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Ivermectin

Clinical data
Pronunciation	/ˌaɪvərˈmɛktɪn/, EYE-vər-MEK-tin
Trade names	Stromectol, others
Other names	MK-933
AHFS/Drugs.com	Systemic Monograph Topical Monograph
MedlinePlus	a607069
License data	US DailyMed: Ivermectin
Pregnancy category	AU: B3
Routes of administration	By mouth, topical
ATC code	D11AX22 (WHO) , P02CF01 (WHO), QP54AA01 (WHO), QS02QA03 (WHO)
Legal status
Legal status	CA: ℞-only US: ℞-only  EU: Rx-only
Pharmacokinetic data
Bioavailability	not determined
Protein binding	93%
Metabolism	Liver (CYP450)
Elimination half-life	38.9 ± 20.8 h
Excretion	Feces; <1% urine
Identifiers
IUPAC name 22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
CAS Number	70288-86-7 71827-03-7
PubChem CID	6321424
DrugBank	DB00602
ChemSpider	7988461
UNII	8883YP2R6D
KEGG	D00804
ChEBI	CHEBI:6078
ChEMBL	ChEMBL1200633
PDB ligand	IVM (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID7040235
ECHA InfoCard	100.067.738
Chemical and physical data
Formula	C 48H 74O 14 (22,23-dihydroavermectin B1a) C 47H 72O 14 (22,23-dihydroavermectin B1b)
Molar mass	875.106 g·mol (22,23-dihydroavermectin B1a) 861.079 g·mol (22,23-dihydroavermectin B1b)
3D model (JSmol)
SMILES CC(C)1(CC2(O1)C3C(O2)C/C=C(/((/C=C/C=C/4\CO54((C=C(5O)C)C(=O)O3)O)C)O6C(((O6)C)O7C(((O7)C)O)OC)OC)\C)C.C1CC2(C3C(O2)C/C=C(/((/C=C/C=C/4\CO54((C=C(5O)C)C(=O)O3)O)C)O6C(((O6)C)O7C(((O7)C)O)OC)OC)\C)O1C(C)C
InChI 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 Key:SPBDXSGPUHCETR-JFUDTMANSA-N
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Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through many mechanisms to kill the targeted parasites, and can be taken by mouth, or applied to the skin for external infestations. It belongs to the avermectin family of medications.

William Campbell and Satoshi Ōmura were awarded the 2015 Nobel Prize in Physiology or Medicine for its discovery and applications. It is on the World Health Organization's List of Essential Medicines, and is approved by the U.S. Food and Drug Administration as an antiparasitic agent. In 2022, it was the 314th most commonly prescribed medication in the United States, with more than 200,000 prescriptions. It is available as a generic medicine.

Misinformation has been widely spread claiming that ivermectin is beneficial for treating and preventing COVID-19. Such claims are not backed by credible scientific evidence. Multiple major health organizations, including the U.S. Food and Drug Administration, the U.S. Centers for Disease Control and Prevention, the European Medicines Agency, and the World Health Organization have advised that ivermectin is not recommended for the treatment of COVID-19.

Medical uses

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

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. 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.

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

Mites and insects

Ivermectin is also used to treat infection with parasitic arthropods. Scabies – infestation with the mite Sarcoptes scabiei – is most commonly treated with topical permethrin or oral ivermectin. A single application of permethrin is more efficacious than a single treatment of ivermectin. For most scabies cases, ivermectin is used in a two-dose regimen: 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. 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.

For severe "crusted scabies", where the parasite burden is orders of magnitude higher than usual, the U.S. Centers for Disease Control and Prevention (CDC) recommends up to seven doses of ivermectin over the course of a month, along with a topical antiparasitic. 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. Ivermectin is also used to treat rosacea and blepharitis, both of which can be caused or exacerbated by Demodex folliculorum mites.

Contraindications

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

Adverse effects

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

Ivermectin is considered relatively free of toxicity in standard doses (around 300 μg/kg). Based on the data drug safety sheet for ivermectin, 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. 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 even death, as might be expected from potentiation of inhibitory chloride channels.

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.

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

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, 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), 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.

Pharmacology

Mechanism of action

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. 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.

Pharmacokinetics

Ivermectin can be given by mouth, topically, or via injection. Oral doses are absorbed into systemic circulation; the alcoholic solution form is more orally available than tablet and capsule forms. Ivermectin is widely distributed in the body.

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). 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.

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.

