SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Pestigon 50 mg Spot-On Solution for Cats 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One 0.5 ml pipette contains: Active Fipronil Excipients Butylhydroxyanisole E320 Butylhydroxytoluene E321 50 mg 0.1 mg 0.05 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, colourless to pale yellow solution. 4. CLINICAL PARTICULARS 4.1 Target Species Cats. 4.2 Indications for Use, Specifying the Target Species For the treatment of infestations by fleas (Ctenocephalides felis). The product shows immediate insecticidal effect and persistent insecticidal activity against new infestations by adult fleas for up to 5 weeks. The product shows acaricidal efficacy with killing effect against ticks (Ixodes ricinus) within 48 hours. The product has persistent acaricidal efficacy for up to 2 weeks against ticks (Dermacentor reticulatus). If ticks of this species are present when the product is applied, all ticks will not be killed within the first 48 hours but they may be killed within a week. The product can be used as part of a treatment programme for Flea Allergy Dermatitis where this has been previously diagnosed by a Veterinary Surgeon. Page 1 of 71
4.3 Contra-Indications In the absence of available data, the product should not be used on kittens less than 8 weeks old and/or weighing less than 1 kg. Do not use on sick (systemic diseases, fever ) or convalescent animals. Do not use in rabbits, as adverse drug reactions and even death could occur. Do not use in cases of known hypersensitivity to the active substance or to any of the excipients. 4.4 Special Warnings for Each Target Species The product does not prevent ticks from attaching to the animals. If the animal has been treated prior to exposure to the ticks, the ticks will start to be killed in the first 24-48 hours after attachment. This will usually be prior to engorgement, minimising but not excluding the risk of transmission of diseases. Once dead ticks will often drop off the animal but any remaining ticks may be easily removed by a gentle pull. When used as part of a strategy for the treatment of Flea Allergy Dermatitis, monthly applications to the allergic patient and to other cats in the household are recommended. For optimum control of flea problems in a multi-pet household, all dogs and cats in the household should be treated with a suitable insecticide. Avoid frequent swimming or shampooing of the animal because the maintenance of effectiveness of the product in these cases has not been tested. Fleas from pets often infest the animal s basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. 4.5 Special Precautions for Use (i) Special precautions for use in animals Avoid contact with the animal s eyes. In the case of accidental eye contact immediately and thoroughly flush the eyes with water. It is important to make sure that the product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. Do not apply the product to wounds or damaged skin. Page 2 of 71
(ii) Special precautions to be taken by the person administering the veterinary medicinal product to the animals This product can cause mucous membrane and eye irritation. contact of the product with mouth and eyes should be avoided. Therefore, In case of accidental eye contact, immediately and thoroughly rinse eyes with plain water. If irritation to the eyes persists contact your doctor immediately and bring with you the package leaflet. Avoid contents coming into contact with the fingers. hands with soap and water. If this occurs, wash Wash hands after use. Do not smoke, drink or eat during application. People with a known hypersensitivity to fipronil or excipients (see section 6.1) should avoid contact with the veterinary medicinal product. Treated animals should not be handled until this application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals should not be allowed to sleep with owners, especially children. Keep pipettes in original packaging and dispose of used pipettes immediately. (iii) Other precautions The alcohol carrier may have adverse effects on painted, varnished or other household surfaces or furnishings This product is flammable. Keep away from heat, sparks, open flame or other sources of ignition. 4.6 Adverse reactions (frequency and seriousness) If licking occurs, a brief period of hypersalivation may be observed due mainly to the nature of the carrier. Among the extremely rare suspected adverse reactions, transient cutaneous reactions at the application site (scaling, local alopecia, pruritus, erythema) and general pruritus or alopecia have been reported after use. Exceptionally, hypersalivation, reversible neurological signs (hyperaesthesia, depression, nervous signs) or vomiting have been observed after use. The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals displaying adverse reactions during the course of one treatment) - common (more than 1 but less than 10 animals in 100 animals) Page 3 of 71
- uncommon (more than 1 but less than 10 animals in 1,000 animals) - rare (more than 1 but less than 10 animals in 10,000 animals) - very rare (less than 1 animal in 10,000 animals, including isolated reports). 4.7 Use During Pregnancy, Lactation or Lay Laboratory studies using fipronil have not shown any evidence of teratogenic or embryotoxic effects. Studies have not been carried out with this product in pregnant and lactating animals. Use in pregnancy and lactation only in accordance with professional veterinary advice and a benefit/risk assessment. 4.8 Interaction with Other Medicinal Products and Other Forms of Interaction None known. 4.9 Amounts to be Administered and Administration Route For external use only. Animals should be weighed accurately prior to treatment. Route of administration: By topical application to the skin. Dosage: 1 pipette of 0.5 ml per cat (approximately 7.5 15 mg/kg). Method of Administration: Hold upright. Tap the narrow part of the pipette to ensure the contents are within the main body of the pipette. Break back the snap-off top from the spot-on pipette along the scored line. Part the coat between the shoulder blades until the skin is visible. Place the tip of the pipette on the skin and squeeze gently to empty its contents onto the skin, preferably at two spots, one at the base of the skull and a second 2-3 cms further back. Page 4 of 71
It is important to ensure that the product is applied to an area where the animal cannot lick it off, and to make sure that animals do not lick each other following treatment. Care should be taken to avoid excessive wetting of the hair with the product since this will cause a sticky appearance of hairs at the treatment spot. However, should this occur, it will disappear within 24 hours post application. For optimal control of flea and/or tick infestation the treatment schedule can be based on the local epidemiological situation. In the absence of safety studies, the minimum treatment interval is 4 weeks. 4.10 Overdose (Symptoms, Emergency Procedures, Antidotes), if Necessary The toxicity of the product administered to the skin is very low. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal Periods Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Ectoparasiticides for topical use. ATCvet code: QP53AX15 5.1 Pharmacodynamic Properties Fipronil is an insecticide/acaricide in the phenylpyrazole family. It acts by inhibiting the GABA complex, binding to the chloride channel and thereby blocking pre- and post-synaptic transfer of chloride ions across the membrane. This results in uncontrolled activity of the central nervous system and death in insects and acarids. Fipronil exhibits insecticidal activity against fleas (Ctenocephalides felis), and acaricidal activity against ticks (Dermacentor reticulatus) in the cat. Newly arriving fleas are killed within 24 hours of landing on the animal. The product is effective against flea infestation for approximately 5 weeks and against tick (Dermacentor reticulatus) infestations for 2 weeks, depending on the level of challenge. 5.2 Pharmacokinetic Properties Fipronil is mainly metabolised to its sulfone derivative (RM1602), which also possesses insecticidal and acaricidal properties. Page 5 of 71
After a local application of fipronil to the cat, systemic absorption is negligible. The concentrations of fipronil on the hair decrease with time. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Povidone K12 Polysorbate 80 Butyl Alcohol Diethylene Glycol Monoethyl Ether 6.2 Incompatibilities None known. 6.3 Shelf-Life Shelf life of the veterinary medicinal product as packaged for sale: 3 years 6.4 Special Precautions for Storage This medicinal product does not require any special temperature storage conditions. Store in the original container in order to protect from light and moisture. 6.5 Nature and Composition of Immediate Packaging 0.5 ml pipette, moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4-ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes Not all pack sizes may be marketed. 6.6 Special Precautions for the Disposal of Unused Veterinary Medicinal Product or Waste Materials Derived from the Use of Such Products. Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. Fipronil may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container. Page 6 of 71
7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4324 9. DATE OF FIRST AUTHORISATION 03 July 2012 10. DATE OF REVISION OF THE TEXT May 2017 Approved: 08 May 2017 Page 7 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Pestigon 67 mg Spot-On Solution for Small Dogs 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One 0.67 ml pipette contains: Active substance: Fipronil Excipients: Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) 67 mg 0.134 mg 0.067 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, colourless to pale yellow solution. 4. CLINICAL PARTICULARS 4.1 Target Species Dogs. 4.2 Indications for Use, Specifying the Target Species For the treatment of infestations by fleas (Ctenocephalides felis). The product shows immediate insecticidal effect and persistent insecticidal activity against new infestations by adult fleas for up to 8 weeks. The product has a persistent acaricidal efficacy against Ixodes ricinus for up to 2 weeks, Rhipicephalus sanguineus for up to 3 weeks and Dermacentor reticulatus for up to 4 weeks. If ticks of these species are present when the product is applied, all ticks will not be killed within the first 48 hours but they may be killed within a week. The product can be used as part of a treatment programme for Flea Allergy Dermatitis where this has been previously diagnosed by a Veterinary Surgeon. 4.3 Contra-Indications Do not use in dogs weighing less than 2 kg. Page 8 of 71
In the absence of available data, the product should not be used in puppies less than 8 weeks old. Do not use in sick (systemic diseases, fever ) or convalescent animals. Do not use in rabbits, as adverse reactions and even death could occur. This product is specifically developed for dogs. Do not use in cats, as this could lead to overdosing. Do not use in cases of known hypersensitivity to the active or to any of the excipients. 4.4 Special Warnings for Each Target Species The product does not prevent ticks from attaching to the animals, but ticks may be killed in the first 24-48 hours after attachment prior to full engorgement and therefore minimising the risk of transmission of diseases. Once dead, ticks will often drop off the animal, but any remaining ticks may easily be removed by a gentle pull. When used as part of a strategy for the treatment of Flea Allergy Dermatitis, monthly applications to the allergic patient and to other dogs in the household are recommended. For optimal control of flea infestation in multi-pet household, all dogs and cats in the house should be treated with a suitable insecticide. Fleas from pets often infest the animal s basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. Avoid frequent swimming or shampooing of the animal because the maintenance of effectiveness of the product in these cases has not been tested. 4.5 Special Precautions for Use (i) Special precautions for use in animals Avoid contact with the animal s eyes. In the case of accidental eye contact immediately and thoroughly flush the eyes with water. It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that animals do not lick each other following treatment. Do not apply the product on wounds or damaged skin. Page 9 of 71
