What is Comboline® Spot-On for Cats and Cats and Ferrets? Topical external antiparasitic solution for cats and ferrets Pharmaceutical form Spot-on solution (Sol.udp) Composition per pipette (0.5 ml): Fipronil 50 mg; (S)-methoprene 60 mg. Excipients: Butylhydroxyanisole (E 320) 0.1 mg; butylhydroxytoluene (E 321) 0.05 mg. Pharmacological properties Pharmacotherapeutic group: topical ectoparasiticides QP53. Pharmacodynamic properties: Fipronil is an insecticide/acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those regulated by the neurotransmitter gamma-aminobutyric acid (GABA), blocking the pre- and postsynaptic transfer of chloride ions across the cell membrane. This leads to uncontrolled activity of the central nervous system and the death of insects and mites. Fipronil kills fleas within 24 hours and ticks (Dermacentor variabilis, Rhipicephalus sanguineus, Ixodes scapularis, Ixodes ricinus, Haemaphysalis longicornis, Haemaphysalis flava, Haemaphysalis campanulata) and lice within 48 hours of exposure. (S)-Methoprene is an insect growth regulator (IGR) belonging to the class of compounds known as juvenile hormone analogues, which inhibit the development of insects in immature stages. This compound mimics the action of juvenile hormone, resulting in abnormal development and death at various stages of flea development. The ovicidal activity of (S)-methoprene occurs both by direct penetration of freshly laid eggshells and by absorption through the cuticle of adult fleas. (S)-methoprene is also effective in preventing the development of flea larvae and pupae, thus preventing contamination of the environment of treated animals by immature fleas. Pharmacokinetic data Studies on the metabolism of fipronil have shown that the main metabolite is the sulfonic derivative of fipronil. (S)-Methoprene is extensively degraded into carbon dioxide and acetate, which are then incorporated into endogenous materials. The pharmacokinetic profiles of fipronil and (S)-methoprene in combination were studied in cats after topical application, compared to intravenous administration of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters under similar clinical conditions. Topical application, with potential additional oral exposure via licking, resulted in low systemic absorption of fipronil (18%), with a mean maximum concentration (Cmax) of approximately 100 ng/ml fipronil and 13 ng/ml of its sulfone derivative in plasma. Maximum plasma concentrations of fipronil are reached rapidly (mean Tmax of approximately 6 hours) and decline with a mean terminal half-life of approximately 25 hours. Fipronil is readily metabolised to fipronil sulfone in cats. Plasma concentrations of (S)-methoprene after topical application to cats were below the limit of quantification (20 ng/ml). (S)-Methoprene and fipronil, together with their main metabolite, are effectively destroyed from the cats fur one day after application. Concentrations of both fipronil and its sulfone derivative, as well as (S)-methoprene, in the fur decline over time and are detectable for at least 59 days after treatment. Parasites are killed by contact rather than systemic exposure. No drug interactions were observed between fipronil and (S)-methoprene. The pharmacokinetic profile of the veterinary medicinal product has not been investigated in ferrets. Interactions and incompatibilities None are known. InstructionsCats : Can be used against flea infestations, alone or in combination with ticks and/or biting lice. - Elimination of fleas (Ctenocephalides spp.). Insecticidal efficacy against new infestations of adult fleas persists for 4 weeks. Prevents flea multiplication by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) from eggs laid by adult fleas for six weeks after application. - Elimination of ticks (Ixodes ricinus, Dermacentor variabilis, Rhipicephalus sanguineus). It has an acaricidal efficacy of up to 2 weeks against ticks (based on experimental data). - Elimination of biting lice (Felicola subrostratus). It can be used as part of a treatment strategy to control flea allergy dermatitis (FAD). Ferrets : Can be used against flea infestations, alone or in combination with ticks. - Elimination of fleas (Ctenocephalides spp.). Insecticidal efficacy against new infestations of adult fleas persists for 4 weeks. Prevents flea multiplication by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) that originate from eggs laid by adult fleas. - Elimination of ticks (Ixodes ricinus). It has an acaricidal efficacy that persists for up to 4 weeks against ticks (based on experimental