|Systematic (IUPAC) name|
22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
|Biological half-life||18 hours|
|Excretion||Feces; <1% urine|
|ATC code||D11 P02 QP54 QS02|
|PDB ligand ID||IVM (, )|
14 (22,23-dihydroavermectin B1a)
14 (22,23-dihydroavermectin B1b)
|Molecular mass||875.10 g/mol|
|(what is this?)|
Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) is a broad-spectrum antiparasitic drug in the avermectin family. It is taken internally or used topically, depending on the treated condition.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Ivermectin is a broad-spectrum antiparasitic agent, traditionally against parasitic worms. It is mainly used in humans in the treatment of onchocerciasis (river blindness), but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis, filariasis and enterobiasis), and some epidermal parasitic skin diseases, including scabies.
Ivermectin is currently being used to help eliminate river blindness (onchocerciasis) in the Americas, and to stop transmission of lymphatic filariasis and onchocerciasis around the world in programs sponsored by the Carter Center using ivermectin donated by Merck. The disease is endemic in 30 African countries, six Latin American countries, and Yemen, according to studies conducted by the World Health Organization. The drug rapidly kills microfilariae, but not the adult worms. A single oral dose of ivermectin, taken annually for the 10- to 15-year lifespan of the adult worms, is all that is needed to protect the individual from onchocerciasis.
More recent evidence supports its use against parasitic arthropods and insects:
- Mites such as scabies: It is usually limited to cases that prove to be resistant to topical treatments or that present in an advanced state (such as Norwegian scabies).
- Lice: Ivermectin lotion (0.5%) is FDA-approved for patients six months of age and older. After a single, 10-minute application of this formulation on dry hair, 78% of subjects were found to be free of lice after two weeks. This level of effectiveness is equivalent to other pediculicide treatments requiring two applications.
- Bed bugs: Early research shows that the drug kills bed bugs when taken by humans at normal doses. The drug enters the human bloodstream and if the bedbugs bite during that time, they will die in a few days.
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.
Dogs with defects in the P-glycoprotein gene (MDR1), often collie-like herding dogs, can be severely poisoned by ivermectin.
Since drugs that inhibit CYP3A4 enzymes 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, and glucocorticoids such as dexamethasone, lidocaine, and the benzodiazepines.
Ivermectin and other avermectins (insecticides most frequently used in home-use ant baits) are macrocyclic lactones derived from the bacterium Streptomyces avermitilis. Ivermectin kills by interfering with nervous system and muscle function, in particular by enhancing inhibitory neurotransmission.
The drug binds and activates glutamate-gated chloride channels (GluCls). GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channels present in neurons and myocytes.
Ivermectin can be given either by mouth or injection. It does not readily cross the blood–brain barrier of mammals due to the presence of P-glycoprotein, (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 hr after administration). In contrast to mammals, ivermectin can cross the blood–brain barrier in tortoises, often with fatal consequences.
Field studies have demonstrated the dung of animals treated with ivermectin supports a significantly reduced diversity of invertebrates, and the dung persists longer.
The discovery of the avermectin family of compounds, from which ivermectin is chemically derived, was made by Satoshi Ōmura of Kitasato University, Tokyo and William C. Campbell of the Merck Institute for Therapeutic research. Ōmura identified avermectin from the bacterium Streptomyces avermitilis. Campbell purified avermectin from cultures obtained from Ōmura and led efforts leading to the discovery of ivermectin, a derivative of greater potency and lower toxicity. Ivermectin was introduced in 1981. 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".
It is sold under 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. While in development, it was assigned the code MK-933 by Merck.
In veterinary medicine ivermectin is used against many intestinal worms (but not tapeworms), most mites, and some lice. Despite this, it is not effective for eliminating ticks, flies, flukes, or fleas. It is effective against larval heartworms, but not against adult heartworms, though it may shorten their lives. The dose of the medicine must be very accurately measured as it is very toxic in over-dosage. It is sometimes administered in combination with other medications to treat a broad spectrum of animal parasites. Some dog breeds (especially the Rough Collie, the Smooth Collie, the Shetland Sheepdog, and the Australian Shepherd), though, have a high incidence of a certain mutation within the MDR1 gene (coding for P-glycoprotein); affected animals are particularly sensitive to the toxic effects of ivermectin. Clinical evidence suggests kittens are susceptible to ivermectin toxicity. A 0.01% ivermectin topical preparation for treating ear mites in cats (Acarexx) is available.
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.
Notes and references
- "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- The Carter Center. "River Blindness (Onchocerciasis) Program". Retrieved 2008-07-17..
- The Carter Center. "Lymphatic Filariasis Elimination Program". Retrieved 2008-07-17..
- WHO. "African Programme for Onchocerciasis Control". Retrieved 2009-11-12..