Chemistry

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.

Ivermectin is a macrocyclical lactone.

History

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. 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".

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."

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. 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. They found it to be highly safe and effective, 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. 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".

Society and culture

COVID-19 misinformation

Early in the COVID-19 pandemic, laboratory research suggested ivermectin might have a role in preventing or treating COVID-19. Online misinformation campaigns and advocacy boosted the drug's profile among the public. While scientists and physicians largely remained skeptical, some nations adopted ivermectin as part of their pandemic-control efforts. Some people, desperate to use ivermectin without a prescription, took veterinary preparations, which led to shortages of supplies of ivermectin for animal treatment. The FDA responded to this situation by saying "You are not a horse" in a tweet to draw attention to the issue, for which they were later sued by three ivermectin-prescribing doctors.

Economics

The initial price proposed by Merck in 1987 was US$6 per treatment, which was unaffordable for patients who most needed ivermectin. 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 US$257 million.

Ivermectin is considered an inexpensive drug. As of 2019, ivermectin tablets (Stromectol) in the United States were the least expensive treatment option for lice in children at approximately US$9.30, while Sklice, an ivermectin lotion, cost around US$300 for 120 mL (4 US fl oz).

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

Brand names

It is sold under the brand names Heartgard, Sklice and Stromectol in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT 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. While in development, it was assigned the code MK-933 by Merck.

Research

Parasitic disease

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

Ivermectin has also been tested on zebrafish infected with Pseudocapillaria tomentosa.

Tropical diseases

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. A direct effect on malaria parasites could not be shown in an experimental infection of volunteers with Plasmodium falciparum. 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. 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. 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. 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.

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

NAFLD

In 2013, ivermectin was demonstrated as a novel ligand of the farnesoid X receptor, a therapeutic target for nonalcoholic fatty liver disease (NAFLD).

COVID-19

During the COVID-19 pandemic, ivermectin was researched for possible utility in preventing and treating COVID-19, but no good evidence of benefit was found.

Veterinary use

Ivermectin is routinely used to control parasitic worms in the gastrointestinal tract of ruminant animals. These parasites normally enter the animal when it is grazing, pass the bowel, and set and mature in the intestines, after which they produce eggs that leave the animal via its droppings and can infest new pastures. Ivermectin is only effective in killing some of these parasites, because of an increase in anthelmintic resistance. This resistance has arisen from the persistent use of the same anthelmintic drugs for the past 40 years. 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.

In dogs, ivermectin is routinely used as prophylaxis against heartworm. 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. 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. For dogs, the insecticide spinosad may have the effect of increasing the toxicity of ivermectin.

A 0.01% ivermectin topical preparation for treating ear mites in cats is available. Clinical evidence suggests 7-week-old kittens are susceptible to ivermectin toxicity.

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.

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.

Notes

1. This recommendation is not universal. The World Health Organization recommends ascariasis be treated with mebendazole or pyrantel pamoate, while the textbook Parasitic Diseases recommends albendazole or mebendazole. A 2020 Cochrane review concluded that the three drugs are equally safe and effective for treating ascariasis.

