Moxidectin

Moxidectin was approved for onchocerciasis (river-blindness) in 2018 for people over the age of 11 in the United States based on two studies.{{cite journal | vauthors = Awadzi K, Opoku NO, Attah SK, Lazdins-Helds J, Kuesel AC | title = A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 6 | pages = e2953 | date = June 2014 | pmid = 24968000 | pmc = 4072596 | doi = 10.1371/journal.pntd.0002953 | doi-access = free }} There is a need for additional trials, with long-term follow-up, to assess whether moxidectin is safe and effective for treatment of nematode infection in children and women of childbearing potential.{{cite journal | vauthors = Maheu-Giroux M, Joseph SA | title = Moxidectin for deworming: from trials to implementation | journal = The Lancet. Infectious Diseases | volume = 18 | issue = 8 | pages = 817–819 | date = August 2018 | pmid = 29858152 | doi = 10.1016/S1473-3099(18)30270-6 | s2cid = 46921091 }} Moxidectin is predicted to be helpful to achieve elimination goals of this disease.{{cite journal | vauthors = Turner HC, Walker M, Attah SK, Opoku NO, Awadzi K, Kuesel AC, Basáñez MG | title = The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data | journal = Parasites & Vectors | volume = 8 | pages = 167 | date = March 2015 | pmid = 25889256 | pmc = 4381491 | doi = 10.1186/s13071-015-0779-4 | doi-access = free }}

• Dogs: Prevention of heartworm. In combination with imidacloprid to treat sarcoptic mange.
• Horses: Treatment of parasites including Strongylus vulgaris, and stomach bots such as Gasterophilus intestinalis.{{cite book| vauthors = Papich MG |title=Saunders handbook of veterinary drugs small and large animal|date=2011|publisher=Elsevier/Saunders|location=Philadelphia, PA|isbn=9781437701920|pages=525–526|edition=3rd|chapter=Moxidectin}}
• Cattle: Treatment of parasites such as the gastrointestinal nematode Ostertagia ostertagi, and the lungworm Dictyocaulus viviparus.
• Sheep: Treatment of the nematodes Teladorsagia circumcincta and Haemonchus contortus.{{cite book| vauthors = Sargison N |title=Sheep flock health a planned approach|date=2008|publisher=Blackwell Publishing|location=Oxford|isbn=9781444302608|pages=180–181|chapter=Moxidectin}}

Nematodes can develop cross-resistance between moxidectin and other similar parasiticides, such as ivermectin, doramectin and abamectin.{{cite book| vauthors = Rugg D, Buckingham SD, Sattelle DB, Jansson RK | veditors = Gilbert GI, Gill SS |title=Insect pharmacology channels, receptors, toxins and enzymes|date=2010|publisher=Academic Press|location=London|isbn=9780123814487|chapter=The insecticidal macrocyclic lactones}} The ways in which the parasites evolve resistance to this drug include mutations in glutamate-gated chloride channel genes, GABA-R genes,{{cite journal | vauthors = Wolstenholme AJ, Fairweather I, Prichard R, von Samson-Himmelstjerna G, Sangster NC | title = Drug resistance in veterinary helminths | journal = Trends in Parasitology | volume = 20 | issue = 10 | pages = 469–476 | date = October 2004 | pmid = 15363440 | doi = 10.1016/j.pt.2004.07.010 }} or increased expression of p-glycoprotein, which is a transmembrane drug efflux pump.{{cite journal | vauthors = Blackhall WJ, Prichard RK, Beech RN | title = P-glycoprotein selection in strains of Haemonchus contortus resistant to benzimidazoles | journal = Veterinary Parasitology | volume = 152 | issue = 1–2 | pages = 101–107 | date = March 2008 | pmid = 18241994 | doi = 10.1016/j.vetpar.2007.12.001 }} Allele frequency changes corresponding to resistance to moxidectin and/or other macrocyclic lactone-class drugs have been observed in the glutamate-gated chloride channel α-subunit gene of Haemonchus contortus and Cooperia oncophora, as well as in the H. contortus genes coding for p-glycoprotein and the GABA-R gene.

