dogs and cats the half life of selamectin 11 and 8 days

Issues involving parasite prevention and treatment. Questions, answers, theories, and evidence.
Do pets really need medication every month for worms, fleas and ticks?

dogs and cats the half life of selamectin 11 and 8 days

Postby malernee » Wed Jul 26, 2006 11:22 am

Israel Veterinary Medical Association

Vol. 58 (2-3) 2003


E. Pipano.

The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem. P.O. Box 12, 76100 Rehovot, Israel.

Efficacy against fleas Efficacy against mites Efficacy against ticks efficacy against nematodes Safety of selamectin

Ecto-and- endoparasites cause heavy burden, clinical disease and death in dogs and cats. In addition to the damage they cause as pests, ectoparasites act as vectors of veterinary and medical pathogens of importance while endoparasites frequently cause zoonoses.

The last two decades have witnessed important changes in the provision of veterinary services to pet animals. Animal owners have increasing expectations of what can be achieved in terms of treatment and prevention of disease conditions and tremendous expansion in veterinary pharmaceutical products has resulted from the great effort to satisfy these expectations.

The list (published in 2001) of pesticides licensed by the Israeli Veterinary Services, for treatment of pet animals comprises 110 compounds based mainly on acetylcholinesterase inhibiting organophosphors and carbamates, synthetic pyrethroids, natural pyrethrum, insect growth regulators, phenylpyrasoles, nitromethylenes, amitraz, and natural etheric oils. Chlorinated hydrocarbons have been banned for use with pet animals and livestock or in their surroundings.

Avermectins and milbemicins emerged as compounds having a high efficacy against ectoparasites and effective in simultaneously killing nematode worms in the host. As a result ivermectin, doramectin and milbemicin became well accepted for the treatment of parasitic invasions in livestock. However, avermectin and milbemycin compounds do not possess a therapeutic ratio (chemotherapeutic index) in dogs and cats, adequate to achieve efficacious treatment against ecto- and endopasites in these animals, and at the same time having a high safety profile.

The recently developed endoctocide, selamectin, combines complete safety with high anti-ectoparasitic and anti-helmintic activity in dogs and cats. The following describes the characteristics of this product registered, in 2002 in Israel, as a prescribed drug.

Selamectin is a semi-synthetic modification of doramectin produced from a bio-engineered new strain of Streptomyces avermitilis (1). Similar to other macrolitic lactones, it has a mechanism of action that may involve more than one site (2). Selamectin causes neuromuscular paralysis in target parasites by increasing permeability in neuronal chloride channels primarily through glutamate-gaited channels. A possible target of GABA g-amino-butiric acid) - modulated chloride channels is also suggested. Once selamectin is bound to the receptor the chloride channels remains open and chloride ions flow into the nerve cell. At the ultrastructural level, damage restricted to nerves and muscles are seen one hour after feeding fleas on selamectin-treated animals. After 24 h an overall cell lysis, including also epidermal, intestinal or sexual cell system is observed (3). Because chloride channels in mammals are less accessible and less sensitive to avermectins than those in arthropod parasites and nematodes, this class of compounds possesses a wide therapeutic safety margin.

Bioavailability after dermal application in cats and dogs is 74% and 4.4%, respectively. Grooming, resulting in oral ingestion of topically applied selamectin, may account for its high bioavailability in cats. Selamectin is absorbed rapidly after topical application and achieves a peak plasma concentration three days after treatment. Following topical application, selamectin is absorbed into the bloodstream and some of the compound is excreted into the intestinal tract. Substantial amounts of circulating selamectin are deposited in the sebaceous glands, which then act as reservoirs to provide persistent activity against various ectoparasitic infections. (2). In both dogs and cats the half life of selamectin (11 and 8 days respectively) following topical application was substantially longer than the half life following intravenous administration, indicating that a continuous and prolonged absorption occurs from an extravascular site. Autoradiography studies of biopsy sites along the dorsal, lateral and ventral thorax and abdomen revealed that selamectin was present at all sites. In a microscopic evaluation of biopsy sites, selamectin was identified in the sebaceous glands, hair follicles, and basal layers of the epithelium. Following topical application, selamectin persist for extend periods at concentrations that are effective against both internal and external parasites (1) and the compound is taken up by ectoparasites mainly during the blood meal (3).