1. New Drug Application Identifier: 50-742/S-022

References

1. "Regulatory Decision Summary for Stromectol". October 23, 2014. Archived from the original on June 7, 2022. Retrieved June 7, 2022.
2. "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. May 4, 2016. Archived from the original on February 20, 2020. Retrieved April 7, 2024.
3. ^ "Stromectol – ivermectin tablet". DailyMed. December 15, 2019. Archived from the original on October 31, 2020. Retrieved October 28, 2020.
4. ^ "Soolantra – ivermectin cream". DailyMed. Archived from the original on July 19, 2021. Retrieved July 18, 2021.
5. "List of nationally authorised medicinal products" (PDF). European Medicines Agency. November 26, 2020. Archived (PDF) from the original on December 28, 2020.
6. ^ Kern C, Müller P, Chaccour C, Liechti ME, Hammann F, Duthaler U (June 2023). "Pharmacokinetics of ivermectin metabolites and their activity against Anopheles stephensi mosquitoes". Malaria Journal. 22 (1): 194. doi:10.1186/s12936-023-04624-0. PMC 10290335. PMID 37355605.
7. ^ Laing R, Gillan V, Devaney E (June 2017). "Ivermectin – Old Drug, New Tricks?". Trends in Parasitology. 33 (6): 463–472. doi:10.1016/j.pt.2017.02.004. PMC 5446326. PMID 28285851.
8. Campbell WC (May 2012). "History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents". Current Pharmaceutical Biotechnology. 13 (6): 853–865. doi:10.2174/138920112800399095. PMID 22039784.
9. ^ 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.
10. ^ Molyneux DH, Ward SA (December 2015). "Reflections on the Nobel Prize for Medicine 2015—The Public Health Legacy and Impact of Avermectin and Artemisinin". Trends in Parasitology. 31 (12): 605–607. doi:10.1016/j.pt.2015.10.008. PMID 26552892.
11. ^ "Ivermectin". The American Society of Health-System Pharmacists. Archived from the original on January 3, 2016. Retrieved January 16, 2016.
12. Sneader W (2005). Drug Discovery a History. Chichester: John Wiley & Sons. p. 333. ISBN 978-0-470-01552-0. Archived from the original on June 15, 2020. Retrieved April 5, 2020.
13. "Ascariasis – Resources for Health Professionals". U.S. Centers for Disease Control and Prevention (CDC). August 23, 2019. Archived from the original on November 21, 2010. Retrieved December 28, 2019.
14. 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. Archived (PDF) from the original on April 4, 2020.
15. ^ "The Nobel Prize in Physiology or Medicine 2015" (PDF). Nobel Foundation. Archived from the original (PDF) on October 6, 2015. Retrieved October 7, 2015.
16. 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.
17. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
18. Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, et al. (February 2021). "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.
19. "Ivermectin Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved August 30, 2024.
20. "Ivermectin: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on November 28, 2021. Retrieved September 26, 2021.
21. "Ivermectin lotion: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on September 26, 2021. Retrieved September 25, 2021.
22. Evershed N, McGowan M, Ball A. "Anatomy of a conspiracy theory: how misinformation travels on Facebook". The Guardian. Archived from the original on March 18, 2023. Retrieved May 26, 2021.
23. "Fact-checking claim about the use of ivermectin to treat COVID-19". PolitiFact. Washington, DC. Archived from the original on March 18, 2023. Retrieved May 26, 2021.
24. Popp M, Reis S, Schießer S, Hausinger RI, Stegemann M, Metzendorf MI, et al. (June 2022). "Ivermectin for preventing and treating COVID-19". The Cochrane Database of Systematic Reviews. 2022 (6): CD015017. doi:10.1002/14651858.CD015017.pub3. eISSN 1465-1858. PMC 9215332. PMID 35726131.
25. ^ "EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials". European Medicines Agency. March 22, 2021. Archived from the original on March 18, 2023. Retrieved May 15, 2021.
26. Garegnani LI, Madrid E, Meza N (April 2021). "Misleading clinical evidence and systematic reviews on ivermectin for COVID-19". BMJ Evidence-Based Medicine. 27 (3): 156–158. doi:10.1136/bmjebm-2021-111678. PMID 33888547.
27. "Why You Should Not Use Ivermectin to Treat or Prevent COVID-19". U.S. Food and Drug Administration (FDA). December 10, 2021. Archived from the original on August 6, 2021. Retrieved July 13, 2021.
