.
  9. ^ "Ivermectin Levels and Effects while Breastfeeding". Drugs.com. Archived from the original on January 1, 2016. Retrieved January 16, 2016.
  10. ^ Mehlhorn H (2008). Encyclopedia of parasitology (3rd ed.). Berlin: Springer. p. 646. ISBN 978-3-540-48994-8. Archived from the original on June 26, 2020.
  11. ^ Vercruysse J, Rew RS, eds. (2002). Macrocyclic lactones in antiparasitic therapy. Oxon, UK: CABI Pub. p. Preface. ISBN 978-0-85199-840-4. Archived from the original on January 31, 2016.
  12. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  13. ^ Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, et al. (December 2020). "A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness". International Journal of Infectious Diseases. 103: 214–216. doi:10.1016/j.ijid.2020.11.191. PMC 7709596. PMID 33278625.
  14. ^ "EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials". European Medicines Agency. March 22, 2021.{{cite web}}: CS1 maint: url-status (link)
  15. ^ a b c Ashour DS (August 2019). "Ivermectin: From theory to clinical application". Int J Antimicrob Agents. 54 (2): 134–142. doi:10.1016/j.ijantimicag.2019.05.003. PMID 31071469.
  16. ^ "Onchocerciasis". World Health Organization. June 14, 2019. Retrieved January 11, 2021.
  17. ^ "Lymphatic filariasis". World Health Organization. March 2, 2020. Retrieved January 11, 2021.
  18. ^ Babalola OE (2011). "Ocular onchocerciasis: current management and future prospects". Clin Ophthalmol. 5: 1479–91. doi:10.2147/OPTH.S8372. PMC 3206119. PMID 22069350.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ "Strongyloidiasis". World Health Organization. Retrieved January 25, 2021.
  20. ^ Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA (2019). "26. Other Nematodes of Medical Imortance". Parasitic Diseases (PDF) (7 ed.). New York: Parasites Without Borders. p. 201. Retrieved January 26, 2021.
  21. ^ a b Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA (2019). "27. Aberrant Nematode Infections". Parasitic Diseases (PDF) (7 ed.). New York: Parasites Without Borders. p. 201. Retrieved January 26, 2021.
  22. ^ "Ascariasis - Resources for Health Professionals". U.S. Centers for Disease Control and Prevention. May 20, 2020. Retrieved February 10, 2021.
  23. ^ "Water related diseases - Ascariasis". World Health Organization. Retrieved February 10, 2021.
  24. ^ Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA (2019). "18. Ascaris lumbricoides". Parasitic Diseases (PDF) (7 ed.). New York: Parasites Without Borders. p. 211. Retrieved January 26, 2021.
  25. ^ Conterno LO, Turchi MD, Corrêa I, Monteiro de Barros Almeida RA (April 2020). "Anthelmintic drugs for treating ascariasis". Cochrane Database Syst Rev. 4: CD010599. doi:10.1002/14651858.CD010599.pub2. PMC 7156140. PMID 32289194.
  26. ^ Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA (2019). "17. Trichuris trichiura". Parasitic Diseases (PDF) (7 ed.). New York: Parasites Without Borders. p. 201. Retrieved January 26, 2021.
  27. ^ Thomas C, Coates SJ, Engelman D, Chosidow O, Chang AY (March 2020). "Ectoparasites: Scabies". J Am Acad Dermatol. 82 (3): 533–548. doi:10.1016/j.jaad.2019.05.109. PMID 31310840.
  28. ^ a b "Scabies - Medications". U.S. Centers for Disease Control and Prevention. Retrieved February 11, 2021.
  29. ^ Gunning K, Kiraly B, Pippitt K (May 2019). "Lice and Scabies: Treatment Update". Am Fam Physician. 99 (10): 635–642. PMID 31083883.
  30. ^ "Pubic "Crab" Lice - Treatment". U.S. Centers for Disease Control and Prevention. Retrieved February 11, 2021.
  31. ^ vaan Zuuren EJ (November 2017). "Rosacea". N Engl J Med. 377 (18): 1754–1764. doi:10.1056/NEJMcp1506630. PMID 29091565.
  32. ^ Elston CA, Elston DM (2014). "Demodex mites". Clin Dermatol. 32 (6): 739–43. doi:10.1016/j.clindermatol.2014.02.012. PMID 25441466.