Introduction Efficacy against mites Efficacy against ticks efficacy against nematodes Safety of selamectin

Efficacy against fleas
Fleas are one of the main target pests for which selamectin is indicated. The life cycle of the cat flea (Ctenocephalides felis felis) has been researched extensively and under common environmental conditions is completed in 3-5weeks (4). Once attached to a host, newly emerged adult fleas begin feeding within a few minutes. Fleas mate after feeding and egg production begins within 24-48 h of the first blood meal. Eggs are laid on the host, but fall out of the hairy coat (pellage), with approximately 70 % being dislodged within 8 h, and usually accumulate in areas where pets sleep or rest (4). Hatching occurs in 1-6 days and larvae develop in habitats where moderate temperatures and high relative humidity occur. The newly hatched larvae are free- living, feeding on adult flea fecal blood and on organic debris and tend to move down (because of positive geotaxis and negative phototaxis) between carpet fibres, organic materials or in the soil. The larva produces a silk cocoon inside which a pupa develops and the later molts to the adult stage. The fully developed adult stage can survive in the cocoon up to five months, and during this time it is extremely difficult to kill the flea with insecticides because they do not penetrate into the base of the carpet or the debris, rather than being due to any protective effect of the cocoon (5). Only a very small portion ( about 5%) of the flea population lives and feeds on animals , the remaining portion (95%) comprising eggs , larvae and pupae are spread around the indoor habitat (6), while not all insecticides are efficacious on the preimaginal stages.

The cat flea, C. felis felis, is widespread in Israel and although mainly associated with the cat this arthropod has a low host specificity and can feed on a large range of hosts including humans. Fleas have a direct effect on the host and produce allergic conditions and anemia. Allergic dermatitis is a hypersensitive state produced by the inoculation of saliva during feeding and is characterized by intense pruritus, resulting in licking, chewing and scratching. The allergic response is characterized by an immediate (10-15 min.) and delayed response (24-48 h.) following repeated exposure to flea bites (7). Since fleas are hematophagous insects they produce iron deficiency anemia particularly in young animals while heavy infestations can lead to death of the host (8,9). Fleas are vectors of Rickettsiae (murine typhus), bacteria (Yersinia), nematodes (Dipetalonema) and cestodes (Dipyllidium and Hymenolepis). Dipylidium caninum is very common among dogs in Israel and is often found in cats. The eggs of this cestode are eaten by the flea larva and an oncosphere emerges from each egg in the intestine of the larval flea and remains in the insect tissues until the latter develops into an adult flea where it transforms to cysticercoid. Dogs and cats infect themselves by eating infected fleas. Dogs and cats chew fleas when grooming and set free cysticercoid on their coat, around the mouth and on their tongue. Humans, especially children, may become infected accidentally by swallowing cysticercoids which develop in their intestines to a medium sized (25-40 cm.) tapeworm, and motile proglottids, the size of a rice grain, are passed in the stool.

Studies for controlling C.felis were conducted to evaluate: 1) adulticidal efficacy (killing adult fleas); 2) adulticidal efficacy following bathing of pets ; 3) ovicidal and larvicidal efficacy (resulting in prevention of flea infestation) and 4) effect of “debris” (dander, hair, scales and flea feces) from animals treated with selamectin on the viability of flea eggs, larvae and adults (1).

Selamectin provided long-term efficacy against fleas for a period of at least 28 days after topical application (10). Dosages of 3,6,or 9 mg/kg were applied to a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 (50 female and 50 male) viable C. felis on days 4,11,18, and 27 after the application of selamectin. The inert formulation ingredients (vehicle) was used as the control. Seventy-two hours after each infestation (days 7,14, 21 and 30), a comb count to determine the number of viable fleas present on each animal was performed. Up to day 21 the three dosages were so highly effective that it was not possible to discriminate among them. On day 30, the 6 and 9 mg dosages killed almost all fleas and were not different, which indicated that the appropriate dosage of selamectin against adult fleas on dogs and cats for a period of at least 27-30 days was 6 mg/kg (11).