(ii) Special precautions to be taken by the person administering the veterinary medicinal product to the animals This product can cause mucous membrane and eye irritation. Therefore, contact of the product with the mouth and eyes should be avoided. In cases of accidental eye contact, immediately and thoroughly rinse the eye with plain water. If eye irritation persists seek medical advice and show the package leaflet or the label to a physician. People with a known hypersensitivity to fipronil or excipients (section 6.1) should avoid contact with the veterinary product. Avoid contents coming into contact with the fingers. hands with soap and water. If this occurs, wash Wash hands after use. Do not smoke, drink or eat during application. Treated animals should not be handled until this application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals should not be allowed to sleep with owners, especially children. Keep pipettes in original packaging and dispose of used pipettes immediately. (iii) Other precautions Fipronil may adversely affect aquatic organisms. Dogs should not be allowed to swim in watercourses for 2 days after application. The alcohol carrier may have adverse effect on painted, varnished or other household surfaces or furnishings. This product is flammable. Keep away from heat, sparks, open flame or other sources of ignition. 4.6 Adverse reactions (frequency and seriousness) If licking occurs, a brief period of hypersalivation may be observed due mainly to the nature of the carrier. Among the extremely rare suspected adverse reactions, transient cutaneous reactions at the application site (skin discoloration, local alopecia, pruritus, erythema) and general pruritus or alopecia have been reported after use. Exceptionally, hypersalivation, reversible neurological signs (hyperaesthesia, depression, nervous signs), vomiting or respiratory signs have been observed after use. The frequency of adverse reactions is defined using the following convention: Page 10 of 71
- very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of one treatment) - common (more than 1 but less than 10 animals in 100 animals) - uncommon (more than 1 but less than 10 animals in 1,000 animals) - rare (more than 1 but less than 10 animals in 10,000 animals) - very rare (less than 1 animal in 10,000 animals, including isolated reports). 4.7 Use During Pregnancy, Lactation or Lay Laboratory studies using fipronil have not shown any evidence of teratogenic or embryotoxic effects. Studies have not been carried out with this product in pregnant and lactating animals. Use in pregnancy and lactation only in accordance with professional veterinary advice and a benefit/risk assessment. 4.8 Interaction with Other Medicinal Products and Other Forms of Interaction None known. 4.9 Amounts to be Administered and Administration Route Route of administration: By topical application to the skin. For external use only. Apply the product directly to the skin based on weight of the animal. Animals should be weighed accurately prior to treatment. Dosage 1 pipette of 0.67 ml per dog weighing over 2 kg and up to 10 kg bodyweight. Method of Administration: Hold upright. Tap the narrow part of the pipette to ensure the contents are within the main body of the pipette. Break back the snap-off top from the spot-on pipette along the scored line. Part the coat between the shoulder blades until the skin is visible. Place the tip of the pipette on the skin and squeeze gently at one or two spots to empty its contents onto the skin. Page 11 of 71
It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that the animals do not lick each other following treatment. Care should be taken to avoid excessive wetting of the hair with the product since this will cause a sticky appearance of hairs at the treatment spot. However, should this occur, it will disappear within 48 hours post application. For the optimal control of infestation by flea and or/tick the treatment schedule can be based on local epidemiological situation. In the absence of safety studies, the minimum treatment interval is 4 weeks. 4.10 Overdose (Symptoms, Emergency Procedures, Antidotes), if Necessary No adverse effects were observed in target animal safety studies in 8 week old puppies, growing dogs and dogs weighing circa 2kg treated on 3 occasions at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal Periods Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Ectoparasiticides for topical use. ATC Vet Code: QP53AX15 5.1 Pharmacodynamic Properties Fipronil is an insecticide/acaricide in the phenylpyrazole family. It acts by inhibiting the GABA complex, binding to the chloride channel and thereby blocking pre- and post-synaptic transfer of chloride ions across the cell membrane. This results in uncontrolled activity of the central nervous system and death in insects and acarids. Fipronil exhibits insecticidal activity against fleas (Ctenocephalides felis), and acaricidal activity against ticks (Rhipicephalus sanguineus, Dermacentor reticulatus, Ixodes ricinus) in the dog. Newly arriving fleas are killed within 24 hours of landing on the animal. Ticks if already present at the time of application of the product, may not always be killed in the first 48 hours, however will be killed within 9 days post treatment. The product is effective against flea infestation (Ctenocephalides felis) for approximately 8 weeks and against tick infestations for up to 4 weeks (see indications for use), depending on the tick species and the level of challenge. Page 12 of 71
5.2 Pharmacokinetic Particulars After a local application of fipronil to the dog, it is slightly absorbed through the skin. Low levels of fipronil may be detected in the plasma, with a very high variability between dogs. After application, there is a good distribution of the chemical on the hair, presenting a good gradient of concentration between the application zone and the peripheral area. Fipronil is mainly metabolised to its sulfone derivative (RM1602), which also possesses insecticidal and acaricidal properties. The concentrations of fipronil on the hair decrease with time. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Povidone K12 Polysorbate 80 Butyl Alcohol Diethylene Glycol Monoethyl Ether 6.2 Incompatibilities None known. 6.3 Shelf-Life Shelf life of the veterinary medicinal product as packaged for sale: 3 years 6.4 Special Precautions for Storage This medicinal product does not require any special temperature storage conditions. Store in the original container in order to protect from light and moisture. 6.5 Nature and Composition of Immediate Packaging 0.67 ml pipette, moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4-ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes Not all pack sizes may be marketed. Page 13 of 71
6.6 Special Precautions for the Disposal of Unused Veterinary Medicinal Product or Waste Materials Derived from the Use of Such Products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. Fipronil may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Newry Co. Down BT35 6JP United Kingdom 8. MARKETING AUTHORISATION NUMBER Vm 02000/4325 9. DATE OF FIRST AUTHORISATION 04 July 2012 10. DATE OF REVISION OF THE TEXT June 2017 Approved: 14 June 2017 Page 14 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Pestigon 134 mg Spot-On Solution for Medium Dogs 3. QUALITATIVE AND QUANTITATIVE COMPOSITION One 1.34 ml pipette contains: Active substance: Fipronil Excipients: Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) 134 mg 0.268 mg 0.134 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, colourless to pale yellow solution. 4. CLINICAL PARTICULARS 4.1 Target Species Dogs. 4.2 Indications for Use, Specifying the Target Species For the treatment of infestations by fleas (Ctenocephalides felis). The product shows immediate insecticidal effect and persistent insecticidal activity against new infestations by adult fleas for up to 8 weeks. The product has a persistent acaricidal efficacy against Ixodes ricinus for up to 2 weeks, Rhipicephalus sanguineus for up to 3 weeks and Dermacentor reticulatus for up to 4 weeks. If ticks of these species are present when the product is applied, all ticks will not be killed within the first 48 hours but they may be killed within a week. The product can be used as part of a treatment programme for Flea Allergy Dermatitis where this has been previously diagnosed by a Veterinary Surgeon. 4.3 Contra-Indications Page 15 of 71
Do not use in dogs weighing less than 10 kg. In the absence of available data, the product should not be used in puppies less than 8 weeks old. Do not use in sick (systemic diseases, fever ) or convalescent animals. Do not use in rabbits, as adverse reactions and even death could occur. This product is specifically developed for dogs. Do not use in cats, as this could lead to overdosing. Do not use in cases of known hypersensitivity to the active or to any of the excipients. 4.4 Special Warnings for Each Target Species The product does not prevent ticks from attaching to the animals, but ticks may be killed in the first 24-48 hours after attachment prior to full engorgement and therefore minimising the risk of transmission of diseases. Once dead, ticks will often drop off the animal, but any remaining ticks may easily be removed by a gentle pull. When used as part of a strategy for the treatment of Flea Allergy Dermatitis, monthly applications to the allergic patient and to other dogs in the household are recommended. For optimal control of flea infestation in multi-pet household, all dogs and cats in the house should be treated with a suitable insecticide. Fleas from pets often infest the animal s basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. Avoid frequent swimming or shampooing of the animal because the maintenance of effectiveness of the product in these cases has not been tested. 4.5 Special Precautions for Use (i) Special precautions for use in animals Avoid contact with the animal s eyes.in the case of accidental eye contact immediately and thoroughly flush the eyes with water. It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that animals do not lick each other following treatment. Page 16 of 71
Do not apply the product on wounds or damaged skin. (ii) Special precautions to be taken by the person administering the veterinary medicinal product to the animals This product can cause mucous membrane and eye irritation. Therefore, contact of the product with the mouth and eyes should be avoided. In cases of accidental eye contact, immediately and thoroughly rinse the eye with plain water. If eye irritation persists seek medical advice and show the package leaflet or the label to a physician. People with a known hypersensitivity to fipronil or excipients (section 6.1) should avoid contact with the veterinary product. Avoid contents coming into contact with the fingers. hands with soap and water. If this occurs, wash Wash hands after use. Do not smoke, drink or eat during application. Treated animals should not be handled until this application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals should not be allowed to sleep with owners, especially children. Keep pipettes in original packaging and dispose of used pipettes immediately. (iii) Other precautions Fipronil may adversely affect aquatic organisms. Dogs should not be allowed to swim in watercourses for 2 days after application. The alcohol carrier may have adverse effect on painted, varnished or other household surfaces or furnishings. This product is flammable. Keep away from heat, sparks, open flame or other sources of ignition. 4.6 Adverse reactions (frequency and seriousness) If licking occurs, a brief period of hypersalivation may be observed due mainly to the nature of the carrier. Among the extremely rare suspected adverse reactions, transient cutaneous reactions at the application site (skin discoloration, local alopecia, pruritus, erythema) and general pruritus or alopecia have been reported after use. Exceptionally, hypersalivation, reversible neurological signs (hyperaesthesia, depression, nervous signs), vomiting or respiratory signs have been observed after use. Page 17 of 71
