Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) is a broad-spectrum antiparasiticdrug in the avermectin family. It is sold under brand namesHeartgard,Sklice, and Stromectol in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, 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.
Ivermectin, under the brand name Mectizan, 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. Currently, large amounts of ivermectin are donated by Merck to fight river blindness in countries unable to afford the drug. 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:
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) 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.
For dogs, the insecticide spinosad may have the effect of increasing the potency of ivermectin.
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.
Ivermectin is contraindicated in children under the age of five, or those who weigh less than 15 kg (33 lb); and those who are breastfeeding, and have a hepatic or renal disease.
The discovery of the avermectin family of compounds, from which ivermectin is chemically derived, was made by a team of scientists at Merck Institute for Therapeutic Research. A large international program of development resulted in the introduction of ivermectin as a commercial antiparasitic agent in 1981.
Ivermectin is also used in veterinary medicine. 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.
^Borst P, Schinkel AH (June 1996). "What have we learnt thus far from mice with disrupted P-glycoprotein genes?". European Journal of Cancer32 (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 Research100 (1): 93–102. doi:10.1007/s00436-006-0240-x. PMID16821034.
^Huukelbach J, Winter B, Wilcke T, "et al." (August 2004). "Tratmient masivo selectivo con ivermectina contra las helmintiasis intestinales y parasitos cutáneas en una población gravemente afectada". Bull World Health Organ82 (7): 563–571. doi:10.1590/S0042-96862004000800005.
^W. C. CAMPBELL; R. W. BURG, , M. H. FISHER, and , R. A. DYBAS (June 26, 1984). "1". The Discovery of Ivermectin and Other Avermectins. American Chemical Society. pp. 5–20. ISBN9780841210837.Cite uses deprecated parameters (help)
^"MDR1 FAQs", Australian Shepherd Health & Genetics Institute, Inc.