The efficacy of 6 mg/kg dose was evaluated in eight controlled studies with dogs and cats against C. felis and C.canis. Groups of 8-12 dogs or cats were allocated randomly for each study. In dogs, a 99.2% and 91.8% efficacy was obtained against C. felis and C. canis respectively, at the day 30 count. Groups of 12 dogs that received a single topical dose of 6 mg/kg selamectin were immersed in water 2 h post application or bathed with shampoo at 2, 6, or 24 h post application of the drug and before infestation with C. felis. The reduction of fleas on day 30 after the application of selamectin ranged from 99.7% to 100%. Similar experiments with C. felis on cats showed 98.8% of reduction for unbathed cats, and 97.1 % to 99.4 % for bathed cats immersed in water after application of selamectin (12).

The speed of kill efficacy of selamectin against adult fleas (adulticidal effect) was evaluated with 44 dogs and 44 cats including control animals. Each animal was infested with 100 unfed viable adult C. felis and flea comb counts were performed every 12 hours for 48 h (a total of 4 counts) after treatment application. The percentage of reduction for cats was 98.9 % after 24 h and for dogs 99.8 % after 36 h. Both host species were completely free of fleas 48 h after application of selamectin (13).

For egg hatch and larval development studies dogs and cats were housed in cages designed for the collection of flea eggs. Each animal was experimentally infested with 600 unfed viable adult C. felis on the day of application of selamectin and on days 4,11,18, and 27 after the application. Flea eggs were collected 72 h after each infestation over a period of 3 h after which any remaining eggs or fleas were removed by combing. Usually adult fleas begin feeding a few minutes after infesting a new host, and mating females begin to produce eggs 24-48 h following their first blood meal. It follows that selamectin with an about 98% adulticidal efficacy 24-36 h after application, may provide only a short period over which flea eggs can be produced and shed into the environment. In fact an approximate 98% reduction in eggs collected from flea-infested dogs treated with selamectin was observed. A reduction of 92.2 % and 95.6 % reduction in hatched eggs and larvae occurred in fleas from selamectin-treated cats (13).

At the same time that adult female fleas lay eggs, they produce copious amount of feces containing a high proportion of virtually undigested blood on which larvae can feed. Debris, including flea feces, falling from selamectin-treated dogs was also shown to have high ovicidal and larvicidal activity because of their content of active selamectin, further reducing the possibility of any flea eggs or larvae already in the environment of completing their life cycle. Most debris and flea eggs tend to fall from animals where they stay longer, such as favorite resting places, both indoor and outside. Therefore, control via exposure to debris is targeted at areas more likely to have high pre-adult flea populations (13). The efficacy of selamectin in treatment and prevention of C. felis was evaluated in a simulated home environment (5). Cats were housed in carpeted rooms and dogs were housed in accommodation with raised, carpeted sleeping areas. Each of the 48 cats and 44 dogs allocated for the experiment was infested with 100 fleas, 28 and 21 days before treatment with selamectin in order to establish an environment of flea infestation. Selamectin was applicated to the animals in the medicated groups three times at 30 days apart and six comb counts were performed every 15 days starting from day 14 after the first treatment. By day 90 of the experiment the mean number of fleas for each dog was 366.9 in the controls versus 0.9 in the treated (99.8 % reduction) and for each cat, 435.7 versus 3.0 (99.3% reduction). In another environmental exposure experiment dogs and cats were infested one and 7 days after treatment, a second treatment being administered 30 days later. The percentage of reduction of flea infestation was 99.8% for dogs and 100% for cats (5). In a third study (14), dogs and cats were given five treatments at 30 days intervals and infested with fleas 28 and 21 days before treatment and then at weekly intervals. In the first treatment against the pre-established infestation selamectin achieved over 97 % reduction and an efficacy of 99.9% was maintained for the duration of the study. In comparative studies selamectin was as effective as fipronil in treating cats and as effective as fipronil and imidacloprid in treating dogs housed for three months in a flea-infested environment (15,16) or in controlled experiments (17). These results show that monthly topical administration of selamectin is effective against flea infestation of dogs and cats housed in heavily flea-infested environments and also prevented the establishment of an environmental infestation, even when fleas are introduced into conditions that are highly suited for their development.