28. "Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19" (PDF). CDC Health Alert Network. CDCHAN-00449. August 26, 2021. Archived (PDF) from the original on November 3, 2021. Retrieved January 4, 2022.
29. "EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials". European Medicines Agency. March 22, 2021. Archived from the original on January 17, 2022. Retrieved December 15, 2022.
30. "WHO advises that ivermectin only be used to treat COVID-19 within clinical trials". World Health Organization (WHO). Archived from the original on August 5, 2021. Retrieved January 4, 2022.
31. Crump A (May 2017). "Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations". The Journal of Antibiotics. 70 (5): 495–505. doi:10.1038/ja.2017.11. PMID 28196978. S2CID 24474879. Ivermectin was a revelation. It had a broad spectrum of activity, and was highly efficacious, acting robustly at low doses against a wide variety of nematode, insect, and acarine parasites. It proved to be extremely effective against most common intestinal worms (except tapeworms), could be administered orally, topically or parentally, and showed no signs of cross-resistance with other commonly used anti-parasitic compounds.
32. ^ Ashour DS (August 2019). "Ivermectin: From theory to clinical application". International Journal of Antimicrobial Agents. 54 (2): 134–142. doi:10.1016/j.ijantimicag.2019.05.003. PMID 31071469. S2CID 149445017.
33. "Onchocerciasis". World Health Organization. June 14, 2019. Archived from the original on April 11, 2020. Retrieved January 11, 2021.
34. "Strongyloidiasis". World Health Organization. Archived from the original on October 19, 2021. Retrieved January 25, 2021.
35. Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA (2019). "26. Other Nematodes of Medical Importance". Parasitic Diseases (PDF) (7 ed.). New York: Parasites Without Borders. p. 294. Archived (PDF) from the original on November 24, 2021. Retrieved January 26, 2021.
36. ^ 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. 299. Archived (PDF) from the original on November 24, 2021. Retrieved January 26, 2021.
37. "Ascariasis – Resources for Health Professionals". U.S. Centers for Disease Control and Prevention (CDC). May 20, 2020. Archived from the original on November 21, 2010. Retrieved February 10, 2021.
38. "Water related diseases – Ascariasis". World Health Organization. Archived from the original on October 19, 2021. Retrieved February 10, 2021.
39. 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. Archived (PDF) from the original on November 24, 2021. Retrieved January 26, 2021.
40. Conterno LO, Turchi MD, Corrêa I, Monteiro de Barros Almeida RA (April 2020). "Anthelmintic drugs for treating ascariasis". The Cochrane Database of Systematic Reviews. 2020 (4): CD010599. doi:10.1002/14651858.CD010599.pub2. PMC 7156140. PMID 32289194.
41. 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. Archived (PDF) from the original on November 24, 2021. Retrieved January 26, 2021.
42. Thomas C, Coates SJ, Engelman D, Chosidow O, Chang AY (March 2020). "Ectoparasites: Scabies". Journal of the American Academy of Dermatology. 82 (3): 533–548. doi:10.1016/j.jaad.2019.05.109. PMID 31310840. S2CID 242599732.
43. ^ "Scabies – Medications". U.S. Centers for Disease Control and Prevention (CDC). October 2, 2019. Archived from the original on April 30, 2015. Retrieved February 11, 2021.
44. Craig E (2022). The Itch: Scabies (1st ed.). United Kingdom: Oxford University Press. pp. 146–152. ISBN 978-0-19-284840-6.
45. Gunning K, Kiraly B, Pippitt K (May 2019). "Lice and Scabies: Treatment Update". American Family Physician. 99 (10): 635–642. PMID 31083883.
46. "Pubic "Crab" Lice – Treatment". U.S. Centers for Disease Control and Prevention (CDC). September 12, 2019. Archived from the original on November 12, 2020. Retrieved February 11, 2021.
47. van Zuuren EJ (November 2017). "Rosacea". The New England Journal of Medicine. 377 (18): 1754–1764. doi:10.1056/NEJMcp1506630. PMID 29091565.
48. Elston CA, Elston DM (2014). "Demodex mites". Clinics in Dermatology. 32 (6): 739–743. doi:10.1016/j.clindermatol.2014.02.012. PMID 25441466.
49. "Ivermectin (PIM 292)". inchem.org. InChem. Archived from the original on April 26, 2022. Retrieved April 3, 2022.