data). Contraindications In the absence of available data, it should not be used in kittens less than 8 weeks of age and/or weighing less than 1 kg. It should not be used in ferrets less than 6 months of age. Do not use in sick animals (systemic diseases, fever, etc.) or convalescent animals. Do not use in rabbits as adverse reactions, including death, may occur. In the absence of studies, use in species other than the target species is not recommended. Do not use in case of hypersensitivity to the active substances or any of the excipients. Adverse reactions Administer the recommended dose. Very rare adverse reactions reported include transient skin reactions at the application site (desquamation, local hair loss, itching, redness) as well as generalised itching or hair loss. Excessive salivation, reversible nervous system signs (increased sensitivity to stimulation, depression, other nervous system signs) or vomiting have also been observed. In case of licking, a short period of excessive salivation may be observed, mainly due to the nature of the excipient. Route of administration Solution for spot-on application. dOSAGECats : One pipette of 0.5 ml per cat, corresponding to the minimum recommended dose of 5 mg/kg of fipronil and 6 mg/kg of (S)-methoprene, by topical application to the skin. In the absence of safety studies, the minimum treatment interval is 4 weeks. Ferrets : One pipette of 0.5 ml per ferret, corresponding to a dose of 50 mg fipronil and 60 mg (S)-methoprene per ferret, by topical application to the skin. The minimum treatment interval is 4 weeks. Method of administration Hold the pipette upright. Tap the narrow end of the pipette gently to ensure that the contents are in the main body. Open the tip. Part the animals fur at the base of the neck, in front of the shoulder blades, until the skin is visible. Place the tip of the pipette on the skin and squeeze the pipette several times until the contents are completely emptied directly onto the skin in one spot. Special precautions for use in animals : It is important to ensure that the veterinary medicinal product is applied to an area where the animal cannot lick it and that animals do not lick each other after treatment. No data are available on the effect of immersion in soap/water baths on the efficacy of the veterinary medicinal product in cats or ferrets. However, based on the available information on dogs being shampooed starting 2 days after application of the veterinary medicinal product, it is not recommended to bathe animals within two days of application. Ticks can attach themselves. For this reason, the transmission of infectious diseases cannot be completely ruled out if conditions are unfavorable. Fleas on animals often infest baskets, bedding and their resting areas, such as carpets and certain types of furniture, which should be treated, in case of massive infestation, with an appropriate insecticide at the beginning of control measures and cleaned regularly with a vacuum cleaner. No data are available on the potential toxicity of this veterinary medicinal product in kittens under 8 weeks of age that come into contact with a treated cat. In this case, special care is recommended. Specific precautions to be taken by the person administering the veterinary medicinal product to animals: This veterinary medicinal product may cause irritation of the eyes, skin and mucous membranes. Therefore, contact of the veterinary medicinal product with the mouth, skin and eyes should be avoided. People with known hypersensitivity to insecticides or alcohol should avoid any contact with the veterinary medicinal product. Avoid contact of the veterinary medicinal product with fingers. If this happens, wash hands with soap and water. After accidental eye contact, rinse eyes gently with water. Wash hands after use. Treated animals should not be touched until the application site of the veterinary medicinal product is dry and children should not be allowed to play with treated animals until the application site is dry. It is therefore recommended that animals should not be treated during the day but rather at dusk and that recently treated animals should not sleep with their owners, especially children. Use during pregnancy and lactation: Cats : Can be used during gestation. Ferrets : The safety of this product in ferrets during pregnancy and lactation has not been established. Use only according to the benefit/risk assessment by the responsible veterinarian. Storage method Do not store above 30°C. Store in the original packaging. Observations Veterinary medicines without a prescription.