Multi-center field studies were conducted in veterinary clinics in Europe ( UK, France, Germany and Italy ) and the USA. Dogs and cats infested with fleas presented at the clinics were treated with commercial selamectin formulation at presentation and subsequently after 30 and 60 days. Flea counts and clinical observations were made on days 14,30,60 and 90. The animals designated as the control group were treated with a fention (cholinesterase inhibitor organophosphorus insecticide) preparation accompanied in some of the cases with the use of an environmental spray containing insect growth regulator and pyrethroid insecticide. An environmental spray was not used with selamectin. Treatment of control animals with inactive ingredient was not applicable in the veterinary field study because of ethical considerations. Cats in the USA experiment were treated topically with pyrethroids. Dogs and cats treated with selamectin showed a reduction of infestation between 90.7% and 99.8% for the whole period of observation. Slightly lower percentages of reduction were obtained with fention combined with pyrethrins and insect growth regulator environment treatment (18). In pyrethrin-treated cats fleas were reduced by 66.4% to 81.3% (19). In the USA, supplementary clinical criteria such as pruritus, erythema, scaling, alopecia, papules and dermatitis were used to evaluate the beneficial results of selamectin treatment. A significant proportion of flea-infested animals develop hypersensitivity to flea allergens resulting in dermatitis. This condition is difficult to treat, because exposure to small numbers of fleas may provoke a significant reaction. The percentage of dogs and cats showing these dermatological conditions decreased significantly in selamectin treated animal compared to the animals treated with other preparations. However a total cure of all dermatological manifestations could not be achieved during the experimental observation period (19).

Introduction Efficacy against fleas Efficacy against ticks efficacy against nematodes Safety of selamectin

Efficacy against mites
Sarcoptic mange

Sarcoptes scabiei is a parasitic mite that borrows into the skin of animals and man causing a disease condition known as scabies or sarcoptic mange. The mites of this species, that may be found on different hosts, are usually regarded as being a variety of the species S. scabiei that are physiologically adapted to one or more usual hosts, but can live, temporarily at least, on other unusual hosts. Adult mites penetrate initially the skin of a new host by attaching to the skin with the suckers of the two first pair of legs and then cutting the skin with the helicera and the cutting-hooks of the last segment of the first two pairs of legs. The mite usually borrows below the horny layer of the skin (Stratum corneum). The burrows contain male and female mites, their feces, their eggs, hatched larvae and nymphs. Eggs laid in the burrow hatch in 3-5 days. Six days later the six-legged larva molt and become an eight-legged nymph and the latter molt to adult female or male mites. Two stages of females are known, a first pubescent female that moult two days later to a mature (ovigerous) female. The whole life history from egg to mature female takes about two weeks. All developmental stages of S. scabiei, except the egg, create burrows in the skin.

Canine scabies is a severely debilitating highly contagious condition, which spreads through close contact between infested dogs or by contaminated fomites (20). The mites suck the tissue fluid of the host and eventually feed on the horny cells. They cause marked irritation of the skin and itching, which provokes scratching or biting of the skin. Red papules and vesicles appear on the skin that are followed by appearance of crusts formed of dry lymph. The connective tissue of the skin proliferates and keratinisation is increased so that the skin becomes thickened and wrinkled. The hair that are deprived of blood supply fall out creating bald patches. Secondary bacterial infection makes the condition worse and when large areas of skin are affected progressive emaciation and eventually death occur. S. scabiei is considered to be a frequently transmitted zoonotic agent (21). Forty two dogs with naturally acquired infestation of S. scabiei obtained from commercial dog kennels where an outbreak followed an inadvertent introduction of infested dogs (USA) or from a private hunting kennel which experienced an outbreak of scabies (Europe) were treated on day 0 and day 30 with selamectin at the recommended dose and or with an inert vehicle mixture. Counts of S.scabiei from skin scrapings were performed every 14-15 days up to 60 days after treatment. S.scabiei mites were reduced 93.5 % (USA) and 98.1 % (Europe) on the first count after treatment and by 100 % for all remaining counts. There was a clear reduction of the severity of the clinical signs for the selamectin treated dogs compared with those treated with the vehicle mixture (22).

