Acta Veterinaria Scandinavica BioMed Central Review Open Access A review of the off-label use of selamectin (Stronghold®/Revolution®) in dogs and cats Maggie A Fisher*1 and David J Shanks2 Address: 1Shernacre Enterprise, Shernacre Cottage, Lower Howsell Road, Malvern, Worcs WR14 1UX, UK and 2Peuman, 16350 Vieux Ruffec, France Email: Maggie A Fisher* - [email protected]; David J Shanks - [email protected] * Corresponding author Published: 25 November 2008 Received: 7 January 2008 Accepted: 25 November 2008 Acta Veterinaria Scandinavica 2008, 50:46 doi:10.1186/1751-0147-50-46 This article is available from: http://www.actavetscand.com/content/50/1/46 © 2008 Fisher and Shanks; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Since its introduction approximately seven years ago, selamectin (Stronghold®/Revolution®, Pfizer Inc.) has been used off-label to treat a number of ecto- and endoparasite conditions in dogs and cats. It has been used as a successful prophylactic against Dirofilaria repens and as a treatment for Aelurostrongylus abstrusus in cats. It has also been used to treat notoedric mange, infestation with the nasal mite Pneumonyssoides caninum, Cheyletiella spp. and Neotrombicula autumnalis infestations and larval Cordylobia anthropophaga infection. However, to date attempts to treat generalised canine demodicosis have not been successful. In all cases, treatment was apparently well tolerated by the host. Background [3]. Higher doses of ivermectin, which might have pro- Until relatively recently, the antiparasitic products availa- vided a broader spectrum of activity allowing control of ble to the veterinarian were often inadequate [1]. During more parasite species, were unattainable because of idio- the last two or three decades however, remarkable syncratic toxic reactions in some breeds of dog [4]. There- progress has been achieved in some areas of parasite con- after a systematic programme to evaluate avermectin trol through better understanding of the behaviour and analogues resulted in the discovery of the macrocyclic lac- lifecycles of the target parasites and the introduction of a tone selamectin, which was shown to have efficacy and new generation of antiparasitics [1,2]. By the end of the safety profiles which warranted its commercialisation for last decade of the twentieth century avermectins (for cats and dogs [5]. example ivermectin and doramectin) and milbemycins (for example moxidectin), because of their activity against During the pre-development evaluation of the safety and both endoparasites and ectoparasites, had become well efficacy of selamectin in dogs and cats, the compound was established as endectocides for the treatment of livestock. administered topically and orally at various intervals and The development of the equivalent products for cats and dosages and its efficacy against target endo-and ectopara- dogs evolved more slowly, perhaps because companion sites was assessed. In studies conducted early in the dis- animals were not the priority for pharmaceutical develop- covery and development process, selamectin was ment initially. The first avermectin-based product administered orally in some studies and topically in oth- approved for use in companion animals was a low-dosage ers. These studies demonstrated conclusively the efficacy formulation of ivermectin solely for the prevention of of the compound, when applied topically, against both adult heartworm (Dirofilaria immitis) infestations in dogs endoparasites (larval Dirofilaria immitis), and against Page 1 of 5 (page number not for citation purposes) Acta Veterinaria Scandinavica 2008, 50:46 http://www.actavetscand.com/content/50/1/46 ectoparasites (Ctenocephalides felis); oral administration under the cascade system detailed in Directive 2001/82/ showed activity against a range of parasites: Ancylostoma EC, modified by 2004/28/EC. Such treatments are com- caninum, A. tubaeforme, Toxocara canis, T. cati, Uncinaria monly referred to as "off-label" treatments. In common stenocephala, Toxascaris leonina, Rhipicephalus sanguineus with most other veterinary products, there have been a and Dermacentor variabilis [5]. These early studies also con- number of published reports of the extra-label use of the firmed the excellent safety profile of selamectin, even commercialised topical formulation of selamectin against when administered orally to ivermectin-sensitive collies different parasites in the dog and cat; the purpose of this [5-7]. Further investigations demonstrated that topical communication is to review these various reports and to application of a minimum of 6 mg selamectin per kg