50. "Stromectol (ivermectin) dose, indications, adverse effects, interactions". www.pdr.net. Prescribers' Digital Reference. Archived from the original on April 25, 2022. Retrieved April 3, 2022.
51. Dourmishev AL, Dourmishev LA, Schwartz RA (December 2005). "Ivermectin: pharmacology and application in dermatology". International Journal of Dermatology. 44 (12): 981–988. doi:10.1111/j.1365-4632.2004.02253.x. PMID 16409259. S2CID 27019223. Archived from the original on October 19, 2021. Retrieved April 6, 2020.
52. Wilkins AL, Steer AC, Cranswick N, Gwee A (May 2018). "Question 1: Is it safe to use ivermectin in children less than five years of age and weighing less than 15 kg?". Archives of Disease in Childhood. 103 (5): 514–519. doi:10.1136/archdischild-2017-314505. PMID 29463522. S2CID 3441595.
53. "Ivermectin – Drug Monographs – Pediatric Care Online". American Academy of Pediatrics Drug Monographs. August 2021. Archived from the original on June 10, 2022. Retrieved April 2, 2022.
54. Fawcett RS (September 15, 2003). "Ivermectin Use in Scabies". American Family Physician. 68 (6): 1089–1092. ISSN 0002-838X. PMID 14524395. Archived from the original on December 27, 2021. Retrieved April 2, 2022.
55. Koh YP, Tian EA, Oon HH (September 2019). "New changes in pregnancy and lactation labelling: Review of dermatologic drugs". International Journal of Women's Dermatology. 5 (4): 216–226. doi:10.1016/j.ijwd.2019.05.002. PMC 6831768. PMID 31700976.
56. Nicolas P, Maia MF, Bassat Q, Kobylinski KC, Monteiro W, Rabinovich NR, et al. (January 2020). "Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis". The Lancet. Global Health. 8 (1): e92–e100. doi:10.1016/S2214-109X(19)30453-X. PMC 7613514. PMID 31839144.
57. "Ivermectin (topical)". The American Society of Health-System Pharmacists. July 27, 2020. Archived from the original on March 18, 2023. Retrieved January 16, 2021.
58. "Ivermectin Levels and Effects while Breastfeeding". Drugs.com. Archived from the original on January 1, 2016. Retrieved January 16, 2016.
59. ^ Navarro M, Camprubí D, Requena-Méndez A, Buonfrate D, Giorli G, Kamgno J, et al. (April 2020). "Safety of high-dose ivermectin: a systematic review and meta-analysis". The Journal of Antimicrobial Chemotherapy. 75 (4): 827–834. doi:10.1093/jac/dkz524. PMID 31960060.
60. Martin RJ, Robertson AP, Choudhary S (January 2021). "Ivermectin: An Anthelmintic, an Insecticide, and Much More". Trends in Parasitology. 37 (1): 48–64. doi:10.1016/j.pt.2020.10.005. PMC 7853155. PMID 33189582.
61. ^ 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.
62. Martin RJ, Robertson AP, Choudhary S (January 2021). "Ivermectin: An Anthelmintic, an Insecticide, and Much More". Trends in Parasitology. 37 (1): 48–64. doi:10.1016/j.pt.2020.10.005. PMC 7853155. PMID 33189582. Although relatively free from toxicity, ivermectin – when large overdoses are administered – may cross the blood–brain barrier, producing depressant effects on the CNS
63. Campillo JT, Boussinesq M, Bertout S, Faillie JL, Chesnais CB (April 2021). "Serious adverse reactions associated with ivermectin: A systematic pharmacovigilance study in sub-Saharan Africa and in the rest of the World". PLOS Neglected Tropical Diseases. 15 (4): e0009354. doi:10.1371/journal.pntd.0009354. PMC 8087035. PMID 33878105. Few hours after administration: nausea, vomiting, abdominal pain, salivation, tachycardia, hypotension, ataxia, pyramidal signs, binocular diplopia
64. Office of the Commissioner (March 12, 2021). "Why You Should Not Use Ivermectin to Treat or Prevent COVID-19". U.S. Food and Drug Administration (FDA). Archived from the original on August 6, 2021. Retrieved July 13, 2021. You can also overdose on ivermectin, which can cause nausea, vomiting, diarrhea, hypotension (low blood pressure), allergic reactions (itching and hives), dizziness, ataxia (problems with balance), seizures, coma and even death.
65. El-Saber Batiha G, Alqahtani A, Ilesanmi OB, Saati AA, El-Mleeh A, Hetta HF, et al. (August 2020). "Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects". Pharmaceuticals. 13 (8): 196. doi:10.3390/ph13080196. PMC 7464486. PMID 32824399. 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
66. Brunton LL, Lazo JS, Paker KL (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. pp. 1084–87. ISBN 978-0-07-142280-2. OCLC 1037399847.