Moxidectin is being evaluated as a treatment to eradicate scabies in humans, especially when resistant to other treatments.{{cite journal | vauthors = Mounsey KE, Bernigaud C, Chosidow O, McCarthy JS | title = Prospects for Moxidectin as a New Oral Treatment for Human Scabies | journal = PLOS Neglected Tropical Diseases | volume = 10 | issue = 3 | pages = e0004389 | date = March 2016 | pmid = 26985995 | pmc = 4795782 | doi = 10.1371/journal.pntd.0004389 | doi-access = free }}

Studies of moxidectin show the side effects vary by animal and may be affected by the product's formulation, application method and dosage.{{citation needed|date=December 2022}}. It is however regarded as relatively safe.{{cite journal | vauthors = Schraven AL, Stannard HJ, Old JM | title = A systematic review of moxidectin as a treatment for parasitic infections in mammalian species. | journal = Parasitology Research | volume = 120 | pages = 1167–1181 | date = 2021 | issue = 4 | doi = 10.1007/s00436-021-07092-0 | pmid = 33615411 }}

An overdose of moxidectin enhances the effect of gamma-aminobutyric acid (GABA) in the central nervous system. In horses, overdose may lead to depression, drooping of the lower lip, tremor, lack of coordination when moving (ataxia), decreased rate of breathing (respiratory rate), stupor and coma.{{cite book| vauthors = Dowling PM | veditors = Wilson DA |title=Clinical veterinary advisor: The horse|date=2012|publisher=Elsevier Saunders|location=St. Louis, MO|isbn=9781437714494|pages=307–308|chapter=Ivermectin and moxidectin toxicosis}}

If a dog licks moxidectin from the skin which was applied as a "spot-on" (topical) treatment, this has the same effect as an overdose, and may cause vomiting, salivation and neurological signs such as ataxia, tremor, and nystagmus. Some Collie dogs can tolerate moxidectin, but other individuals are sensitive and upon ingestion, experience vomiting, salivation or transient neurological signs.

Moxidectin is very lipophilic, which causes it to have a high volume of distribution.{{cite book| vauthors = Lanusse CE, Lifschitz AL, Imperiale FA | veditors = Riviere JE, Papich MG |title=Veterinary Pharmacology and Therapeutics|date=2013|publisher=John Wiley & Sons|isbn=978-1118685907|edition=9th|page=1126|chapter=Chapter 42: Macrocyclic lactones: Endectocide compounds}} Moxidectin concentrates in the animal's adipose tissue, from where it is released for up to two months following administration.

In goats, the oral bioavailability of moxidectin is 2.7 times lower, and the half-life is 1.8 times shorter than in sheep.{{cite journal | vauthors = Baynes RE, Payne M, Martin-Jimenez T, Abdullah AR, Anderson KL, Webb AI, Craigmill A, Riviere JE | display-authors = 6 | title = Extralabel use of ivermectin and moxidectin in food animals | journal = Journal of the American Veterinary Medical Association | volume = 217 | issue = 5 | pages = 668–671 | date = September 2000 | pmid = 10976297 | doi = 10.2460/javma.2000.217.668 | doi-access = free }}

Moxidectin, a macrocyclic lactone of the milbemycin class,{{cite book| vauthors = Patel A, Forsythe P |title=Small animal dermatology|url=https://archive.org/details/smallanimalderma0000pate|url-access=registration|date=2008|publisher=Elsevier/Saunders|location=Edinburgh|isbn=9780702028700|page=[https://archive.org/details/smallanimalderma0000pate/page/26 26]}} is a semisynthetic derivative of nemadectin, which is a fermentation product of the bacterium Streptomyces cyanogriseus subsp. noncyanogenus.{{cite journal | vauthors = Lumaret JP, Errouissi F, Floate K, Römbke J, Wardhaugh K | title = A review on the toxicity and non-target effects of macrocyclic lactones in terrestrial and aquatic environments | journal = Current Pharmaceutical Biotechnology | volume = 13 | issue = 6 | pages = 1004–1060 | date = May 2012 | pmid = 22039795 | pmc = 3409360 | doi = 10.2174/138920112800399257 }}

In the late 1980s, an American Cyanamid Company agronomist discovered the Streptomyces bacteria from which moxidectin is derived in a soil sample from Australia.

Two companies filed patents for moxidectin: Glaxo Group and the American Cyanamid Company; in 1988, all patents were transferred to American Cyanamid. In 1990, the first moxidectin product was sold in Argentina.{{cite book| vauthors = Awasthi A, Razzak M, Al-Kassas R, Harvey J, Garg S | veditors = Brittain H |title=Profiles of drug substances, excipients and related methodology: Volume 38|date=2013|publisher=Academic Press|location=Amsterdam|isbn=9780124078284|pages=315–366|chapter=Chapter 7: Analytical profile of moxidectin}}

For human use, moxidectin was approved by the United States Food and Drug Administration in June 2018 for the treatment of onchocerciasis in adults and adolescents aged 12 and older. This is the first human approval worldwide. The license holder is the nonprofit biopharmaceutical company Medicines Development for Global Health.{{cite web | title = MOXIDECTIN tablet | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6eb02ae9-9065-176f-e053-2991aa0ac891 | work = Dailymed | publisher = U.S. National Library of Medicine }}

{{reflist}}

{{Endectocides|state=collapsed}}

{{Portal bar | Medicine}}

Category:Anthelmintics

Category:Veterinary drugs

Category:Orphan drugs

Category:Ketoxime ethers