- United Front Against Riverblindness. "Onchocerciasis or Riverblindness"..
- United Front Against Riverblindness. "Control of Riverblindness"..
- Galderma Receives FDA Approval of Soolantra (Ivermectin) Cream for Rosacea"
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- Brooks PA, Grace RF (August 2002). "Ivermectin is better than benzyl benzoate for childhood scabies in developing countries". J Paediatr Child Health 38 (4): 401–4. doi:10.1046/j.1440-1754.2002.00015.x. PMID 12174005.
- Victoria J, Trujillo R (2001). "Topical ivermectin: a new successful treatment for scabies". Pediatr Dermatol 18 (1): 63–5. doi:10.1046/j.1525-1470.2001.018001063.x. PMID 11207977.
- Strong M, Johnstone PW (2007). Strong, Mark, ed. "Interventions for treating scabies". Cochrane Database of Systematic Reviews (Online) (3): CD000320. doi:10.1002/14651858.CD000320.pub2. PMID 17636630.
- 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.
- Strycharz JP, Yoon KS, Clark JM (January 2008). "A new ivermectin formulation topically kills permethrin-resistant human head lice (Anoplura: Pediculidae)". Journal of Medical Entomology 45 (1): 75–81. doi:10.1603/0022-2585(2008)45[75:ANIFTK]2.0.CO;2. ISSN 0022-2585. PMID 18283945.
- "Sklice lotion".
- David M. Pariser, M.D., Terri Lynn Meinking, Ph.D., Margie Bell, M.S., and William G. Ryan, B.V.Sc. (November 1, 2012). "Topical 0.5% Ivermectin Lotion for Treatment of Head Lice". New England Journal of Medicine 367: 1687–1693. doi:10.1056/NEJMoa1200107.
- Study shows ivermectin ending lice problem in one treatment, Los Angeles Times, Nov 5, 2012
- DONALD G. MCNEIL JR. (2012-12-31). "Pill Could Join Arsenal Against Bedbugs". The New York Times. Retrieved 2013-04-05.
- 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.
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- Goodman and Gilman's Pharmacological Basis of Therapeutics, 11th edition, pages 122, 1084-1087.
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- Borst P, Schinkel AH (June 1996). "What have we learnt thus far from mice with disrupted P-glycoprotein genes?". European Journal of Cancer 32 (6): 985–990. doi:10.1016/0959-8049(96)00063-9.
- Iglesias LE, Saumell CA, Fernández AS, et al. (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.
- Fisher MH, Mrozik H (1992). "The chemistry and pharmacology of avermectins". Annu. Rev. Pharmacol. Toxicol. 32: 537–53. doi:10.1146/annurev.pa.32.040192.002541. PMID 1605577.
- W. C. CAMPBELL; R. W. BURG, , M. H. FISHER, and , R. A. DYBAS (June 26, 1984). "The Discovery of Ivermectin and Other Avermectins". American Chemical Society. pp. 5–20. ISBN 9780841210837.
- "The Nobel Prize in Physiology or Medicine 2015" (PDF). Nobel Foundation. Retrieved 7 October 2015.
- "SKLICE- ivermectin lotion (NDC Code(s): 49281-183-71)". DailyMed. February 2012. Retrieved 2015-09-09.
- "STROMECTOL- ivermectin tablet (NDC Code(s): 0006-0032-20)". DailyMed. May 2010. Retrieved 2015-09-09.
- Adhikari, Santosh (2014-05-27). "ALIVE PHARMACEUTICAL (P) LTD.: Iver-DT". ALIVE PHARMACEUTICAL (P) LTD. Retrieved 2015-10-07.
- Pampiglione S, Majori G, Petrangeli G, Romi R (1985). "Avermectins, MK-933 and MK-936, for mosquito control". Trans R Soc Trop Med Hyg 79 (6): 797–9. doi:10.1016/0035-9203(85)90121-X. PMID 3832491.
- "MDR1 FAQs", Australian Shepherd Health & Genetics Institute, Inc.
- "Multidrug Sensitivity in Dogs", Washington State University's College of Veterinary Medicine
- Frischke H, Hunt L (April 1991). "Suspected ivermectin toxicity". Canadian Veterinary Journal 32 (4): 245. PMC 1481314. PMID 17423775.
- The Carter Center River Blindness (Onchocerciasis) Control Program
- Mectizan Donation Program
- American NGDO Treating River Blindness
- MERCK. 25 Years: The MECTIZAN® Donation Program
- Trinity College Dublin. Prof William Campbell - The Story of Ivermectin
- "IVERMECTIN- ivermectin tablet (NDC Code(s): 42799-806-01)". DailyMed. November 2014. Retrieved 2015-09-09.
- "ivermectin (Rx) Stromectol". Medscape. WebMD. Retrieved 2015-11-01.