The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of one treatment) - common (more than 1 but less than 10 animals in 100 animals) - uncommon (more than 1 but less than 10 animals in 1,000 animals) - rare (more than 1 but less than 10 animals in 10,000 animals) - very rare (less than 1 animal in 10,000 animals, including isolated reports). 4.7 Use During Pregnancy, Lactation or Lay Laboratory studies using fipronil have not shown any evidence of teratogenic or embryotoxic effects. Studies have not been carried out with this product in pregnant and lactating animals. Use in pregnancy and lactation only in accordance with professional veterinary advice and a benefit/risk assessment. 4.8 Interaction with Other Medicinal Products and Other Forms of Interaction None known. 4.9 Amounts to be Administered and Administration Route Route of administration: By topical application to the skin. For external use only. Apply the product directly to the skin based on weight of the animal. Animals should be weighed accurately prior to treatment. Dosage 1 pipette of 1.34 ml per dog weighing over 10 kg and up to 20 kg bodyweight. Method of Administration: Hold upright. Tap the narrow part of the pipette to ensure the contents are within the main body of the pipette. Break back the snap-off top from the spot-on pipette along the scored line. Part the coat between the shoulder blades until the skin is visible. Place the tip of the pipette on the skin and squeeze gently at one or two spots to empty its contents onto the skin. Page 18 of 71
It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that the animals do not lick each other following treatment. Care should be taken to avoid excessive wetting of the hair with the product since this will cause a sticky appearance of hairs at the treatment spot. However, should this occur, it will disappear within 48 hours post application. For the optimal control of infestation by flea and or/tick the treatment schedule can be based on local epidemiological situation. In the absence of safety studies, the minimum treatment interval is 4 weeks. 4.10 Overdose (Symptoms, Emergency Procedures, Antidotes), if Necessary No adverse effects were observed in target animal safety studies in 8 week old puppies, growing dogs and dogs weighing circa 2kg treated on 3 occasions at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal Periods Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Ectoparasiticides for topical use. ATC Vet Code: QP53AX15 5.1 Pharmacodynamic Properties Fipronil is an insecticide/acaricide in the phenylpyrazole family. It acts by inhibiting the GABA complex, binding to the chloride channel and thereby blocking pre- and post-synaptic transfer of chloride ions across the cell membrane. This results in uncontrolled activity of the central nervous system and death in insects and acarids. Fipronil exhibits insecticidal activity against fleas (Ctenocephalides felis), and acaricidal activity against ticks (Rhipicephalus sanguineus,dermacentor reticulatus, Ixodes ricinus) in the dog. Newly arriving fleas are killed within 24 hours of landing on the animal. Ticks if already present at the time of application of the product, may not always be killed in the first 48 hours, however will be killed within 9 days post treatment. Page 19 of 71
The product is effective against flea infestation (Ctenocephalides felis) for approximately 8 weeks and against tick infestations for up to 4 weeks (see indications for use), depending on the tick species and the level of challenge. 5.2 Pharmacokinetic Particulars After a local application of fipronil to the dog, it is slightly absorbed through the skin. Low levels of fipronil may be detected in the plasma, with a very high variability between dogs. After application, there is a good distribution of the chemical on the hair, presenting a good gradient of concentration between the application zone and the peripheral area. Fipronil is mainly metabolised to its sulfone derivative (RM1602), which also possesses insecticidal and acaricidal properties. The concentrations of fipronil on the hair decrease with time. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Povidone K12 Polysorbate 80 Butyl Alcohol Diethylene Glycol Monoethyl Ether 6.2 Incompatibilities None known. 6.3 Shelf-Life Shelf life of the veterinary medicinal product as packaged for sale: 3 years 6.4 Special Precautions for Storage This medicinal product does not require any special temperature storage conditions. Store in the original container in order to protect from light and moisture. 6.5 Nature and Composition of Immediate Packaging 1.34 ml, pipette moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within Page 20 of 71
a child resistant 4-ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes Not all pack sizes may be marketed. 6.6 Special Precautions for the Disposal of Unused Veterinary Medicinal Product or Waste Materials Derived from the Use of Such Products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. Fipronil may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4326 9. DATE OF FIRST AUTHORISATION 06 July 2012 10. DATE OF REVISION OF THE TEXT June 2017 Approved 13 July 2017 Page 21 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Pestigon 268 mg Spot-On Solution for Large Dogs 4. QUALITATIVE AND QUANTITATIVE COMPOSITION One 2.68 ml pipette contains: Active substance: Fipronil Excipients: Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) 268 mg 0.536 mg 0.268 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, colourless to pale yellow solution. 4. CLINICAL PARTICULARS 4.1 Target Species Dogs. 4.2 Indications for Use, Specifying the Target Species For the treatment of infestations by fleas (Ctenocephalides felis). The product shows immediate insecticidal effect and persistent insecticidal activity against new infestations by adult fleas for up to 8 weeks. The product has a persistent acaricidal efficacy against Ixodes ricinus for up to 2 weeks, Rhipicephalus sanguineus for up to 3 weeks and Dermacentor reticulatus for up to 4 weeks. If ticks of these species are present when the product is applied, all ticks will not be killed within the first 48 hours but they may be killed within a week. The product can be used as part of a treatment programme for Flea Allergy Dermatitis where this has been previously diagnosed by a Veterinary Surgeon. Page 22 of 71
4.3 Contra-Indications Do not use in dogs weighing less than 20 kg. In the absence of available data, the product should not be used in puppies less than 8 weeks old. Do not use in sick (systemic diseases, fever ) or convalescent animals. Do not use in rabbits, as adverse reactions and even death could occur. This product is specifically developed for dogs. Do not use in cats, as this could lead to overdosing. Do not use in cases of known hypersensitivity to the active or to any of the excipients. 4.4 Special Warnings for Each Target Species The product does not prevent ticks from attaching to the animals, but ticks may be killed in the first 24-48 hours after attachment prior to full engorgement and therefore minimising the risk of transmission of diseases. Once dead, ticks will often drop off the animal, but any remaining ticks may easily be removed by a gentle pull. When used as part of a strategy for the treatment of Flea Allergy Dermatitis, monthly applications to the allergic patient and to other dogs in the household are recommended. For optimal control of flea infestation in multi-pet household, all dogs and cats in the house should be treated with a suitable insecticide. Fleas from pets often infest the animal s basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. Avoid frequent swimming or shampooing of the animal because the maintenance of effectiveness of the product in these cases has not been tested. 4.5 Special Precautions for Use (i) Special precautions for use in animals Avoid contact with the animal s eyes. In the case of accidental eye contact immediately and thoroughly flush the eyes with water. It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that animals do not lick each other following treatment. Page 23 of 71
Do not apply the product on wounds or damaged skin. (ii) Special precautions to be taken by the person administering the veterinary medicinal product to the animals This product can cause mucous membrane and eye irritation. Therefore, contact of the product with the mouth and eyes should be avoided. In cases of accidental eye contact, immediately and thoroughly rinse the eye with plain water. If eye irritation persists seek medical advice and show the package leaflet or the label to a physician. People with a known hypersensitivity to fipronil or excipients (section 6.1) should avoid contact with the veterinary product. Avoid contents coming into contact with the fingers. hands with soap and water. If this occurs, wash Wash hands after use. Do not smoke, drink or eat during application. Treated animals should not be handled until this application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals should not be allowed to sleep with owners, especially children. Keep pipettes in original packaging and dispose of used pipettes immediately. (iii) Other precautions Fipronil may adversely affect aquatic organisms. Dogs should not be allowed to swim in watercourses for 2 days after application. The alcohol carrier may have adverse effect on painted, varnished or other household surfaces or furnishings. This product is flammable. Keep away from heat, sparks, open flame or other sources of ignition. 4.6 Adverse reactions (frequency and seriousness) If licking occurs, a brief period of hypersalivation may be observed due mainly to the nature of the carrier. Among the extremely rare suspected adverse reactions, transient cutaneous reactions at the application site (skin discoloration, local alopecia, pruritus, erythema) and general pruritus or alopecia have been reported after use. Exceptionally, hypersalivation, reversible neurological signs (hyperaesthesia, depression, nervous signs), vomiting or respiratory signs have been observed after use. Page 24 of 71
The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of one treatment) - common (more than 1 but less than 10 animals in 100 animals) - uncommon (more than 1 but less than 10 animals in 1,000 animals) - rare (more than 1 but less than 10 animals in 10,000 animals) - very rare (less than 1 animal in 10,000 animals, including isolated reports). 4.7 Use During Pregnancy, Lactation or Lay Laboratory studies using fipronil have not shown any evidence of teratogenic or embryotoxic effects. Studies have not been carried out with this product in pregnant and lactating animals. Use in pregnancy and lactation only in accordance with professional veterinary advice and a benefit/risk assessment. 4.8 Interaction with Other Medicinal Products and Other Forms of Interaction None known. 4.9 Amounts to be Administered and Administration Route Route of administration: By topical application to the skin. For external use only. Apply the product directly to the skin based on weight of the animal. Animals should be weighed accurately prior to treatment. Dosage 1 pipette of 2.68 ml per dog weighing over 20 kg and up to 40 kg bodyweight. For dogs over 60 kg use two pipettes of 2.68 ml. Method of Administration: Hold upright. Tap the narrow part of the pipette to ensure the contents are within the main body of the pipette. Break back the snap-off top from the spot-on pipette along the scored line. Part the coat between the shoulder blades until the skin is visible. Place the tip of the pipette on the skin and squeeze gently at one or two spots to empty its contents onto the skin. Page 25 of 71