67. "Ivermectin". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, Maryland: National Institute of Diabetes and Digestive and Kidney Diseases. 2012. PMID 31644227. Archived from the original on March 18, 2023. Retrieved May 30, 2021.
68. ^ Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A (2018). "The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug". American Journal of Cancer Research. 8 (2): 317–331. PMC 5835698. PMID 29511601.
69. Schmith VD, Zhou JJ, Lohmer LR (October 2020). "The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19". Clinical Pharmacology and Therapeutics. 108 (4): 762–765. doi:10.1002/cpt.1889. PMC 7267287. PMID 32378737.
70. "Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19". Centers for Disease Control and Prevention. August 26, 2021. Archived from the original on March 18, 2023. Retrieved September 4, 2021.
71. ^ Martin RJ, Robertson AP, Choudhary S (January 2021). "Ivermectin: An Anthelmintic, an Insecticide, and Much More". Trends in Parasitology. 37 (1): 48–64. doi:10.1016/j.pt.2020.10.005. PMC 7853155. PMID 33189582. S2CID 226972704.
72. ^ Omura S, Crump A (September 2014). "Ivermectin: panacea for resource-poor communities?". Trends in Parasitology. 30 (9): 445–455. doi:10.1016/j.pt.2014.07.005. PMID 25130507.
73. González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ (2008). "The pharmacokinetics and interactions of ivermectin in humans—a mini-review". The AAPS Journal. 10 (1): 42–46. doi:10.1208/s12248-007-9000-9. PMC 2751445. PMID 18446504.
74. 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): 985–990. doi:10.1016/0959-8049(96)00063-9. PMID 8763339.
75. Teare JA, Bush M (December 1983). "Toxicity and efficacy of ivermectin in chelonians" (PDF). Journal of the American Veterinary Medical Association. 183 (11): 1195–1197. PMID 6689009. Archived (PDF) from the original on October 25, 2021. Retrieved October 26, 2021.
76. Lasota JA, Dybas RA (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.
77. Jansson RK, Dybas RA (1998). "Avermectins: Biochemical Mode of Action, Biological Activity and Agricultural Importance". Insecticides with Novel Modes of Action. Applied Agriculture. Berlin, Heidelberg: Springer. pp. 152–70. doi:10.1007/978-3-662-03565-8_9. ISBN 978-3-642-08314-3.
78. Campbell WC (July 1985). "Ivermectin: an update". Parasitology Today. 1 (1): 10–16. doi:10.1016/0169-4758(85)90100-0. PMID 15275618.
79. ^ Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA (August 1983). "Ivermectin: a potent new antiparasitic agent". Science. 221 (4613): 823–828. Bibcode:1983Sci...221..823C. doi:10.1126/science.6308762. PMID 6308762.
80. Campbell WC (January 1, 2005). "Serendipity and new drugs for infectious disease". ILAR Journal. 46 (4): 352–356. doi:10.1093/ilar.46.4.352. PMID 16179743.
81. Omura S, Crump A (December 2004). "The life and times of ivermectin – a success story". Nature Reviews. Microbiology. 2 (12): 984–989. doi:10.1038/nrmicro1048. PMID 15550944. S2CID 22722403.
82. Crump A, Morel CM, Omura S (July 2012). "The onchocerciasis chronicle: from the beginning to the end?". Trends in Parasitology. 28 (7): 280–288. doi:10.1016/j.pt.2012.04.005. PMID 22633470.
83. Geary TG (November 2005). "Ivermectin 20 years on: maturation of a wonder drug". Trends in Parasitology. 21 (11): 530–532. doi:10.1016/j.pt.2005.08.014. PMID 16126457.
84. "The Nobel Prize in Physiology or Medicine 2015". NobelPrize.org. March 18, 2023. Archived from the original on May 23, 2020. Retrieved March 18, 2023.
85. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (June 2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059. PMID 32251768.
86. Woo E (September 28, 2021). "How Covid Misinformation Created a Run on Animal Medicine". New York Times. Archived from the original on January 7, 2022. Retrieved December 23, 2021.
87. Langford C (September 1, 2023). "Fifth Circuit sides with ivermectin-prescribing doctors in their quarrel with the FDA". Courthouse News Service.
88. Popp M, Reis S, Schießer S, Hausinger RI, Stegemann M, Metzendorf MI, et al. (June 2022). "Ivermectin for preventing and treating COVID-19". Cochrane Database Syst Rev (Systematic review). 2022 (6): CD015017. doi:10.1002/14651858.CD015017.pub3. PMC 9215332. PMID 35726131.
