What is Comboline® Spot-On for Cats and Cats and Ferrets? External antiparasitic topical 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, particularly those regulated by the neurotransmitter gamma-aminobutyric acid (GABA), blocking the pre- and postsynaptic transfer of chloride ions across the cell membrane. This results in uncontrolled central nervous system activity 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 analogs, which inhibit the development of immature insect stages. This compound mimics the action of juvenile hormone, resulting in abnormal development and death at various flea developmental stages. The ovicidal activity of (S)-methoprene occurs both through direct penetration of freshly laid eggshells and through absorption via the cuticle of adult fleas. (S)-Methoprene is also effective in preventing the development of flea larvae and pupae, thereby preventing contamination of the treated animals environment by immature flea stages. Pharmacokinetic data Studies of fipronil metabolism have shown that the main metabolite is the sulfone 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 the absorption and other pharmacokinetic parameters under similar clinical conditions. Topical application, with the additional potential oral exposure from licking, resulted in low systemic absorption of fipronil (18%), with a mean maximum concentration (Cmax) of approximately 100 ng/ml of fipronil and 13 ng/ml of its sulfone derivative in plasma. Peak plasma concentrations of fipronil are reached rapidly (mean Tmax approximately 6 h), and decline with a mean terminal half-life of approximately 25 h. Fipronil is slightly metabolized to fipronil sulfone in cats. Plasma concentrations of (S)-methoprene after topical application in cats were below the limit of quantification (20 ng/ml). (S)-Methoprene and fipronil, along with their main metabolite, are effectively destroyed by cats fur one day after application. Concentrations of both fipronil and its sulfone derivative, as well as (S)-methoprene, in the fur decrease over time and are detectable for at least 59 days post-treatment. The parasites are killed by contact rather than systemic exposure. No drug interaction has been observed between fipronil and (S)-methoprene. The pharmacokinetic profile of the veterinary medicinal product has not been investigated in ferrets. Interactions and incompatibilities None 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 by adult fleas persists for 4 weeks. Prevention of flea multiplication by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) originating 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 the treatment strategy for the control of 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 by adult fleas persists for 4 weeks. Prevention of 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 on kittens less than 8 weeks old and/or weighing less than 1 kg. It should not be used on ferrets less than 6 months old. Do not use on sick (systemic disease, fever, etc.) or convalescent animals. Do not use on rabbits, as adverse reactions, including death, may occur. In the absence of studies, it is not recommended to use it on species other than the target species. Do not use in cases of hypersensitivity to the active substances or to any of the excipients. Adverse reactions Administer the recommended dose. Very rare adverse reactions that have been reported include transient skin reactions at the application site (scaling, local hair loss, itching, redness) as well as generalized 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 brief period of excessive salivation may be observed, mainly due to the nature of the excipient. Route of administration Solution for spot-on application. PosologyCats : One 0.5 ml pipette 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 0.5 ml pipette per ferret corresponding to a dose of 50 mg of fipronil and 60 mg of (S)-methoprene per ferret, by topical application to the skin. The minimum treatment interval is 4 weeks. Administration method Hold the pipette upright. Tap the narrow end of the pipette to ensure the contents are in the main part. 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 a single spot. Special precautions for use in animals : It is important to ensure that the veterinary medicine is applied to an area where the animal cannot lick it and that the animals do not lick each other after treatment. No data are available on the effect of immersion in water/soap baths on the efficacy of the veterinary medicinal product in cats or ferrets. However, based on available information regarding dogs bathed with shampoo starting 2 days after application of the veterinary medicinal product, bathing animals within two days of application is not recommended. Ticks may attach on their own. For this reason, the transmission of infectious diseases cannot be completely ruled out if conditions are unfavorable. Fleas on animals often infest their baskets, bedding, and resting areas, such as carpets and certain types of furniture, which should be treated, in case of massive infestation, with a suitable insecticide at the start 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 should be taken. Specific precautions to be taken by the person administering the veterinary medicinal product to animals: This veterinary medicinal product may cause eye, skin, and mucous membrane irritation. 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 all contact with the veterinary medicinal product. Avoid contact of the veterinary medicinal product with your fingers. If this occurs, wash your hands with soap and water. After accidental eye exposure, rinse the eye gently with water. Wash your 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. Therefore, it is recommended that animals not be treated during the day, but rather at dusk, and that recently treated animals not sleep with their owners, especially children. Use during pregnancy and breastfeeding: Cats : Can be used during pregnancy. Ferrets : The safety of this product has not been established in ferrets during pregnancy and lactation. Use only according to the benefit/risk assessment performed by the responsible veterinarian. Storage method Do not store above 30°C. Store in the original packaging. Observations Non-prescription veterinary medicine.