It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that the animals do not lick each other following treatment. Care should be taken to avoid excessive wetting of the hair with the product since this will cause a sticky appearance of hairs at the treatment spot. However, should this occur, it will disappear within 48 hours post application. For the optimal control of infestation by flea and or/tick the treatment schedule can be based on local epidemiological situation. In the absence of safety studies, the minimum treatment interval is 4 weeks. 4.10 Overdose (Symptoms, Emergency Procedures, Antidotes), if Necessary No adverse effects were observed in target animal safety studies in 8 week old puppies, growing dogs and dogs weighing circa 2kg treated on 3 occasions at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal Periods Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Ectoparasiticides for topical use. ATC Vet Code: QP53AX15 5.1 Pharmacodynamic Properties Fipronil is an insecticide/acaricide in the phenylpyrazole family. It acts by inhibiting the GABA complex, binding to the chloride channel and thereby blocking pre- and post-synaptic transfer of chloride ions across the cell membrane. This results in uncontrolled activity of the central nervous system and death in insects and acarids. Fipronil exhibits insecticidal activity against fleas (Ctenocephalides felis), and acaricidal activity against ticks (Rhipicephalus sanguineus, Dermacentor reticulatus, Ixodes ricinus) in the dog. Newly arriving fleas are killed within 24 hours of landing on the animal. Ticks if already present at the time of application of the product, may not always be killed in the first 48 hours, however will be killed within 9 days post treatment. The product is effective against flea infestation (Ctenocephalides felis) for approximately 8 weeks and against tick infestations for up to 4 weeks (see indications for use), depending on the tick species and the level of challenge. Page 26 of 71
5.2 Pharmacokinetic Particulars After a local application of fipronil to the dog, it is slightly absorbed through the skin. Low levels of fipronil may be detected in the plasma, with a very high variability between dogs. After application, there is a good distribution of the chemical on the hair, presenting a good gradient of concentration between the application zone and the peripheral area. Fipronil is mainly metabolised to its sulfone derivative (RM1602), which also possesses insecticidal and acaricidal properties. The concentrations of fipronil on the hair decrease with time. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Povidone K12 Polysorbate 80 Butyl Alcohol Diethylene Glycol Monoethyl Ether 6.2 Incompatibilities None known. 6.3 Shelf-Life Shelf life of the veterinary medicinal product as packaged for sale: 3 years 6.4 Special Precautions for Storage This medicinal product does not require any special temperature storage conditions. Store in the original container in order to protect from light and moisture. 6.5 Nature and Composition of Immediate Packaging 2.68 ml, pipette moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4-ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes Not all pack sizes may be marketed. Page 27 of 71
6.6 Special Precautions for the Disposal of Unused Veterinary Medicinal Product or Waste Materials Derived from the Use of Such Products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. Fipronil may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4327 9. DATE OF FIRST AUTHORISATION 06 July 2012 10. DATE OF REVISION OF THE TEXT June 2017 Approved 13 June 2017 Page 28 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Pestigon 402 mg Spot-On Solution for Very Large Dogs 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One 4.02 ml pipette contains Active substance: Fipronil Excipients: Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) 402 mg 0.804 mg 0.402 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, colourless to pale yellow solution. 4. CLINICAL PARTICULARS 4.1 Target Species Dogs. 4.2 Indications for Use, Specifying the Target Species For the treatment of infestations by fleas (Ctenocephalides felis). The product shows immediate insecticidal effect and persistent insecticidal activity against new infestations by adult fleas for up to 8 weeks. The product has a persistent acaricidal efficacy against Ixodes ricinus for up to 2 weeks, Rhipicephalus sanguineus for up to 3 weeks and Dermacentor reticulatus for up to 4 weeks. If ticks of these species are present when the product is applied, all ticks will not be killed within the first 48 hours but they may be killed within a week. The product can be used as part of a treatment programme for Flea Allergy Dermatitis where this has been previously diagnosed by a Veterinary Surgeon. 4.3 Contra-Indications Do not use in dogs weighing less than 40 kg. In the absence of available data, the product should not be used in puppies less than 8 weeks old. Page 29 of 71
Do not use in sick (systemic diseases, fever ) or convalescent animals. Do not use in rabbits, as adverse reactions and even death could occur. This product is specifically developed for dogs. Do not use in cats, as this could lead to overdosing. Do not use in cases of known hypersensitivity to the active or to any of the excipients. 4.4 Special Warnings for Each Target Species The product does not prevent ticks from attaching to the animals, but ticks may be killed in the first 24-48 hours after attachment prior to full engorgement and therefore minimising the risk of transmission of diseases. Once dead, ticks will often drop off the animal, but any remaining ticks may easily be removed by a gentle pull. When used as part of a strategy for the treatment of Flea Allergy Dermatitis, monthly applications to the allergic patient and to other dogs in the household are recommended. For optimal control of flea infestation in multi-pet household, all dogs and cats in the house should be treated with a suitable insecticide. Fleas from pets often infest the animal s basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. Avoid frequent swimming or shampooing of the animal because the maintenance of effectiveness of the product in these cases has not been tested. 4.5 Special Precautions for Use (i) Special precautions for use in animals Avoid contact with the animal s eyes.in the case of accidental eye contact immediately and thoroughly flush the eyes with water. It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that animals do not lick each other following treatment. Do not apply the product on wounds or damaged skin. Page 30 of 71
(ii) Special precautions to be taken by the person administering the veterinary medicinal product to the animals This product can cause mucous membrane and eye irritation. Therefore, contact of the product with the mouth and eyes should be avoided. In cases of accidental eye contact, immediately and thoroughly rinse the eye with plain water. If eye irritation persists seek medical advice and show the package leaflet or the label to a physician. People with a known hypersensitivity to fipronil or excipients (section 6.1) should avoid contact with the veterinary product. Avoid contents coming into contact with the fingers. hands with soap and water. If this occurs, wash Wash hands after use. Do not smoke, drink or eat during application. Treated animals should not be handled until this application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals should not be allowed to sleep with owners, especially children. Keep pipettes in original packaging and dispose of used pipettes immediately. (iii) Other precautions Fipronil may adversely affect aquatic organisms. Dogs should not be allowed to swim in watercourses for 2 days after application. The alcohol carrier may have adverse effect on painted, varnished or other household surfaces or furnishings. This product is flammable. Keep away from heat, sparks, open flame or other sources of ignition. 4.6 Adverse reactions (frequency and seriousness) If licking occurs, a brief period of hypersalivation may be observed due mainly to the nature of the carrier. Among the extremely rare suspected adverse reactions, transient cutaneous reactions at the application site (skin discoloration, local alopecia, pruritus, erythema) and general pruritus or alopecia have been reported after use. Exceptionally, hypersalivation, reversible neurological signs (hyperaesthesia, depression, nervous signs), vomiting or respiratory signs have been observed after use. Page 31 of 71
The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of one treatment) - common (more than 1 but less than 10 animals in 100 animals) - uncommon (more than 1 but less than 10 animals in 1,000 animals) - rare (more than 1 but less than 10 animals in 10,000 animals) - very rare (less than 1 animal in 10,000 animals, including isolated reports). 4.7 Use During Pregnancy, Lactation or Lay Laboratory studies using fipronil have not shown any evidence of teratogenic or embryotoxic effects. Studies have not been carried out with this product in pregnant and lactating animals. Use in pregnancy and lactation only in accordance with professional veterinary advice and a benefit/risk assessment. 4.8 Interaction with Other Medicinal Products and Other Forms of Interaction None known. 4.9 Amounts to be Administered and Administration Route Route of administration: By topical application to the skin. For external use only. Apply the product directly to the skin based on weight of the animal. Animals should be weighed accurately prior to treatment. Dosage 1 pipette of 4.02 ml per dog weighing over 40 kg and up to 60 kg bodyweight. For dogs over 60 kg use two pipettes of 2.68 ml. Method of Administration: Hold upright. Tap the narrow part of the pipette to ensure the contents are within the main body of the pipette. Break back the snap-off top from the spot-on pipette along the scored line. Part the coat between the shoulder blades until the skin is visible. Place the tip of the pipette on the skin and squeeze gently at one or two spots to empty its contents onto the skin. Page 32 of 71
It is important to make sure that the product is applied to an area where the animal cannot lick it off, and to make sure that the animals do not lick each other following treatment. Care should be taken to avoid excessive wetting of the hair with the product since this will cause a sticky appearance of hairs at the treatment spot. However, should this occur, it will disappear within 48 hours post application. For the optimal control of infestation by flea and or/tick the treatment schedule can be based on local epidemiological situation. In the absence of safety studies, the minimum treatment interval is 4 weeks. 4.10 Overdose (Symptoms, Emergency Procedures, Antidotes), if Necessary No adverse effects were observed in target animal safety studies in 8 week old puppies, growing dogs and dogs weighing circa 2kg treated on 3 occasions at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal Periods Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Ectoparasiticides for topical use. ATC Vet Code: QP53AX15 5.1 Pharmacodynamic Properties Fipronil is an insecticide/acaricide in the phenylpyrazole family. It acts by inhibiting the GABA complex, binding to the chloride channel and thereby blocking pre- and post-synaptic transfer of chloride ions across the cell Page 33 of 71
Page 34 of 71 membrane. This results in uncontrolled activity of the central nervous system and death in insects and acarids. Fipronil exhibits insecticidal activity against fleas (Ctenocephalides felis), and acaricidal activity against ticks (Rhipicephalus sanguineus, Dermacentor reticulatus, Ixodes ricinus) in the dog. Newly arriving fleas are killed within 24 hours of landing on the animal. Ticks if already present at the time of application of the product, may not always be killed in the first 48 hours, however will be killed within 9 days post treatment. The product is effective against flea infestation (Ctenocephalides felis) for approximately 8 weeks and against tick infestations for up to 4 weeks (see indications for use), depending on the tick species and the level of challenge. 5.2 Pharmacokinetic Particulars After a local application of fipronil to the dog, it is slightly absorbed through the skin. Low levels of fipronil may be detected in the plasma, with a very high variability between dogs. After application, there is a good distribution of the chemical on the hair, presenting a good gradient of concentration between the application zone and the peripheral area. Fipronil is mainly metabolised to its sulfone derivative (RM1602), which also possesses insecticidal and acaricidal properties. The concentrations of fipronil on the hair decrease with time. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Povidone K12 Polysorbate 80 Butyl Alcohol Diethylene Glycol Monoethyl Ether 6.2 Incompatibilities None known. 6.3 Shelf-Life Shelf life of the veterinary medicinal product as packaged for sale: 3 years 6.4 Special Precautions for Storage This medicinal product does not require any special temperature storage conditions.