In another study dogs and cats presented at veterinary clinics in the USA and Europe were treated against scabies infection with selamectin or other insecticides containing phosmet or amitraz or N-(mercaptomethyl) phthalimide S-(0,0-dimethyl phosphoro-didithioate). No S. scabiei were detected in over 95 % of the selamectin treated dogs, 30 days after a single dose and no mites were recovered from any of the selamectin treated dogs after the second treatment. A dramatic improvement in all six clinical signs of S. scabiei (pruritus, erythema, crusting, papulae, alopecia and pyodermatitis) was observed in the course of treatment. Similar results were achieved with the control products while repeat treatments were necessary to control the infestation. When a dog is diagnosed with S. scabiei infestation it is recommended that all dogs in contact also be treated irrespective of whether they are showing clinical signs (23).

Ear mange

Otodectes cynotis is a psoroptic mite, which inhabits the depths of the ear canal, near the eardrum, of dogs, cats and some other carnivores. Otodectes are non-borrowing mites that complete their life cycle (egg to egg), in about two weeks (minimum 11 days), on the skin of the host. The larva molts in 2-4 days to a protonymph, which is followed by a tritonymph the latter giving rise to an adult male or immature female. Female tritonymph attach to the male and remain so until they molt into mature (ovigerous) females when insemination occurs. A female lives 2 to 6 weeks and lay 30-40 eggs.

This mite sucks the host tissue fluid, causing inflammation and exudate of lymph and the formation of crusts in the ears. Dogs begin to suffer earlier than cats which are affected only after the disease is well established. The affected animal shakes its head and scratches at the base of the ears and this symptom may be followed by a discharge from the ears. Torticollis may result, or the animal may turn in a circle or suffer from convulsions and epileptiform fits. Bacterial infection of the ear may lead to ulceration and perforation of the ear drum with resultant infection of the internal ear and possibly of the brain. Human infestations by the dog ear mite have been reported (24).

The efficacy of the commercial preparation of selametin in the treatment of naturally acquired aural infestation of O. cynotis on dogs and cats was evaluated under experimental conditions in 48 dogs and 32 cats. The cats received one treatment and the dogs two treatments, one month apart. Percentage reductions in mean mite counts for selamectin treatment compared to the dogs and cats treated with vehicle solution were 100% for all animals on all counts (24). In a field study with a variety of breeds and ages, dogs (83) and cats (144) presenting as clinical cases in veterinary practices in USA and Europe (UK, France and Italy) were treated by topical application of selamectin at the base of the neck or by other approved otic preparations (positive control group) instilled directly in the external ear canal. Selamectin eliminated mites in cats 94.3 % (Europe) and 100 % (USA), versus 87.9 % and 92.9 % respectively by the instilled otic products. In dogs the percentages of efficacy were 90.4 % for selamectin and 65 % for otic products (23).

Otic preparations currently available for treatment of ear mites require daily applications for up to four weeks, while the otitis causes acute pains whenever the ears are handled. The topical application of selamectin on an unaffected area of the body and the prolonged activity after application circumvent the above posology.

Introduction Efficacy against fleas Efficacy against mites efficacy against nematodes Safety of selamectin

Efficacy against ticks
R. sanguineus (the brown dog tick) belongs to the family Ixodidae (hard ticks) which are large blood-sucking acari with a terminal capitulum in all stages and a dorsal shield (scutum) which shows sexual dimorphism - small in the female and almost covering the dorsal surface in the male. This tick species parasitizes mainly dogs and other canines but it may feed on a wide variety of mammals including man and also birds. Domestic cats are infrequent hosts of this tick. R. sanguineus is one of the most widespread ticks in the world and causes heavy infestation of dogs in Israel. It may appear as an urban tick infesting homes and kennels or as a field tick feeding on rodents, hares, hedgehogs, domestic animals, wild carnivores and dogs. In the Mediterranean coastal area it readily attaches to man (25).

There are four stages in the life cycle of hard ticks: egg, larva, nymph and adult. The female drops off its vertebrate host and seeks a sheltered site to lay a single large batch of 2 to 4 thousand brown globular eggs, after which she dies. Depending upon environmental conditions the eggs hatch in two weeks to several months giving rise to a hexapod larva. Each of the parasitic stages engorge on a host and then drop on the ground, the larva and nymph in order to molt, and the adult female for oviposition. Unfed larvae or nymphs may survive for about six months without a meal, and adults for more than one year, though two or three generations a year seem to occur in subtropical areas. According to environmental conditions, the length of the life cycle of this tick may be a minimum of two months to a maximum of more than one year. As they feed, ticks alternate between imbibing blood components present in the feeding lesion, and returning excess fluid back to the host via saliva, thus concentrating on the blood meal nutrients and regulating haemolymph volume and ionic composition (26).

