AMFLEE combo 402 mg/361.8 mg spot-on solution for very large dogs Each 4.02 ml pipette contains: Active substance: Fipronil 402 mg S-methoprene 361.8 mg Excipients: Butylhydroxyanisole (E320) 0.80 mg Butylhydroxytoluene (E321) 0.40 mg PHARMACEUTICAL FORM Spot-on solution. Yellow, transparent solution. Target species Dogs over 40 kg. Indications for use, specifying target species Depending on body weight, dogs are divided into weight groups. - treatment of flea infestation or mixed infestations with ticks and/or malophagous lice in dogs. - treatment of flea infestations (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 8 weeks. Prevention of flea multiplication by inhibiting the development of eggs (ovicidal action) and larvae and pupae (larvicidal action) originating from eggs laid by adult fleas persists for 8 weeks after application of the product. - treatment of tick infestations (Ixodes ricinus, Dermacentor variabilis, Dermacentor reticulatus, Rhipicephalus sanguineus). The product has acaricidal efficacy for up to 4 weeks against ticks. - treatment of infestations with mange lice (Trichodectes canis). The product can be used as part of a treatment strategy for the control of flea allergy dermatitis (FAD), previously diagnosed by the veterinarian. Contraindications In the absence of available data, the product should not be administered to puppies less than 8 weeks of age and/or weighing less than 2 kg. Do not administer the product to sick animals (systemic diseases, fever) or to those in convalescence. The product should not be administered to rabbits due to the risk of serious adverse reactions or even death. The product is especially indicated for dogs. Do not administer to cats and ferrets, as overdose may occur. Do not use in case of hypersensitivity to the active substances or to any of the excipients. Special warnings for each target species There is insufficient data on the efficacy of the product after bathing/shampooing animals. Therefore, this practice is not recommended for 2 days after application of the product and more frequently than once a week. Emollient shampoos can be used before treatment, but if used weekly, they reduce the duration of flea protection to approximately 5 weeks. Weekly bathing with a medicated shampoo containing 2% chlorhexidine does not affect the efficacy of the product against fleas, as shown in studies conducted over a 6-week period. Ticks may appear sporadically. Thus, it is impossible to completely rule out infection with diseases under unfavorable conditions. Pet fleas often infest the animals bedding, bedding and regular resting areas, such as carpets and other soft materials, which should be treated, in case of massive infestation and when initiating control measures, with an appropriate insecticide and vacuumed regularly. Special precautions for use Special precautions for use in animals Avoid contact of the product with the eyes of animals. It is important to ensure that the product is applied in a protected area where the animal cannot lick it and animals should be avoided from licking each other after treatment. Special precautions to be taken by the person administering the veterinary medicinal product to animals The product may cause irritation to mucous membranes, skin and eyes. Therefore, avoid contact of the product with the mouth, skin and eyes. People with known hypersensitivity to insecticides or alcohol should avoid contact with the product. Avoid direct hand contact with the product. In case of accidental contact, wash hands with soap and water. In case of accidental contact with eyes, rinse thoroughly with clean water. Wash hands after use. In case of accidental ingestion, seek medical advice immediately and show the product package leaflet or the label. Do not smoke, drink or eat while applying the product. Do not touch treated animals and do not let children play with them until the application site of the product has dried. Therefore, it is not recommended to apply the treatment during the day but in the evening before going to bed, and animals should not be allowed to sleep with their owners, especially children. Other precautions Dogs should not be allowed to swim in watercourses for 2 days after application of the product (see section 6.6). Adverse reactions (frequency and severity) Among the very rare suspected adverse reactions, transient skin reactions at the site of application of the product (hair discoloration and loss, itching and erythema) and general itching or alopecia may be observed. Exceptionally, reversible neurological symptoms (hyperaesthesia, depression, other neurological signs), hypersalivation, vomiting or respiratory symptoms have been observed after use. If animals lick themselves, short-term hypersalivation may occur, mainly due to the excipients. Avoid overdose. Use during pregnancy, lactation or laying The product can be used during pregnancy and lactation. Interactions with other medicinal products or other forms of interaction They dont know each other. Amounts to be administered and route of administration Route of administration and quantities to be administered: For external use only, spot-on application. It