Store in the original container in order to protect from light and moisture. 6.5 Nature and Composition of Immediate Packaging 4.02 ml, pipette moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4-ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes Not all pack sizes may be marketed. 6.6 Special Precautions for the Disposal of Unused Veterinary Medicinal Product or Waste Materials Derived from the Use of Such Products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. Fipronil may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty container. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited, Station Works, Newry, Co. Down, BT35 6JP, United Kingdom 8. MARKETING AUTHORISATION NUMBER Vm 02000/4328 9. DATE OF FIRST AUTHORISATION 06 July 2012 10. DATE OF REVISION OF THE TEXT June 2017 Approved: 14 June 2017 Page 35 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT PestiGon Combo 50 mg / 60 mg spot-on solution for cats and ferrets (IE, BG, FR, HR, CY, CZ, EE, EL, HU, IT, LV, LT, MT, PT, RO, SK, ES, UK) Bolfo Combo 50 mg / 60 mg spot-on solution for cats and ferrets (DE) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each pipette of 0.5 ml contains: Active substances: Fipronil... 50 mg (S)-methoprene... 60 mg Excipients: Butylhydroxyanisole (E320)... 0.10 mg Butylhydroxytoluene (E321)... 0.05 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, yellow solution. 4. CLINICAL PARTICULARS 4.1 Target species Cats and ferrets. 4.2 Indications for use, specifying the target species In cats: To be used against infestations with fleas, alone or in association with ticks and/or biting lice. Elimination of fleas (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 4 weeks. Prevention of the multiplication of fleas by inhibiting the development of eggs (ovicidal activity), 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). The product has a persistent acaricidal efficacy for up to 2 weeks against ticks (based on experimental data). Elimination of biting lice (Felicola subrostratus). The product can be used as part of a treatment strategy for the control of Flea Allergy Dermatitis (FAD). Page 36 of 71
In ferrets: To be used against infestations with fleas, alone or in association with ticks. Elimination of fleas (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 4 weeks. Prevention of the multiplication of fleas by inhibiting the development of eggs (ovicidal activity), larvae and pupae (larvicidal activity) originating from eggs laid by adult fleas. Elimination of ticks (Ixodes ricinus). The product has a persistent acaricidal efficacy for 4 weeks against ticks (based on experimental data). 4.3 Contraindications In the absence of available data, the product should not be used on kittens less than 8 weeks old and/or weighing less than 1 kg. The product should not be used on ferrets less than 6 months old. Do not use on sick (e.g. systemic diseases, fever) or convalescent animals. Do not use in rabbits, as adverse drug reactions with even mortality could occur. In absence of studies, the use of the product is not recommended in non-target species. Do not use in cases of hypersensitivity to the active substances or to any of the excipients. 4.4 Special warnings for each target species Avoid contact with the animal s eyes. 4.5 Special precautions for use Special precautions for use in animals It is important to make sure that the product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. No data on the effect of bathing/shampooing on the efficacy of the product in cats and ferrets are available. However, based on information available for dogs shampooed as from 2 days after application of the product, it is not recommended to bath animals within 2 days after application of the product. There may be an attachment of single ticks. For this reason a transmission of infectious diseases cannot be completely excluded if conditions are unfavourable. Fleas from pets often infest the animal s basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. The potential toxicity of the product for kittens of less than 8 weeks of age in contact with a treated queen is not documented. Special care should be taken in this case. Page 37 of 71
Special precautions to be taken by the person administering the veterinary medicinal product to animals This product can cause mucous membrane, skin and eye irritation. Therefore, contact of the product with mouth, skin and eyes should be avoided. In case of accidental eye contact, immediately and thoroughly rinse the eyes with clean water. If eye irritation persists seek medical advice and show the package leaflet or the label to the physician. If contact with the skin occurs, wash hands with soap and water. People with a known hypersensitivity to insecticides or alcohol should avoid contact with the veterinary medicinal product. Wash hands after use. Ingestion of the product is harmful. Prevent children getting access to the pipettes and discard the used pipettes immediately after applying the product. In case of accidental ingestion of product, seek medical advice immediately. Treated animals should not be handled until the application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals are not allowed to sleep with owners, especially children. 4.6 Adverse reactions (frequency and seriousness) Do not overdose. Cats: Among the very rare suspected adverse reactions, transient skin reactions on the application site (scaling, local hair loss, itching, redness) and general itching or hair loss have been reported after use. Excessive salivation, reversible nervous signs (increased sensitivity to stimulation, depression, other nervous signs) or vomiting have also been observed after use. The frequency of adverse reactions is defined using the following convention: - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). If licking occurs, a brief period of excessive salivation may be observed due mainly to the nature of the carrier. 4.7 Use during pregnancy, lactation or lay Cats: The product can be used during pregnancy. For treatment during the lactating period, see section 4.5 i). Ferrets: Page 38 of 71
Laboratory studies in cats have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. The safety of the veterinary medicinal product has not been established in ferrets during pregnancy and lactation. Use only according to the risk-benefit assessment by the responsible veterinarian. 4.8 Interaction with other medicinal products and other forms of interaction None known. 4.9 Amounts to be administered and administration route Dosage: One pipette of 0.5 ml per cat, corresponding to a minimum recommended dose of 5 mg/kg for fipronil and 6 mg/kg for (S)-methoprene. In the absence of safety studies, the minimum treatment interval is 4 weeks. One pipette of 0.5 ml per ferret corresponding to a dose of 50 mg for fipronil and 60 mg for (S)-methoprene per ferret. The minimum treatment interval is 4 weeks. Route of administration: External use only, spot-on use.. Only remove pipette from sachet immediately prior to use. Method of Administration: Remove the pipette from the outer sachet using scissors or fold along diagonal line to expose nick; tear back at nick. Hold the pipette upright. Tap the narrow part of the pipette to ensure the contents remain within the main body of the pipette. Twist or snap back the tip. Part the coat on the back of the animal 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 Page 39 of 71
pipette several times to empty its contents completely and directly onto the skin in one spot. Temporary changes to the coat (clumped/greasy hair) may be noted at the application site. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary The risk of experiencing adverse effects may increase with overdosing (see section 4.6). In cats: No undesirable effects were observed in target animal safety studies in cats and kittens aged 8 weeks and older and weighing about 1 kg treated once a month at five times the recommended dose for six consecutive months. Itching may occur following treatment. Overdose application of the product will cause a sticky appearance of hairs at the treatment spot. However, should this occur, it will disappear within 24 hours post application. In ferrets: In ferrets aged 6 months and older and treated once every 2 weeks for four treatments, at five times the recommended dose, body weight loss was observed in some animals. 4.11 Withdrawal period(s) Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Ectoparasiticides for topical use, fipronil combinations. ATCvet code: QP53AX65 5.1 Pharmacodynamic properties Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of insects or acarines. Fipronil kills fleas within 24 hours, ticks (Dermacentor variabilis, Rhipicephalus sanguineus, Ixodes scapularis, Ixodes ricinus, Haemaphysalis longicornis, Page 40 of 71
Page 41 of 71 Haemaphysalis flava, Haemaphysalis campanulata) and lice within 48 hours postexposure. (S)-Methoprene is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues that inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes impaired development and death of the developing stages of fleas. The on-animal ovicidal activity of (S)-methoprene results from either direct penetration of the eggshell of newly laid eggs or from absorption through the cuticle of the adult fleas. (S)-methoprene is also effective in preventing flea larvae and pupae from developing, which prevents contamination of the environment of treated animals with the immature stages of fleas. 5.2 Pharmacokinetic particulars Studies of metabolism of fipronil have demonstrated that the major metabolite is the sulfone derivative of fipronil. (S)-methoprene is extensively degraded into carbon dioxide and acetate that are subsequently incorporated into endogenous materials. The pharmacokinetic profiles after topical application of fipronil and (S)-methoprene in combination were studied in cats in comparison to intravenous dosing of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters under conditions mimicking clinical practice. The topical application, with additional potential oral exposure from licking, resulted in overall systemic absorption of fipronil (18%) with a mean maximum concentration (Cmax) of approximately 100 ng/ml fipronil and 13 ng/ml of fipronil sulfone in plasma. Peak fipronil plasma concentrations are rapidly attained (mean tmax approximately 6 h) and decline with a mean terminal half-life of approximately 25 h. Fipronil is slightly metabolised to fipronil sulfone in cats. Plasma concentrations of (S)-methoprene were generally below the limit of quantitation (20 ng/ml) in cats after topical application. Both (S)-methoprene and fipronil, together with its major metabolite, are welldistributed in the haircoat of cats within one day after application. The concentrations of fipronil, fipronil sulfone and (S)-methoprene in the hair coat decrease with time and are detectable for at least 59 days after dosing. Parasites are killed through contact rather than by systemic exposure. No pharmacological interaction between fipronil and (S)-methoprene was noted. The pharmacokinetic profile of the product has not been investigated in ferrets. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Ethanol anhydrous Polysorbate 80 Povidone K17
Diethylene glycol monoethyl ether 6.2 Major incompatibilities None known. 6.3 Shelf life Shelf life of the veterinary medicinal product as packaged for sale: 2 years 6.4 Special precautions for storage Store in the original package in order to protect from light and moisture. This veterinary medicinal product does not require any special temperature storage conditions. 6.5 Nature and composition of immediate packaging 0.5 ml pipette, moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4- ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12 or 24 pipettes. Each pipette is individually sealed in a foil sachet. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. Fipronil and (S)-methoprene may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty containers. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4417 Page 42 of 71
9. DATE OF FIRST AUTHORISATION 16 May 2017 10. DATE OF REVISION OF THE TEXT January 2018 PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. Approved: 19 January 2018 Page 43 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT PestiGon Combo 67 mg / 60.3 mg spot-on solution for small dogs (IE, BG, FR, HR, CY, CZ, EE, EL, HU, IT, LV, LT, MT, PT, RO, SK, ES, UK) Bolfo Combo 67 mg / 60.3 mg spot-on solution for small dogs (DE) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each pipette of 0.67 ml contains: Active substances: Fipronil... 67 mg (S)-methoprene... 60.3 mg Excipients: Butylhydroxyanisole (E320)... 0.13 mg Butylhydroxytoluene (E321)... 0.07 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, yellow solution 4. CLINICAL PARTICULARS 4.1 Target species Dogs. 4.2 Indications for use, specifying the target species For the treatment of dogs weighing 2 to 10 kg bodyweight. To be used against infestations with fleas, alone or in association with ticks and/or biting lice. Treatment of flea infestations (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persist for 8 weeks. Prevention of the multiplication of fleas by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) originating from eggs laid by adult fleas for eight weeks after application. Treatment of tick infestations (Ixodes ricinus, Dermacentor variabilis, Dermacentor reticulatus, Rhipicephalus sanguineus). The product has a persistent acaricidal efficacy for up to 4 weeks against ticks. Treatment of infestations with biting lice (Trichodectes canis). Page 44 of 71