89. Reis G, Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, et al. (May 2022). "Effect of Early Treatment with Ivermectin among Patients with Covid-19". N Engl J Med (Randomized controlled trial). 386 (18): 1721–1731. doi:10.1056/NEJMoa2115869. PMC 9006771. PMID 35353979.
90. Lawrence JM, Meyerowitz-Katz G, Heathers JA, Brown NJ, Sheldrick KA (November 2021). "The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable". Nature Medicine. 27 (11): 1853–1854. doi:10.1038/s41591-021-01535-y. PMID 34552263. S2CID 237607620.
91. Schraer R, Goodman J (October 6, 2021). "Ivermectin: How false science created a Covid 'miracle' drug". BBC News. Archived from the original on January 8, 2022. Retrieved December 26, 2021.
92. Melissa Davey (July 15, 2021). "Huge study supporting ivermectin as Covid treatment withdrawn over ethical concerns". The Guardian. Archived from the original on January 16, 2022. Retrieved May 12, 2023.
93. ^ 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.
94. Omaswa F, Crisp N (2014). African Health Leaders: Making Change and Claiming the Future. OUP Oxford. p. PT158. ISBN 978-0191008412. Archived from the original on August 3, 2020. Retrieved April 6, 2020.
95. Arévalo AP, Pagotto R, Pórfido JL, Daghero H, Segovia M, Yamasaki K, et al. (March 2021). "Ivermectin reduces in vivo coronavirus infection in a mouse experimental model". Scientific Reports. 11 (1): 7132. Bibcode:2021NatSR..11.7132A. doi:10.1038/s41598-021-86679-0. PMC 8010049. PMID 33785846.
96. Kliegman RM, St Geme J (2019). Nelson Textbook of Pediatrics E-Book. Elsevier Health Sciences. p. 3575. ISBN 978-0323568883. Archived from the original on August 3, 2020. Retrieved April 6, 2020.
97. 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. Archived from the original on March 18, 2023. Retrieved July 4, 2020.
98. 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. Archived from the original on October 19, 2021. Retrieved July 4, 2020.
99. "Sklice – ivermectin lotion". DailyMed. November 9, 2017. Archived from the original on October 31, 2020. Retrieved October 28, 2020.
100. 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.
101. 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): 797–799. doi:10.1016/0035-9203(85)90121-X. PMID 3832491.
102. Udensi K (September 2012). "Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected mice". Journal of Vector Borne Diseases. 49 (3): 143–150. doi:10.4103/0972-9062.213454. PMID 23135008.
103. Kent ML, Watral V, Gaulke CA, Sharpton TJ (October 2019). "Further evaluation of the efficacy of emamectin benzoate for treating Pseudocapillaria tomentosa (Dujardin 1843) in zebrafish Danio rerio (Hamilton 1822)". Journal of Fish Diseases. 42 (10): 1351–1357. Bibcode:2019JFDis..42.1351K. doi:10.1111/jfd.13057. PMC 6744302. PMID 31309582.
104. 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.
105. 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.
106. Fontinha D, Moules I, Prudêncio M (July 2020). "Repurposing Drugs to Fight Hepatic Malaria Parasites". Molecules. 25 (15): 3409. doi:10.3390/molecules25153409. PMC 7435416. PMID 32731386.
107. ^ de Souza DK, Thomas R, Bradley J, Leyrat C, Boakye DA, Okebe J, et al. (Cochrane Infectious Diseases Group) (June 2021). "Ivermectin treatment in humans for reducing malaria transmission". The Cochrane Database of Systematic Reviews. 2021 (6): CD013117. doi:10.1002/14651858.CD013117.pub2. PMC 8240090. PMID 34184757.
108. Tizifa TA, Kabaghe AN, McCann RS, van den Berg H, Van Vugt M, Phiri KS (2018). "Prevention Efforts for Malaria". Current Tropical Medicine Reports. 5 (1): 41–50. doi:10.1007/s40475-018-0133-y. PMC 5879044. PMID 29629252.
109. Milton P, Hamley JI, Walker M, Basáñez MG (November 2020). "Moxidectin: an oral treatment for human onchocerciasis". Expert Review of Anti-Infective Therapy. 18 (11): 1067–1081. doi:10.1080/14787210.2020.1792772. hdl:10044/1/81294. PMID 32715787.
110. 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. S2CID 46921091.
111. 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.
112. Crump A (May 2017). "Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations". The Journal of Antibiotics. 70 (5): 495–505. doi:10.1038/ja.2017.11. PMID 28196978.
113. Ōmura S (August 2016). "A Splendid Gift from the Earth: The Origins and Impact of the Avermectins (Nobel Lecture)". Angewandte Chemie. 55 (35): 10190–10209. doi:10.1002/anie.201602164. PMID 27435664. Archived from the original on October 19, 2021. Retrieved April 6, 2020.