  33. ^ Dourmishev AL, Dourmishev LA, Schwartz RA (December 2005). "Ivermectin: pharmacology and application in dermatology". International Journal of Dermatology. 44 (12): 981–8. doi:10.1111/j.1365-4632.2004.02253.x. PMID 16409259. S2CID 27019223.
  34. ^ Heukelbach J, Winter B, Wilcke T, Muehlen M, Albrecht S, de Oliveira FA, Kerr-Pontes LR, Liesenfeld O, Feldmeier H (August 2004). "Selective mass treatment with ivermectin to control intestinal helminthiases and parasitic skin diseases in a severely affected population". Bulletin of the World Health Organization. 82 (8): 563–71. PMC 2622929. PMID 15375445.
  35. ^ Koh YP, Tian EA, Oon HH (September 2019). "New changes in pregnancy and lactation labelling: Review of dermatologic drugs". Int J Womens Dermatol. 5 (4): 216–226. doi:10.1016/j.ijwd.2019.05.002. PMC 6831768. PMID 31700976.
  36. ^ Nicolas P, Maia MF, Bassat Q, Kobylinski KC, Monteiro W, Rabinovich NR, Menéndez C, Bardají A, Chaccour C (January 2020). "Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis". Lancet Glob Health. 8 (1): e92–e100. doi:10.1016/S2214-109X(19)30453-X. PMID 31839144.
  37. ^ a b Pion SD, Tchatchueng-Mbougua JB, Chesnais CB, Kamgno J, Gardon J, Chippaux JP, et al. (April 2019). "Effect of a Single Standard Dose (150–200 μg/kg) of Ivermectin on Loa loa Microfilaremia: Systematic Review and Meta-analysis". Open Forum Infectious Diseases. 6 (4): ofz019. doi:10.1093/ofid/ofz019. PMC 6449757. PMID 30968052.
  38. ^ Goodman and Gilman's The Pharmacological Basis of Therapeutics], 11th edition, pages 1084–1087.
  39. ^ "COMFORTIS® and ivermectin interaction Safety Warning Notification". U.S. Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM). Archived from the original on August 29, 2009.
  40. ^ a b Martin RJ, Robertson AP, Choudhary S (January 2021). "Ivermectin: An Anthelmintic, an Insecticide, and Much More". Trends Parasitol. 37 (1): 48–64. doi:10.1016/j.pt.2020.10.005. PMC 7853155. PMID 33189582. S2CID 226972704.{{cite journal}}: CS1 maint: PMC embargo expired (link)
  41. ^ a b c d Omura S, Crump A (September 2014). "Ivermectin: panacea for resource-poor communities?". Trends Parasitol. 30 (9): 445–55. doi:10.1016/j.pt.2014.07.005. PMID 25130507.
  42. ^ Borst P, Schinkel AH (June 1996). "What have we learnt thus far from mice with disrupted P-glycoprotein genes?". European Journal of Cancer. 32A (6): 985–90. doi:10.1016/0959-8049(96)00063-9. PMID 8763339.
  43. ^ Iglesias LE, Saumell CA, Fernández AS, Fusé LA, Lifschitz AL, Rodríguez EM, Steffan PE, Fiel CA (December 2006). "Environmental impact of ivermectin excreted by cattle treated in autumn on dung fauna and degradation of faeces on pasture". Parasitology Research. 100 (1): 93–102. doi:10.1007/s00436-006-0240-x. PMID 16821034. S2CID 28765870.
  44. ^ Lasota, J. A.; Dybas, R. A. (1991). "Avermectins, A Novel Class of Compounds: Implications for Use in Arthropod Pest Control". Annual Review of Entomology. 36: 91–117. doi:10.1146/annurev.en.36.010191.000515. PMID 2006872.
  45. ^ Jansson, R. K.; Dybas, R. A. (1998). "Avermectins: Biochemical Mode of Action, Biological Activity and Agricultural Importance". Insecticides with Novel Modes of Action. Applied Agriculture. Berlin, Heidelberg: Springer. pp. 152–170. doi:10.1007/978-3-662-03565-8_9. ISBN 978-3-642-08314-3.
  46. ^ a b c d e f Laing R, Gillan V, Devaney E (June 2017). "Ivermectin - Old Drug, New Tricks?". Trends Parasitol. 33 (6): 463–472. doi:10.1016/j.pt.2017.02.004. PMC 5446326. PMID 28285851.
  47. ^ Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA (August 1983). "Ivermectin: a potent new antiparasitic agent". Science. 221 (4613): 823–8. Bibcode:1983Sci...221..823C. doi:10.1126/science.6308762. PMID 6308762.