Page 45 of 71 The product can be used as part of a treatment strategy for the control of Flea Allergy Dermatitis (FAD). 4.3 Contraindications In the absence of available data, the product should not be used on puppies less than 8 weeks old and/or weighing less than 2 kg. Do not use on sick (e.g. systemic diseases, fever) or convalescent animals. Do not use in rabbits, as adverse reactions with even mortality could occur. In the absence of studies, the use of the product is not recommended in non-target species. This product is specifically developed for dogs. Do not use in cats and ferrets, as this could lead to overdosing. Do not use in cases of hypersensitivity to the active substances or to any of the excipients. 4.4 Special warnings for each target species Bathing/immersion in water within 2 days after application of the product and more frequent bathing than once a week should be avoided, as no study has been performed to investigate how this affects the efficacy of the product. Emollient shampoos can be used prior to treatment, but reduce the duration of protection against fleas to approximately 5 weeks when used weekly after application of the product. Weekly bathing with a 2% chlorhexidine medicated shampoo did not affect efficacy against fleas during a 6 week long study. Dogs should not be allowed to swim in watercourses for 2 days after application (See section 6.6) There may be an attachment of a few ticks. For this reason a transmission of infectious diseases cannot be completely excluded if conditions are unfavorable. Fleas from pets often infest the animal's basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. 4.5 Special precautions for use Special precautions for use in animals Avoid contact with the animal s eyes. It is important to make sure that the product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. Special precautions to be taken by the person administering the veterinary medicinal product to animals This product can cause mucous membrane, skin and eye irritation. Therefore, contact of the product with mouth, skin and eyes should be avoided. In case of accidental eye contact, immediately and thoroughly rinse the eyes with clean water. If eye irritation persists seek medical advice and show the package leaflet or the label to the physician. If contact with the skin occurs, wash hands with soap and water. People with a known hypersensitivity to insecticides or alcohol should avoid contact with the veterinary medicinal product.
Wash hands after use. Ingestion of the product is harmful. Prevent children getting access to the pipettes and discard the used pipettes immediately after applying the product. In case of accidental ingestion of product, seek medical advice immediately. Treated animals should not be handled until the application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals are not allowed to sleep with owners, especially children. 4.6 Adverse reactions (frequency and seriousness) Among the very rare suspected adverse reactions, transient skin reactions on the application site (skin discoloration, local hair loss, itching, redness) and general itching or hair loss have been reported after use. Excessive salivation, reversible nervous signs (increased sensitivity to stimulation, depression, other nervous signs), vomiting or respiratory symptoms have also been observed after use. The frequency of adverse reactions is defined using the following convention: - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). If licking occurs, a brief period of excessive salivation may be observed due mainly to the nature of the carrier. Do not overdose. 4.7 Use during pregnancy, lactation or lay The product can be used during pregnancy and lactation. 4.8 Interaction with other medicinal products and other forms of interaction None known. 4.9 Amounts to be administered and administration route Dosage: One pipette of 0.67 ml per dog weighing over 2 and up to 10 kg, corresponding to a minimum recommended dose of 6.7 mg/kg for fipronil and 6 mg/kg for (S)-methoprene. In the absence of safety studies, the minimum treatment interval is 4 weeks. Route of administration: External use only, spot-on use. Only remove pipette from sachet immediately prior to use. Method of Administration: Page 46 of 71
Remove the pipette from the outer sachet using scissors or fold along diagonal line to expose nick; tear back at nick. Hold the pipette upright. Tap the narrow part of the pipette to ensure the contents remain within the main body of the pipette. Twist or snap back the tip. Part the coat on the back of the animal 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 to empty its contents completely and directly onto the skin in one spot. Temporary changes to the coat (clumped/greasy hair) may be noted at the application site. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary No adverse effects were observed in target animal safety studies in 8 week-old puppies, growing dogs and dogs weighing about 2 kg treated once at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal period(s) Not applicable. Page 47 of 71
5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Ectoparasiticides for topical use, fipronil combinations. ATCvet code: QP53AX65 5.1 Pharmacodynamic properties Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and postsynaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of insects or acarines. 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 lice within 48 hours post-exposure. (S)-Methoprene is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues that inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes impaired development and death of the developing stages of fleas. The on-animal ovicidal activity of (S)-methoprene results from either direct penetration of the eggshell of newly laid eggs or from absorption through the cuticle of the adult fleas. (S)-methoprene is also effective in preventing flea larvae and pupae from developing, which prevents contamination of the environment of treated animals with the immature stages of fleas. 5.2 Pharmacokinetic particulars Studies of metabolism of fipronil have demonstrated that the major metabolite is the sulfone derivative of fipronil. (S)-methoprene is extensively degraded into carbon dioxide and acetate that are subsequently incorporated into endogenous materials. The pharmacokinetic profiles after topical application of fipronil and (S)-methoprene in combination were studied in dogs in comparison to intravenous dosing of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters. The topical application resulted in low systemic absorption of fipronil (11%) with a mean maximum concentration (Cmax) of approximately 35 ng/ml fipronil and 55 ng/ml of fipronil sulfone in plasma. Peak fipronil plasma concentrations are slowly attained (mean tmax approximately 101 h), and decline slowly (mean terminal half-life approximately 154 h, highest values are observed for males). Fipronil is extensively metabolised to fipronil sulfone after topical administration. Plasma concentrations of (S)-methoprene were below the limit of quantitation (20 ng/ml) in dogs after topical application. Both (S)-methoprene and fipronil, together with its major metabolite, are welldistributed in the haircoat of a dog within one day after application. The concentrations of fipronil, fipronil sulfone and S-methoprene in the hair coat decrease with time and are detectable for at least 60 days after dosing. Parasites are killed through contact rather than systemic exposure. Page 48 of 71
No pharmacological interaction between fipronil and (S)-methoprene was noted. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Ethanol anhydrous Polysorbate 80 Povidone K17 Diethylene glycol monoethyl ether 6.2 Major incompatibilities None known. 6.3 Shelf life Shelf life of the veterinary medicinal product as packaged for sale: 2 years 6.4. Special precautions for storage Store in the original package in order to protect from light and moisture. This veterinary medicinal product does not require any special temperature storage conditions. 6.5 Nature and composition of immediate packaging 0.67 ml pipette, moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4- ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12 or 24 pipettes. Each pipette is individually sealed in a foil sachet. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. Fipronil and (S)-methoprene may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty containers. Page 49 of 71
7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4418 9. DATE OF FIRST AUTHORISATION 16 May 2017 10. DATE OF REVISION OF THE TEXT January 2018 PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. Approved: 19 January 2018 Page 50 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT PestiGon Combo 134 mg / 120.6 mg spot-on solution for medium dogs (IE, BG, FR, HR, CY, CZ, EE, EL, HU, IT, LV, LT, MT, PT, RO, SK, ES, UK) Bolfo Combo 134 mg / 120.6 mg spot-on solution for medium dogs (DE) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each pipette of 1.34 ml contains: Active substances: Fipronil... 134 mg (S)-methoprene... 120.6 mg Excipients: Butylhydroxyanisole (E320)... 0.27 mg Butylhydroxytoluene (E321)... 0.13 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, yellow solution. 4. CLINICAL PARTICULARS 4.1 Target species Dogs. 4.2 Indications for use, specifying the target species For the treatment of dogs weighing 10 to 20 kg bodyweight: To be used against infestations with fleas, alone or in association with ticks and/or biting lice. Treatment of flea infestations (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 8 weeks. Prevention of the multiplication of fleas by inhibiting of the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) originating from eggs laid by adult fleas for eight weeks after application. Treatment of tick infestations (Ixodes ricinus, Dermacentor variabilis, Dermacentor reticulatus, Rhipicephalus sanguineus). The product has a persistent acaricidal efficacy for up to 4 weeks against ticks. Treatment of infestations with biting lice (Trichodectes canis). Page 51 of 71
Page 52 of 71 The product can be used as part of a treatment strategy for the control of Flea Allergy Dermatitis (FAD). 4.3 Contraindications In the absence of available data, the product should not be used on puppies less than 8 weeks old. Do not use on sick (e.g. systemic diseases, fever) or convalescent animals. Do not use in rabbits, as adverse reactions with even mortality could occur. In absence of studies, the use of the product is not recommended in non-target species. This product is specifically developed for dogs. Do not use in cats and ferrets, as this could lead to overdosing. Do not use in cases of hypersensitivity to the active substances or to any of the excipients. 4.4 Special warnings for each target species Bathing/immersion in water within 2 days after application of the product and more frequent bathing than once a week should be avoided, as no study has been performed to investigate how this affects the efficacy of the product. Emollient shampoos can be used prior to treatment, but reduce the duration of protection against fleas to approximately 5 weeks when used weekly after application of the product. Weekly bathing with a 2% chlorhexidine medicated shampoo did not affect efficacy against fleas during a 6 week long study. Dogs should not be allowed to swim in watercourses for 2 days after application (see section 6.6). There may be an attachment of a few ticks. For this reason a transmission of infectious diseases cannot be completely excluded if conditions are unfavourable. Fleas from pets often infest the animal's basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. 4.5 Special precautions for use Special precautions for use in animals Avoid contact with the animal s eyes. It is important to make sure that the product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. Special precautions to be taken by the person administering the veterinary medicinal product to animals This product can cause mucous membrane, skin and eye irritation. Therefore, contact of the product with mouth, skin and eyes should be avoided. In case of accidental eye contact, immediately and thoroughly rinse the eyes with clean water. If eye irritation persists seek medical advice and show the package leaflet or the label to the physician. If contact with the skin occurs, wash hands with soap and water.