R. sanguineus transmits many pathogens among dogs and other vertebrates: Babesia canis and B. vogeli, Hepatozoon canis, Rickettsia conori, R. canis, R. rickettsii, Ehrlichia canis, Pasteurella tularensis, Borrelia hispanica and Coxiella burnetti. In Israel this tick species appears to be the sole vector of canine babesiosis, hepatozoonosis and ehrlichiosis, and is responsible for the transmission of the Israeli-Mediterranean spotted fever (caused by R. conori) (25). Saliva of R. sanguineus has a marked immunosuppresive activity by impairing T cell-proliferation, antigen presentative and IFN-g induced macrophage microbicidal activity (26). A series of controlled studies was conducted to investigate the efficacy of selamectin against weekly infestation with 50 adult R. sanguineus. A two-week interval treatment regimen provided an efficacious control against this tick. Monthly treatment with selamectin was also effective and the addition of a treatment at 14 days after the first treatment improved efficacy, particularly in the several weeks following the additional treatment (27). Selamectin controlled also against the American dog tick (Dermacentor variabilis), which is not present so far in Israel. This drug, however, has no practical repellent activity as shown by a test with Ixodes ricinus ticks (28).

Efficacy against nematodes
Three species of ascarids are commonly found in Israel: Toxocara canis (infecting dogs), Toxocara cati (infecting cats), and Toxascaris leonina (infecting dogs and cats). The adult females of this worm may reach a length of 18 cm for T. canis and 10 cm for the other two species. Transmission in all species may be direct by ingesting eggs or transuterine by larvae from the tissues of infected females to the fetuses. The life cycle of the ascarids comprises eggs produced by the female and five larval stages that develop in various organs and the intestine of the host.

A female may lay about 200.000 eggs per day, which are excreted in the feces of the host and shed in the environment. An infective larval stage develops within the eggs on the ground in 3-7 days between a wide temperature range (150 to 350 C). The eggs which posses a thick protective shell may survive in the environment for more than one year. After ingestion by the host, the eggs hatch to release the second stage larva. Extensive somatic and tracheal types of migrations of the larvae occur before they develop to adults. The larvae migrate from the intestine through the liver to the lungs and then through the trachea and the oesophagus to the intestine.

Prenatal infection is extremely common in T. canis infection, however infection occurs also by ingestion of eggs by adult dogs as well as by young puppies. After the initial infection larvae are able to remain dormant in the bitch in various tissues for nearly all her lifetime and she may transmit infection to several litters. Coprologic examination of bitches infected with tissue larvae may show negative results, however, they are still capable of transmitting infection to their progeny. Activation of the larvae in the bitch, followed by migration to the fetus, occurs usually around the 42nd day of pregnancy and third stage larvae (1.0 mm of length) are found in the lungs of the fetuses before birth. A molt to the fourth larval stage (5-7 mm) occurs in puppies during the first week after birth when they are found in the intestine. Throughout the second and third week after birth a fifth larva stage grow rapidly to become an adult worm.

Rodents and some invertebrates are susceptible to Toxocara and Toxascaris infections and second stage larvae that develop in these paratenic hosts may infect dogs and cats predating on infected mice or cockroaches.

Ascarids are particularly injurious to puppies and kittens. The commonest signs are unthriftiness, digestive disturbances, bloated and pot bellied appearance. Puppies with heavy prenatal infection with T. canis suffer from mucoidal diarrhea, show frequent vomiting and occasionally die from intestinal obstruction or perforation. Anemia and nervous disturbances are observed although no satisfactory explanation for this manifestation exists. Migration through the lungs may trigger pneumonia which is complicated by secondary infections.

Toxocariasis in man (observed mostly in children) is caused mainly by T. canis, but also T.cati and T.leonina have been incriminated. The visceral larva migrans symptoms are provoked by lesions in the brain, eyes or other organs and are accompanied by persistent eosinophilia. Ocular larva migrans causes granulomatous inflammation, which may result in a variety of other clinical symptoms including keratitis, iridocyclitis, chronic endophthalmitis and detached retina. Treatment with antinematodal drugs (diethyl carbamazine, thiabendazole, mebendazole) has little effect and may worsen the situation by killing the parasite in situ.