  48. ^ Campbell WC, Burg RW, Fisher MH, Dybas RA (June 26, 1984). "Chapter 1: The discovery of ivermectin and other avermectins". Pesticide Synthesis Through Rational Approaches. ACS Symposium Series. Vol. 255. American Chemical Society. pp. 5–20. doi:10.1021/bk-1984-0255.ch001. ISBN 978-0-8412-1083-7.
  49. ^ "The Nobel Prize in Physiology or Medicine 2015" (PDF). Nobel Foundation. Archived from the original (PDF) on October 6, 2015. Retrieved October 7, 2015.
  50. ^ a b Crump A, Ōmura S (2011). "Ivermectin, 'wonder drug' from Japan: the human use perspective". Proceedings of the Japan Academy. Series B, Physical and Biological Sciences. 87 (2): 13–28. Bibcode:2011PJAB...87...13C. doi:10.2183/pjab.87.13. PMC 3043740. PMID 21321478.
  51. ^ Omaswa F, Crisp N (2014). African Health Leaders: Making Change and Claiming the Future. OUP Oxford. p. PT158. ISBN 9780191008412.
  52. ^ Chiu S, Argaez C (2019). Ivermectin for Parasitic Skin Infections of Scabies: A Review of Comparative Clinical Effectiveness, Cost-Effectiveness, and Guidelines. CADTH Rapid Response Reports. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. PMID 31424718.
  53. ^ Young C, Argáez C (2019). Ivermectin for Parasitic Skin Infections of Lice: A Review of Comparative Clinical Effectiveness, Cost-Effectiveness, and Guidelines. CADTH Rapid Response Reports. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. PMID 31487135.
  54. ^ a b Kliegman RM, St Geme J (2019). Nelson Textbook of Pediatrics E-Book. Elsevier Health Sciences. p. 3575. ISBN 9780323568883.
  55. ^ U.S. FDA. "Abbreviated New Drug Application (ANDA): 204154". Drugs@FDA: FDA Approved Drug Products. U.S. Food and Drug Administration. Retrieved August 18, 2018.
  56. ^ "Sklice- ivermectin lotion". DailyMed. November 9, 2017. Retrieved October 28, 2020.
  57. ^ "Stromectol- ivermectin tablet". DailyMed. December 15, 2019. Retrieved October 28, 2020.
  58. ^ Adhikari S (May 27, 2014). "Alive Pharmaceutical (P) LTD.: Iver-DT". Alive Pharmaceutical (P) LTD. Archived from the original on March 4, 2016. Retrieved October 7, 2015.
  59. ^ Pampiglione S, Majori G, Petrangeli G, Romi R (1985). "Avermectins, MK-933 and MK-936, for mosquito control". Transactions of the Royal Society of Tropical Medicine and Hygiene. 79 (6): 797–9. doi:10.1016/0035-9203(85)90121-X. PMID 3832491.
  60. ^ Qiu, Linda (December 17, 2020). "The election is over, but Ron Johnson keeps promoting false claims of fraud". The New York Times. ISSN 0362-4331. Retrieved December 18, 2020.
  61. ^ Beatrice Dupuy (December 11, 2020). "No evidence ivermectin is a miracle drug against COVID-19" (Fact check). AP News.
  62. ^ Varghese FS, Kaukinen P, Gläsker S, Bespalov M, Hanski L, Wennerberg K, Kümmerer BM, Ahola T (February 2016). "Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses". Antiviral Research. 126: 117–24. doi:10.1016/j.antiviral.2015.12.012. PMID 26752081.
  63. ^ Chaccour C, Hammann F, Rabinovich NR (April 2017). "Ivermectin to reduce malaria transmission I. Pharmacokinetic and pharmacodynamic considerations regarding efficacy and safety". Malaria Journal. 16 (1): 161. doi:10.1186/s12936-017-1801-4. PMC 5402169. PMID 28434401.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  64. ^ Siewe Fodjo JN, Kugler M, Hotterbeekx A, Hendy A, Van Geertruyden JP, Colebunders R (August 2019). "Would ivermectin for malaria control be beneficial in onchocerciasis-endemic regions?". Infectious Diseases of Poverty. 8 (1): 77. doi:10.1186/s40249-019-0588-7. PMC 6706915. PMID 31439040.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  65. ^ Navarro M, Camprubí D, Requena-Méndez A, Buonfrate D, Giorli G, Kamgno J, Gardon J, Boussinesq M, Muñoz J, Krolewiecki A (April 2020). "Safety of high-dose ivermectin: a systematic review and meta-analysis". J. Antimicrob. Chemother. 75 (4): 827–834. doi:10.1093/jac/dkz524. PMID 31960060.