People with a known hypersensitivity to insecticides or alcohol should avoid contact with the veterinary medicinal product. Wash hands after use. Ingestion of the product is harmful. Prevent children getting access to the pipettes and discard the used pipettes immediately after applying the product. In case of accidental ingestion of product, seek medical advice immediately. Treated animals should not be handled until the application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals are not allowed to sleep with owners, especially children. 4.6 Adverse reactions (frequency and seriousness) Among the very rare suspected adverse reactions, transient skin reactions on the application site (skin discoloration, local hair loss, itching,redness) and general itching or hair loss have been reported after use. Excessive salivation, reversible nervous signs (increased sensitivity to stimulation, depression, other nervous signs), vomiting or respiratory symptoms have also been observed after use. The frequency of adverse reactions is defined using the following convention: - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). If licking occurs, a brief period of excessive salivation may be observed due mainly to the nature of the carrier. Do not overdose. 4.7 Use during pregnancy, lactation or lay The product can be used during pregnancy and lactation. 4.8 Interaction with other medicinal products and other forms of interaction None known. 4.9 Amounts to be administered and administration route Dosage: One pipette of 1.34 ml per dog weighing over 10 kg and up to 20 kg, corresponding to a minimum recommended dose of 6.7 mg/kg for fipronil and 6 mg/kg for (S)-methoprene. In the absence of safety studies the minimum treatment interval is 4 weeks. Route of administration: External use only, spot-on use. Only remove pipette from sachet immediately prior to use. Page 53 of 71
Method of Administration: Remove the pipette from the outer sachet using scissors or fold along diagonal line to expose nick; tear back at nick. Hold the pipette upright. Tap the narrow part of the pipette to ensure the contents remain within the main body of the pipette. Twist or snap back the tip. Part the coat on the back of the animal 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 to empty its contents completely and directly onto the skin in one spot. Temporary changes to the coat (clumped/greasy hair) may be noted at the application site. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary No adverse effects were observed in target animal safety studies in 8 week-old puppies, growing dogs and dogs weighing about 2 kg treated once at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal period(s) Not applicable. Page 54 of 71
5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Ectoparasiticides for topical use, fipronil combinations. ATCvet code: QP53AX65 5.1 Pharmacodynamic properties Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and postsynaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of insects or acarines. 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 lice within 48 hours post-exposure. (S)-Methoprene is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues that inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes impaired development and death of the developing stages of fleas. The on-animal ovicidal activity of (S)-methoprene results from either direct penetration of the eggshell of newly laid eggs or from absorption through the cuticle of the adult fleas. (S)-methoprene is also effective in preventing flea larvae and pupae from developing, which prevents contamination of the environment of treated animals with the immature stages of fleas. 5.2 Pharmacokinetic particulars Studies of metabolism of fipronil have demonstrated that the major metabolite is the sulfone derivative of fipronil. (S)-methoprene is extensively degraded into carbon dioxide and acetate that are subsequently incorporated into endogenous materials. The pharmacokinetic profiles after topical application of fipronil and (S)-methoprene in combination were studied in dogs in comparison to intravenous dosing of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters. The topical application resulted in low systemic absorption of fipronil (11%) with a mean maximum concentration (Cmax) of approximately 35 ng/ml fipronil and 55 ng/ml of fipronil sulfone in plasma. Peak fipronil plasma concentrations are slowly attained (mean tmax approximately 101 h), and decline slowly (mean terminal half-life approximately 154 h, highest values are observed for males). Fipronil is extensively metabolised to fipronil sulfone after topical administration. Plasma concentrations of (S)-methoprene were below the limit of quantitation (20 ng/ml) in dogs after topical application. Both (S)-methoprene and fipronil, together with its major metabolite, are welldistributed in the haircoat of a dog within one day after application. The concentrations of fipronil, fipronil sulfone and S-methoprene in the hair coat decrease Page 55 of 71
with time and are detectable for at least 60 days after dosing. Parasites are killed through contact rather than systemic exposure. No pharmacological interaction between fipronil and (S)-methoprene was noted. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Ethanol anhydrous Polysorbate 80 Povidone K17 Diethylene glycol monoethyl ether 6.2 Major incompatibilities None known. 6.3 Shelf life Shelf life of the veterinary medicinal product as packaged for sale: 2 years 6.4 Special precautions for storage Store in the original package in order to protect from light and moisture. This veterinary medicinal product does not require any special temperature storage conditions. 6.5 Nature and composition of immediate packaging 1.34 ml pipette, moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4- ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes. Each pipette is individually sealed in a foil sachet. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. Page 56 of 71
Fipronil and (S)-methoprene may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty containers. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4419 9. DATE OF FIRST AUTHORISATION 16 May 2017 10. DATE OF REVISION OF THE TEXT January 2018 PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. Approved: 19 January 2018 Page 57 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT PestiGon Combo 268 mg / 241.2 mg spot-on solution for large dogs (IE, BG, FR, HR, CY, CZ, EE, DE, EL, HU, IT, LV, LT, MT, PT, RO, SK, ES, UK) Bolfo Combo 268 mg / 241.2 mg spot-on solution for large dogs (DE) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each pipette of 2.68 ml contains: Active substances: Fipronil... 268 mg (S)-methoprene... 241.2 mg Excipients: Butylhydroxyanisole (E320)... 0.54 mg Butylhydroxytoluene (E321)... 0.27 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, yellow solution 4. CLINICAL PARTICULARS 4.1 Target species Dogs 4.2 Indications for use, specifying the target species For the treatment of dogs weighing 20 to 40 kg bodyweight. To be used against infestations with fleas, alone or in association with ticks and/or biting lice. Treatment of flea infestations (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 8 weeks. Prevention of the multiplication of fleas by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) originating from eggs laid by adult fleas for eight weeks after application. Treatment of tick infestations (Ixodes ricinus, Dermacentor variabilis, Dermacentor reticulatus, Rhipicephalus sanguineus). The product has persistent acaricidal efficacy for up to 4 weeks against ticks. Treatment of infestations with biting lice (Trichodectes canis). The product can be used as part of a treatment strategy for the control of Flea Allergy Dermatitis (FAD). Page 58 of 71
4.3 Contraindications In the absence of available data, the product should not be used on puppies less than 8 weeks old. Do not use in rabbits, as adverse reactions with even mortality could occur. In absence of studies, the use of the product is not recommended in non-target species. Do not use on sick (e.g. systemic diseases, fever) or convalescent animals. This product is specifically developed for dogs. Do not use in cats and ferrets, as this could lead to overdosing. Do not use in cases of hypersensitivity to the active substances or to any of the excipients. 4.4 Special warnings for each target species Bathing/immersion in water within 2 days after application of the product and more frequent bathing than once a week should be avoided, as no study has been performed to investigate how this affects the efficacy of the product. Emollient shampoos can be used prior to treatment, but reduce the duration of protection against fleas to approximately 5 weeks when used weekly after application of the product Weekly bathing with a 2% chlorhexidine medicated shampoo did not affect efficacy against fleas during a 6 week long study. Dogs should not be allowed to swim in watercourses for 2 days after application (see section 6.6). There may be an attachment of a few ticks. For this reason a transmission of infectious diseases cannot be completely excluded if conditions are unfavourable. Fleas from pets often infest the animal's basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. 4.5 Special precautions for use Special precautions for use in animals Avoid contact with the animal s eyes. It is important to make sure that the product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. Special precautions to be taken by the person administering the veterinary medicinal product to animals This product can cause mucous membrane, skin and eye irritation. Therefore, contact of the product with mouth, skin and eyes should be avoided. In case of accidental eye contact, immediately and thoroughly rinse the eyes with clean water. If eye irritation persists seek medical advice and show the package leaflet or the label to the physician. If contact with the skin occurs, wash hands with soap and water. People with a known hypersensitivity to insecticides or alcohol should avoid contact with the veterinary medicinal product. Page 59 of 71