The efficacy of selamectin against experimentally induced and naturally acquired T. canis and T. leonina in dogs was evaluated in controlled and field studies. For induced infections, there were significant reductions in the mean numbers of adult

T. canis after a single application of selamectin( 93.9 - 98.1 %), after two monthly applications (88.3 - 98.6 %), and 100 % after three monthly applications. In the naturally infected dogs in the controlled studies, when selamectin was administered twice at an interval of 30 days, the percentage of reductions in mean numbers of adult T. canis at necropsy were 84.6, 91.3, and 97.9%. When selamectin was adminitered on days 0, 14, and 30, the percentage reductions were 91.1 and 97.6 %. Mean fecal T. canis eggs counts were reduced by > 92.9 % at the end of the controlled studies. In the field studies mean fecal egg counts were reduced by 89.5 and 95.5%, for 14 and 30 days respectively after a single treatment with selamectin, and by 94.0 %, 30 days after the second treatment with selamectin (29). To prevent intrauterine infection of pups endemically infected with T. canis, bitches were treated with selamectin at presumed 40 and 10 days before parturition and 10 and 40 days after parturition (selamectin was not given to the pups). A reduction in egg count of 99.7 % in the bitches and 96.1 to 98.2 % in the pups was observed following treatment compared to the infestation recorded in the dogs treated with inactive ingredients. It appears that somatic larvae that are usually reactivated during the last three weeks of pregnancy (and migrate through the placenta ) were killed by selamectin before being established in the fetus. The treatment also prevented possible milk infestation of the pups (30).

In cats a study of the efficacy of selamectin against experimental (500 embryonated eggs, 56 days prior to treatment) and naturally acquired infections with T. cati was carried out by a count of adult worms at necropsy, performed 14 days after treatment. A single application of selamectin provided 100 % reduction in adult worms for both experimentally and naturally acquired infections (31).

Ancylostominae (hookworms) are strongylid nematodes with a well-developed buccal capsule armed on its ventral margin with teeth or chitinous cutting plates. Eggs of A. tubaeforme have been detected at coprologic examinations of cat feces in Israel. The life cycle of this parasite includes a larva that hatches on the soil and becomes infective in about one week and four stages that develop in the host. Infection is oral or by skin penetration, a prenatal (intra-uterine) and lactogenic (colostral) similar to the A. caninun pathway were also suggested. A. tubaeforme is a voracious bloodsucker and anemia accompanied by iron depletion is the principal consequence of its infestation. Topical treatment with selamectin of cats infected with A. tubaeforme only or cats carrying both A. tubaeforme and T. cati was highly effective in naturally acquired or experimentally induced infections (31).

A total of 19 veterinary practices in USA, France, Germany and Italy participated in a series of studies including 298 cats of various ages and breeds that carried one or more of the following parasites: Toxocara cati, Toxascaris leonina, Ancylostoma spp. and Uncinaria stenocephala. Cats with confirmed, by egg count, ascarid and hookworm infections were treated twice with commercial preparation of selamectin at monthly intervals. Two additional quantitative fecal examinations were performed on days 30 and 60 after the treatment. A reduction of the pretreatment individual count of 99 % to total disappearance of eggs from the feces was observed at the second and third quantitative counts (32).


Heartworm (Dirofilaria immitis) is a nematode that can reach 25 - 30 cm in length mainly in the right ventricle of the heart and pulmonary artery of dogs, cats and wild canids. The female worm is ovoviviparous and microfilariae may be found in the blood during the whole period of the infection. This parasite is transmitted by several genera of mosquitoes (intermediate hosts) in which it undergoes development and migration. Maturity in the final host is reached about five months after infection. Selamectin was 100% effective in preventing heartworm development in dogs when administered as a single topical dose 30, 45, or 60 days after infection in laboratory and field studies. A single dose also induced total protection in cats. Selamectin remained 100 % effective at half (3.0 mg/kg) the recommended dosage (33,34). Autochthonous infection with heartworm has not yet been diagnosed in Israel, but selamectin treatment can be administered when pets are taken to endemic areas.