  66. ^ Tizifa TA, Kabaghe AN, McCann RS, van den Berg H, Van Vugt M, Phiri KS (2018). "Prevention Efforts for Malaria". Curr Trop Med Rep. 5 (1): 41–50. doi:10.1007/s40475-018-0133-y. PMC 5879044. PMID 29629252.
  67. ^ Maheu-Giroux M, Joseph SA (August 2018). "Moxidectin for deworming: from trials to implementation". The Lancet. Infectious Diseases. 18 (8): 817–819. doi:10.1016/S1473-3099(18)30270-6. PMID 29858152.
  68. ^ Boussinesq M (October 2018). "A new powerful drug to combat river blindness". Lancet. 392 (10154): 1170–1172. doi:10.1016/S0140-6736(18)30101-6. PMID 29361336. Open access icon
  69. ^ Crump A (May 2017). "Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations". J. Antibiot. 70 (5): 495–505. doi:10.1038/ja.2017.11. PMID 28196978.
  70. ^ Ōmura S (August 2016). "A Splendid Gift from the Earth: The Origins and Impact of the Avermectins (Nobel Lecture)". Angew. Chem. Int. Ed. Engl. 55 (35): 10190–209. doi:10.1002/anie.201602164. PMID 27435664.
  71. ^ James WD, Elston D, Berger T, Neuhaus I (2015). Andrews' Diseases of the Skin: Clinical Dermatology. Elsevier Health Sciences. p. 439. ISBN 9780323319690. Ivermectin treatment is emerging as a potential ancillary measure.
  72. ^ Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I (2017). Treatment of Skin Disease: Comprehensive Therapeutic Strategies. Elsevier Health Sciences. p. 89. ISBN 9780702069130.
  73. ^ Carotti A, Marinozzi M, Custodi C, Cerra B, Pellicciari R, Gioiello A, Macchiarulo A (2014). "Beyond bile acids: targeting Farnesoid X Receptor (FXR) with natural and synthetic ligands". Current Topics in Medicinal Chemistry. 14 (19): 2129–42. doi:10.2174/1568026614666141112094058. PMID 25388537.
  74. ^ Jin L, Feng X, Rong H, Pan Z, Inaba Y, Qiu L, et al. (2013). "The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism". Nature Communications. 4: 1937. Bibcode:2013NatCo...4.1937J. doi:10.1038/ncomms2924. PMID 23728580.
  75. ^ Kim SG, Kim BK, Kim K, Fang S (December 2016). "Bile Acid Nuclear Receptor Farnesoid X Receptor: Therapeutic Target for Nonalcoholic Fatty Liver Disease". Endocrinology and Metabolism. 31 (4): 500–504. doi:10.3803/EnM.2016.31.4.500. PMC 5195824. PMID 28029021.
  76. ^ Papich MG (January 1, 2016). "Ivermectin". In Papich MG (ed.). Saunders Handbook of Veterinary Drugs. W.B. Saunders. pp. 420–423. doi:10.1016/B978-0-323-24485-5.00323-5. ISBN 978-0-323-24485-5. Retrieved April 7, 2020. {{cite book}}: |work= ignored (help)
  77. ^ Dowling P (December 2006). "Pharmacogenetics: it's not just about ivermectin in collies". Can. Vet. J. 47 (12): 1165–8. PMC 1636591. PMID 17217086.
  78. ^ "MDR1 FAQs". Australian Shepherd Health & Genetics Institute, Inc. Archived from the original on December 13, 2007.
  79. ^ "Multidrug Sensitivity in Dogs". Washington State University's College of Veterinary Medicine. Archived from the original on June 23, 2015.
  80. ^ Frischke H, Hunt L (April 1991). "Alberta. Suspected ivermectin toxicity in kittens". The Canadian Veterinary Journal. 32 (4): 245. PMC 1481314. PMID 17423775.
  81. ^ "Acarexx". Boehringer Ingelheim. April 11, 2016.
  82. ^ Klingenberg R (2007). Understanding reptile parasites: from the experts at Advanced Vivarium Systems. Irvine, Calif: Advanced Vivarium Systems. ISBN 978-1882770908.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Ivermectin&oldid=1023240281"