is administered by topical application to the skin; one pipette of 4.02 ml (402 mg fipronil + 361.8 mg S-methoprene) for a dog weighing over 40 kg. In this way, a minimum recommended dose of fipronil of 6.7 mg/kg and a dose of S-methoprene of 6 mg/kg are provided by topical application to the skin. In the absence of safety studies, the minimum interval between applications is 4 weeks. Method of administration: 1. Remove a pipette from the packaging. Hold the pipette upright with the tip pointing upwards and unscrew the pipette cap. 2. With the other end of the stopper thus removed, pierce the pipette seal, then remove the cap. 3. Remove the animals hair from the midline between the shoulder blades to make the skin visible. Place the tip of the pipette on the skin and squeeze the tube several times to empty it directly onto the skin, in one spot. Temporary hair changes (clumping/greasy hair) may be observed at the application site. Overdose (symptoms, emergency procedures, antidotes), as appropriate Studies on the safety of the product in puppies up to 8 weeks of age and weighing around 2 kg, treated monthly with doses 5 times higher than the recommended dose, have shown that there are no undesirable effects. The risk of adverse reactions increases with overdose (see section 4.6), therefore always use the pipette with the dose corresponding to the animals weight. Waiting time Thats not the case. Pharmacodynamic properties Fipronil is an insecticide/acaricide of the phenylpyrazole group. It acts directly on arthropods by interacting with ligands of chloride ion channels, especially those regulated by the neurotransmitter gamma-aminobutyric acid (GABA), thus blocking the pre- and postsynaptic transport of chloride ions across cell membranes. This leads to uncoordinated activities of the central nervous system and the death of insects and mites. Fipronil kills fleas within 24 hours, and ticks (Dermacentor reticulatus, Dermacentor variabilis, Rhipicephalus sanguineus, Ixodes scapularis, Ixodes ricinus, Haemaphysalis longicornis, Haemaphysalis flava, Haemaphysalis campanulata) and malophagous lice within 48 hours after exposure. S-Methoprene is an insect growth regulator (IGR) in the class of compounds known as juvenile hormone analogues, which inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes abnormal development and death of fleas at various stages of development. The local ovicidal activity of S-methoprene results either from direct penetration of the membrane of laid eggs or from absorption through the cuticle of adult fleas. S-methoprene is also effective in preventing the development of flea larvae and pupae, preventing contamination of the environment in which treated animals are kept with immature flea stages. Pharmacokinetic features Studies on the metabolism of fipronil have shown that the main metabolite is fipronil sulfonate. S-methoprene is extensively degraded into carbon dioxide and acetate, which are subsequently incorporated into endogenous substances. The pharmacokinetic profiles after topical application of the combination of fipronil and S-methoprene were studied in dogs, compared to intravenous administration of fipronil or S-methoprene alone. Thus, absorption and other pharmacokinetic parameters were determined under conditions similar to clinical practice. Topical application, together with potential additional oral exposure following licking, results in total systemic absorption of fipronil (11%), with mean maximum plasma concentrations (Cmax) of approximately 35 ng/ml fipronil and 55 ng/ml fipronil sulfonate, respectively. Maximum plasma concentrations of fipronil are reached rapidly (mean Tmax values ​​of approximately 101 hours) and decline slowly, with a mean elimination half-life of approximately 154 hours, with maximum values ​​observed in male dogs. After topical application, fipronil is extensively metabolized to fipronil sulfonate. After topical application to dogs, plasma concentrations of S-methoprene were generally below the limit of quantification (20 ng/ml). Both S-methoprene and fipronil, together with its main metabolite, are well distributed in the fur of dogs one day after application. Concentrations of fipronil, fipronil sulfonate and S-methoprene in the fur decrease with time and are detectable for at least 60 days after administration. Parasites are killed by contact rather than systemic exposure. No pharmacological interactions have been observed between fipronil and S-methoprene. List of excipients Butylated hydroxyanisole (E320) Butylated hydroxytoluene (E321) Povidone (K25) Polysorbate 80 Ethanol 96% Diethylene glycol monoethyl ether incompatibility Not known. Product compliance information Product compliance information Product safety Manufacturer information Personal information Product safety information Currently, product safety information is not available. Manufacturer information Currently, manufacturer information is not available. Responsible person information Currently, information about the person responsible is not available. n Presentation type: Pipette Action: Ticks, Fleas, Lice Dog Weight: 40-60 kg Pieces Set: 3 pieces n Quantity: 3 Pipettes