Ivermectin is an avermectin and a fermentation product of Streptomyces avermitilis (also see Macrocyclic Lactones Macrocyclic Lactones The macrocyclic lactones (avermectins and milbemycins) are products or chemical derivatives of soil microorganisms belonging to the genus Streptomyces. The avermectins in commercial use are... read more ). It acts as a GABA agonist, causing paralysis in susceptible arthropods and nematodes. It is used in small animals for treatment of Sarcoptes scabiei, Otodectes cynotis, Cheyletiella blakei, C yasguri, and Demodex canis; in cattle for psoroptic mange, lice, and Hypoderma larvae; in horses for equine filarial dermatitis from Onchocerca cervicalis; and in swine for Sarcoptes scabiei.
In small animals, all use for skin conditions is extra-label in the USA. For Demodex, the dosage is 0.3–0.6 mg/kg/day, PO, until two negative skin scrapings 1 mo apart. For Sarcoptes, Otodectes, and Cheyletiella, the dosage is 0.3 mg/kg, PO, repeated in 2 wk. In cattle, 0.2 mg/kg is given as a single SC injection for Psoroptes and lice. In horses, 0.2 mg/kg, PO, kills microfilariae but not adult Onchocerca cervicalis, so relapse may be noted within 2 mo of treatment. In swine, the dosage is 0.3 mg/kg, SC, repeated in 2 wk, or 0.1–0.2 mg/kg in feed for 7 days.
In mammals, GABA is found only in the CNS and does not readily cross the blood-brain barrier. At least 10 times the normal dose of ivermectin is needed for toxic reactions. Ataxia, depression, and visual impairment develop in horses given 2 mg/kg, PO. In cattle, 4 mg/kg by drench or 8 mg/kg, SC, leads to listlessness and ataxia; 30 mg/kg induces ataxia in swine.
Some dog breeds (Collies, Shetland Sheepdogs, Old English Sheepdogs, Australian Collies, and their crosses) have an abnormality in the blood-brain barrier associated with a mutation of the multiple drug resistance gene MDR1, which allows increased ivermectin into the CNS and results in toxicity. Dogs that are homozygous for the mutation produce a severely truncated P-glycoprotein (<10% of the normal amino acid sequence) and will develop ivermectin toxicity at any of the dosages used to treat demodicosis. The critical point seems to be 120–150 mcg/kg, at which transient, nonfatal clinical signs (mydriasis, ataxia, tremors) are seen. At higher dosages, collapse, coma, and respiratory collapse may develop. Similar idiosyncratic reactions may develop in any breed, so a gradually increasing dose (daily progression of 50, 100, 150, 200, then 300 mcg/kg) should be given to identify susceptible individuals. Administration should be stopped if any adverse effects are seen. One cat treated with 4 mg of the oral paste (~70 mcg/kg) showed ataxia, blindness, tremors, and mydriasis, with retinal atrophy in one eye 10 hr later.
Milbemycin is derived from fermentation products of Streptomyces hygroscopicus and, like ivermectin, acts as a GABA agonist but with a wider spectrum of activity against intestinal parasites. It has been used extra-label in dogs to treat nasal mites, scabies, and generalized demodicosis. No adverse effects have been seen in ivermectin-sensitive breeds. The dosage in dogs is 1–2 mg/kg every 7 days for 3–5 treatments for nasal mites and scabies and 1–2 mg/kg/day for Demodex.
Moxidectin belongs to the milbemycin class of compounds. It is registered for heartworm control (Dirofilaria immitis) but has also been used extra-label for treatment of Otodectes and demodicosis in dogs. In cattle, it is used to treat lice (Linognathus vituli, Solenopotes capillatus, Bovicola bovis), mites (Psoroptes, Chorioptes bovis), ticks (Boophilus microplus), and fly warbles and grubs (Hypoderma bovis, Hypoderma lineatum). In sheep, it is used for Psorobia ovis infestation. The dosage is 0.2–0.4 mg/kg/day, PO, in dogs and 0.2 mg/kg in cattle and sheep.
This semisynthetic macrocyclic lactone is applied topically but acts systemically. It is effective against Ctenocephalides spp (both adults and larvae), Sarcoptes scabiei, Otodectes cynotis, and Dermacentor variabilis. The dosage in dogs and cats is 6 mg/kg, applied topically.
Lufenuron is an insect growth regulator that inhibits the synthesis of chitin, a critical component of insect exoskeletons. It is taken up by adult fleas while feeding. While it has no effect on adult fleas, it prevents development of the intermediate stages of the flea life cycle (ie, eggs, larvae, pupae). It is effective against Ctenocephalides spp in dogs and cats at a dosage of 10 mg/kg, PO, once a month. Chitin is also a component in the fungal cell wall of dermatophytes. An initial study showed efficacy of lufenuron in treating small animal dermatophytosis; however, additional studies have failed to show efficacy.
Nitenpyram inhibits the nicotinic acetylcholine receptor. It is used to treat Ctenocephalides spp in dogs and cats at a dosage of 1 mg/kg, PO. Nitenpyram has a short half-life and kills fleas on the animal within 30 min of administration. It is toxic to fleas for only 24–48 hr and is normally used in combination with an insect growth regulator to provide continuous flea control.
Spinosad stimulates the nicotinic acetycholine receptor, which causes activation of motor neurons and results in involuntary muscle contractions and tremors, leading to paralysis and death of the insect. It is used to treat Ctenophalides spp in dogs at a dosage of 31–70 mg/kg monthly and in cats at a dosage of 50–90 mg/kg monthly. It may trigger severe signs of ivermectin toxicity if administered concurrently with extra-label, high-dose ivermectin.
Indoxacarb blocks sodium channels in the insect to cause paralysis and death. It is effective against Ctenophalides spp, both adults and larvae, and is applied as a spot-on topically, once a month.
Cythioate is an organophosphate that kills via anticholinesterase activity. It is indicated for Ctenocephalides spp infestations at a dosage of 3 mg/kg, PO, twice weekly (dogs) or 1.5 mg/kg, PO, twice weekly (cats). Although effective blood levels are maintained for <12 hr, serum cholinesterase activity may be decreased for >1 mo after dosing.
Sodium stiboglucoante is used for treatment of cutaneous leishmaniasis, either as a sole therapy or in combination with allopurinol, paromomycin, or pentamidine. The exact mode of action is unknown, but it is believed to interfere with energy metabolism in Leishmania amastigotes. Dosage in dogs is 30–50 mg/kg/day, IV or SC, for 3–4 wk. If adverse effects occur (musculoskeletal pain, increase in liver transaminases, pancreatitis, myocardial injury, hemolytic anemia, leukopenia, renal dysfunction), the dose may be administered every other day for longer periods. Note that IV administration should be over 5 min to minimize cardiotoxicity.