Introduction Efficacy against fleas Efficacy against mites Efficacy against ticks efficacy against nematodes

Safety of selamectin
The clinical safety of selamectin was evaluated in oral and topical application of single and multiple doses to dogs and cats of various ages, breeds and physiological conditions.

Safety in dogs

In a margin safety study 20 male and 20 female 6 weeks old beagles received topical application of saline or 1x, 3x, 5x, and 10x multiples of the unit dosage (6 mg/kg) of selamectin for a total of 7 treatments. Despite the extremely high dosages in some of the treated animals none displayed clinical or neurologic signs or developed clinical or pathological abnormalities as a result of the treatment.

In 12 dogs (including saline treated controls) a single unit oral dose of selamectin caused no adverse effects or signs of toxicosis during 30 days after application. In reproductive safety studies, fertility of each animal was proven by siring or bearing at least two litters of four or more pups per litter. Female dogs were treated every 28 days with a 3x multiple dosage unit of selamectin before mating. After mating treatment was adjusted to the day of mating or 15 days after mating until the pups were weaned at 6 weeks of age. Male dogs received every two weeks a 3x multiple unit dosage (a total of 17 dosages) until each male had mated with two females in estrous. Conception rates and whelping indices (number of total live pups/ number of pregnant animals per treatment) for both control and selamectn treated male dogs were similar. Conception rates of females were 90 % for the selamectin treated versus 90 and 100 % in the controls in the various experimental groups. About the same numbers of non-viable pups and perinatal death were observed in litters of treated and control beaches. None of the pups had congenital abnormalities (35).

Rough-coated Collies are more sensitive to central nervous system toxicity associated with avermectins (36). A single topical dose of 40 mg/kg selamectin produced no abnormalities in avermectin-sensitive Collies. Three treatments every 28 days with five times the recommended dosage of selamectin or with saline resulted in sporadic mild salivation in both groups (35).

Special attention was paid to the safety of selamectin treatment in animals suffering from parasite burden. Neither adult heartworms nor circulating microfilariae posed risk when selamectin was administered topically at three times the recommended dose (35). In a total of 648 doses of selamectin administered to 168 dogs infested with the dog tick only some of them displayed mild salivation about two hours after the first treatment (27). No adverse reactions in dogs were observed in five consecutive treatments aimed to prevent repeat flea infestations (19), or in animals infected with gastrointestinal nematodes (32).

Safety in cats

Safety of selamectin to cats was tested in a similar experiment to the dog safety studies. Topical application of up to 10 times the recommended dose to six week and adult cats, and to fertile female and male cats yielded no evidence of toxicosis. Oral administration of the topical solution to cats provoked transient salivation and intermittent vomiting for up to 56 h after dosing, but cats exhibiting these signs recovered completely without supportive medication. Selamectin had no adverse effects on clinical pathology markers of liver and kidney functions of cats with multiple unit doses (37).

Selamectin is a single broad-spectrum parasiticide that combines anti-arthropod with anti-nematodal activity (1). It kills more than 98% of the fleas present on the host within 24 to 36 h of application. It also breaks the life cycle by killing adult fleas and flea eggs and by reducing maturation of eggs to larvae and adults. Monthly treatment not only directly protected host animals from flea infestation but also interrupted the flea’s breeding cycle and severely diminished the residual population of fleas in the household environment. Elimination of mange and ear mites is achieved by two topical applications one month apart. Monthly treatment with an additional treatment at 14 days after the first treatment proved a high efficacy against the wide spread brown dog tick in Israel. Selamectin acted as an effective drug against hookworms and ascarids by eliminating more than 99% of the roundworm intestinal burden. It represents the only “spot on” that is active against external and internal parasites and has a therapeutic effect in pups nursing on selamectin treated dams. Successful treatment of pests and worms in domestic pets as well as improving animal health contributes to promoting public health by decreasing or eliminating the risk of zoonotic infections.

Selamectin possesses a high safety profile in six weeks old and older puppies and kittens, in breeding dogs and cats, in ivermectin sensitive breeds, in heavily parasitised animals with ecto- and endo-parasites and heartworm, and following accidental oral ingestion by treated animals. It is the only “spot on” recommended for 6-week old pups.
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