bod- discuss their implications for the current and future use of yweight gave prolonged efficacy against fleas [8] and the this important anti-parasitic product. same dose-rate was effective in preventing the establish- ment of heartworm in dogs and cats [9]. After the success- Endoparasites ful completion of a global development programme, the Endoparasite activity of selamectin is exerted against nem- topical formulation of selamectin was registered and is atodes and it is in this area that the commercial product now marketed throughout the world (as either Strong- has been demonstrated to be effective. hold® or Revolution®, depending upon geographical region) as a topical product with a broad claims structure There are believed to be five species of Dirofilaria world- including a number of endo- and ectoparasites, for use on wide and now that the control of D. immitis, the most dogs and cats at a dose of at least 6 mg/kg (Table 1); it is important filarioid parasite of dogs and cats, is common commercialised in colour-coded tubes containing differ- practice in heartworm-endemic areas, attention is moving ent amounts and different concentrations of the active to the importance of other species of Dirofilaria. D. repens, ingredient, each suitable for animals in a defined weight which is endemic in southern areas of Europe, infects band. mainly dogs but can also infect cats. Adult worms are found most often in the subcutaneous connective tissue Although the minimum dose-rate of 6 mg/kg is identical [11]. Infection may be asymptomatic, being discovered for cats and dogs, there is evidence from pharmacokinetic only when microfilariae are found in routine testing for D. studies that the topical treatment of cats resulted in immitis infection but infection has also been associated approximately 50 times higher levels of selamectin within with pruritic dermatitis in some animals [11]. Moreover, the animal compared to dogs [10]. This marked species as humans can also become infected, the parasite has difference is probably due to a series of factors including important public health implications [12]. Genchi and a greater flux through cats' skin than that of dogs and met- co-workers [13] have recently reported that the commer- abolic differences [10]. The higher bioavailability in cats cial formulation of selamectin administered at monthly may explain why selamectin appears effective against a intervals according to label recommendations to prevent broader range of endoparasites in cats than in dogs; for the establishment of D. immitis infections in dogs living in example, it is effective, when applied topically, against A. a D. repens endemic area and thus exposed to a high risk tubaeforme, the hookworm of cats, but not against A. cani- of infestation, was 100% successful in preventing the num, the hookworm of dogs [5]. establishment of D. repens infection in 65 dogs; whilst 11 of 27 (41%) untreated controls in this study were shown In the EU, veterinary surgeons can prescribe veterinary or to be infected following the transmission season, equating even human medicines for dogs and cats to treat condi- to an approximate incidence rate of 0.5116 per animal tions where there is no specific label recommendation season at risk. Table 1: Summary of label claims for selamectin in Europe Dogs and cats: Treatment and prevention of flea (Ctenocephalides spp.) infestations including use as part of a treatment strategy for flea allergy dermatitis and may assist in the control of existing environmental flea infestations in areas to which the animal has access Treatment of ear mite (Otodectes cynotis) infection Heartworm (Dirofilaria immitis) prevention Dogs for the treatment of: Adult Toxocara canis Sarcoptes scabiei (sarcoptic mange mites) Trichodectes canis (biting lice) Cats for the treatment of: Adult Toxocara cati Adult hookworm (Ancylostoma tubaeforme) Felicola subrostratus (biting lice) Page 2 of 5 (page number not for citation purposes) Acta Veterinaria Scandinavica 2008, 50:46 http://www.actavetscand.com/content/50/1/46 Aelurostrongylus abstrusus infects the lungs of cats and has scenting ability [19]. The mite occurs worldwide but is a worldwide distribution; in areas where the infection is particularly common in Scandinavia, where 20% of dogs endemic up to 90% of cats may be infected [14,15]. Infec- in Sweden were found to be infected in a post-mortem tion may be asymptomatic or may cause clinical signs, survey [19]. Diagnosis in the living dog is difficult as the typically including severe coughing and respiratory dis- mites do not inhabit the easily visualised part of the nasal tress.