114. James WD, Elston D, Berger T, Neuhaus I (2015). Andrews' Diseases of the Skin: Clinical Dermatology. Elsevier Health Sciences. p. 439. ISBN 978-0323319690. Archived from the original on June 26, 2020. Retrieved April 6, 2020. Ivermectin treatment is emerging as a potential ancillary measure.
115. Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I (2017). Treatment of Skin Disease: Comprehensive Therapeutic Strategies. Elsevier Health Sciences. p. 89. ISBN 978-0702069130. Archived from the original on June 26, 2020. Retrieved April 6, 2020.
116. Carotti A, Marinozzi M, Custodi C, Cerra B, Pellicciari R, Gioiello A, et al. (2014). "Beyond bile acids: targeting Farnesoid X Receptor (FXR) with natural and synthetic ligands". Current Topics in Medicinal Chemistry. 14 (19): 2129–2142. doi:10.2174/1568026614666141112094058. PMID 25388537. Archived from the original on October 19, 2021. Retrieved April 6, 2020.
117. 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.
118. 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.
119. Popp M, Reis S, Schießer S, Hausinger RI, Stegemann M, Metzendorf MI, et al. (June 2022). "Ivermectin for preventing and treating COVID-19". The Cochrane Database of Systematic Reviews. 2022 (6): CD015017. doi:10.1002/14651858.CD015017.pub3. PMC 9215332. PMID 35726131.
120. Reis G, Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, et al. (May 2022). "Effect of Early Treatment with Ivermectin among Patients with Covid-19". The New England Journal of Medicine. 386 (18): 1721–1731. doi:10.1056/NEJMoa2115869. PMC 9006771. PMID 35353979.
121. Kaplan RM, Vidyashankar AN (May 2012). "An inconvenient truth: global worming and anthelmintic resistance". Veterinary Parasitology. 186 (1–2): 70–78. doi:10.1016/j.vetpar.2011.11.048. PMID 22154968.
122. Geurden T, Chartier C, Fanke J, di Regalbono AF, Traversa D, von Samson-Himmelstjerna G, et al. (December 2015). "Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe". International Journal for Parasitology: Drugs and Drug Resistance. 5 (3): 163–171. doi:10.1016/j.ijpddr.2015.08.001. PMC 4572401. PMID 26448902.
123. Peña-Espinoza M, Thamsborg SM, Denwood MJ, Drag M, Hansen TV, Jensen VF, et al. (December 2016). "Efficacy of ivermectin against gastrointestinal nematodes of cattle in Denmark evaluated by different methods for analysis of faecal egg count reduction". International Journal for Parasitology: Drugs and Drug Resistance. 6 (3): 241–250. doi:10.1016/j.ijpddr.2016.10.004. PMC 5107639. PMID 27835769.
124. Verdú JR, Cortez V, Ortiz AJ, Lumaret JP, Lobo JM, Sánchez-Piñero F (June 2020). "Biomagnification and body distribution of ivermectin in dung beetles". Scientific Reports. 10 (1): 9073. Bibcode:2020NatSR..10.9073V. doi:10.1038/s41598-020-66063-0. hdl:10481/63204. PMC 7270108. PMID 32493927.
125. Papich MG (January 1, 2016). "Ivermectin". In Papich MG (ed.). Saunders Handbook of Veterinary Drugs (Fourth ed.). W.B. Saunders. pp. 420–23. doi:10.1016/B978-0-323-24485-5.00323-5. ISBN 978-0-323-24485-5.
126. Dowling P (December 2006). "Pharmacogenetics: it's not just about ivermectin in collies". The Canadian Veterinary Journal. 47 (12): 1165–1168. PMC 1636591. PMID 17217086.
127. "MDR1 FAQs". Australian Shepherd Health & Genetics Institute, Inc. Archived from the original on December 13, 2007.
128. "Multidrug Sensitivity in Dogs". Washington State University's College of Veterinary Medicine. Archived from the original on June 23, 2015.
129. "Comfortis- spinosad tablet, chewable". DailyMed. Archived from the original on August 15, 2021. Retrieved August 14, 2021.
130. "Comfortis and ivermectin interaction Safety Warning Notification". U.S. Food and Drug Administration (FDA). Archived from the original on August 29, 2009.
131. "Acarexx". Boehringer Ingelheim. April 11, 2016. Archived from the original on October 19, 2021. Retrieved February 16, 2019.
132. Frischke H, Hunt L (April 1991). "Alberta. Suspected ivermectin toxicity in kittens". The Canadian Veterinary Journal. 32 (4): 245. PMC 1481314. PMID 17423775.
133. Klingenberg R (2007). Understanding reptile parasites: from the experts at Advanced Vivarium Systems. Irvine, Calif: Advanced Vivarium Systems. ISBN 978-1882770908.

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