Wash hands after use. Ingestion of the product is harmful. Prevent children getting access to the pipettes and discard the used pipettes immediately after applying the product. In case of accidental ingestion of product, seek medical advice immediately. Treated animals should not be handled until the application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals are not allowed to sleep with owners, especially children. 4.6 Adverse reactions (frequency and seriousness) Among the very rare suspected adverse reactions, transient skin reactions on the application site (skin discoloration, local hair loss, itching, redness) and general itching or hair loss have been reported after use. Excessive salivation, reversible nervous signs (increased sensitivity to stimulation, depression, other nervous signs), vomiting or respiratory symptoms have also been observed after use. The frequency of adverse reactions is defined using the following convention: - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). If licking occurs, a brief period of excessive salivation may be observed due mainly to the nature of the carrier. Do not overdose. 4.7 Use during pregnancy, lactation or lay The product can be used during pregnancy and lactation. 4.8 Interaction with other medicinal products and other forms of interaction None known. 4.9 Amounts to be administered and administration route Dosage: one pipette of 2.68 ml per dog weighing over 20 kg and up to 40 kg, corresponding to a minimum recommended dose of 6.7 mg/kg for fipronil and 6 mg/kg for (S)-methoprene. In the absence of safety studies, the minimum treatment interval is 4 weeks. Route of administration: External use only, spot-on use. Only remove pipette from sachet immediately prior to use. Method of Administration: Page 60 of 71
Remove the pipette from the outer sachet using scissors or fold along diagonal line to expose nick; tear back at nick. Hold the pipette upright. Tap the narrow part of the pipette to ensure the contents remain within the main body of the pipette. Twist or snap back the tip. Part the coat on the back of the animal 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 to empty its contents completely and directly onto the skin in one spot. Temporary changes to the coat (clumped/greasy hair) may be noted at the application site. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary No adverse effects were observed in target animal safety studies in 8 week-old puppies, growing dogs and dogs weighing about 2 kg treated once at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal period(s) Not applicable. Page 61 of 71
5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Ectoparasiticides for topical use, fipronil combinations. ATCvet code: QP53AX65 5.1 Pharmacodynamic properties Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and postsynaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of insects or acarines. 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 lice within 48 hours post-exposure. (S)-Methoprene is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues that inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes impaired development and death of the developing stages of fleas. The on-animal ovicidal activity of (S)-methoprene results from either direct penetration of the eggshell of newly laid eggs or from absorption through the cuticle of the adult fleas. (S)-methoprene is also effective in preventing flea larvae and pupae from developing, which prevents contamination of the environment of treated animals with the immature stages of fleas. 5.2 Pharmacokinetic particulars Studies of metabolism of fipronil have demonstrated that the major metabolite is the sulfone derivative of fipronil. (S)-methoprene is extensively degraded into carbon dioxide and acetate that are subsequently incorporated into endogenous materials. The pharmacokinetic profiles after topical application of fipronil and (S)-methoprene in combination were studied in dogs in comparison to intravenous dosing of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters. The topical application resulted in low systemic absorption of fipronil (11%) with a mean maximum concentration (Cmax) of approximately 35 ng/ml fipronil and 55 ng/ml of fipronil sulfone in plasma. Peak fipronil plasma concentrations are slowly attained (mean tmax approximately 101 h), and decline slowly (mean terminal half-life approximately 154 h, highest values are observed for males). Fipronil is extensively metabolised to fipronil sulfone after topical administration. Plasma concentrations of (S)-methoprene were below the limit of quantitation (20 ng/ml) in dogs after topical application. Both (S)-methoprene and fipronil, together with its major metabolite, are welldistributed in the haircoat of a dog within one day after application. The concentrations of fipronil, fipronil sulfone and S-methoprene in the hair coat decrease Page 62 of 71
Page 63 of 71 with time and are detectable for at least 60 days after dosing. Parasites are killed through contact rather than systemic exposure. No pharmacological interaction between fipronil and (S)-methoprene was noted. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Butylhydroxyanisole (E320) Butylhydroxytoluene (E321) Ethanol anhydrous Polysorbate 80 Povidone K17 Diethylene glycol monoethyl ether 6.2 Major incompatibilities None known. 6.3 Shelf life Shelf life of the veterinary medicinal product as packaged for sale: 2 years 6.4 Special precautions for storage Store in the original package in order to protect from light and moisture. This veterinary medicinal product does not require any special temperature storage conditions. 6.5 Nature and composition of immediate packaging 2.68 ml pipette, moulded from a film composed of 3 layers: a polypropylene/coc/polypropylene, solvent free lacquer laminate and a copolymer of polyethylene/evoh/polyethylene. The pipettes are sealed within a child resistant 4- ply foil sachet composed of LDPE/nylon/aluminium foil/polyester film and presented in an outer box. Boxes of 1, 2, 3, 4, 6, 8, 12, 24, 30, 60, 90, 120 or 150 pipettes. Each pipette is individually sealed in a foil sachet. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. Fipronil and (S)-methoprene may adversely affect aquatic organisms. Do not contaminate ponds, waterways or ditches with the product or empty containers.
7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co. Down BT35 6JP Northern Ireland 8. MARKETING AUTHORISATION NUMBER Vm 02000/4420 9. DATE OF FIRST AUTHORISATION 16 May 2017 10. DATE OF REVISION OF THE TEXT January 2018 PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. Approved: 19 January 2018 Page 64 of 71
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT PestiGon Combo 402 mg / 361.8 mg spot-on solution for very large dogs (IE, BG, FR, HR, CY, CZ, EE, DE, EL, HU, IT, LV, LT, MT, PT, RO, SK, ES, UK) Bolfo Combo 402 mg / 361.8 mg spot-on solution for very large dogs (DE) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each pipette of 4.02 ml contains: Active substances: Fipronil... 402 mg (S)-methoprene... 361.8 mg Excipients: Butylhydroxyanisole (E320)... 0.8 mg Butylhydroxytoluene (E321)... 0.4 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Spot-on solution. A clear, yellow solution 4. CLINICAL PARTICULARS 4.1 Target species Dogs 4.2 Indications for use, specifying the target species For the treatment of dogs weighing over 40 kg bodyweight: To be used against infestations with fleas, alone or in association with ticks and/or biting lice. Treatment of flea infestations (Ctenocephalides spp.). Insecticidal efficacy against new infestations with adult fleas persists for 8 weeks. Prevention of the multiplication of fleas by inhibiting the development of eggs (ovicidal activity) and larvae and pupae (larvicidal activity) originating from eggs laid by adult fleas for eight weeks after application. Treatment of tick infestations (Ixodes ricinus, Dermacentor variabilis, Dermacentor reticulatus, Rhipicephalus sanguineus). The product has a persistent acaricidal efficacy for up to 4 weeks against ticks. Treatment of infestations with biting lice (Trichodectes canis). The product can be used as part of a treatment strategy for the control of Flea Allergy Dermatitis (FAD). Page 65 of 71
4.3 Contraindications In the absence of available data, the product should not be used on puppies less than 8 weeks old Do not use in rabbits, as adverse reactions with even mortality could occur. In absence of studies, the use of the product is not recommended in non-target species. Do not use on sick (e.g. systemic diseases, fever) or convalescent animals. This product is specifically developed for dogs. Do not use in cats and ferrets, as this could lead to overdosing. Do not use in cases of hypersensitivity to the active substances or to any of the excipients. 4.4 Special warnings for each target species Bathing/immersion in water within 2 days after application of the product and more frequent bathing than once a week should be avoided, as no study has been performed to investigate how this affects the efficacy of the product. Emollient shampoos can be used prior to treatment, but reduce the duration of protection against fleas to approximately 5 weeks when used weekly after application of the product. Weekly bathing with a 2% chlorhexidine medicated shampoo did not affect efficacy against fleas during a 6 week long study. Dogs should not be allowed to swim in watercourses for 2 days after application (See section 6.6) There may be an attachment of a few ticks. For this reason a transmission of infectious diseases cannot be completely excluded if conditions are unfavorable. Fleas from pets often infest the animal's basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly. 4.5 Special precautions for use Special precautions for use in animals Avoid contact with the animal s eyes. It is important to make sure that the product is applied to an area where the animal cannot lick it off and to make sure that animals do not lick each other following treatment. Special precautions to be taken by the person administering the veterinary medicinal product to animals This product can cause mucous membrane, skin and eye irritation. Therefore, contact of the product with mouth, skin and eyes should be avoided. In case of accidental eye contact, immediately and thoroughly rinse the eyes with clean water. If eye irritation persists seek medical advice and show the package leaflet or the label to the physician. If contact with the skin occurs, wash hands with soap and water. People with a known hypersensitivity to insecticides or alcohol should avoid contact with the veterinary medicinal product. Page 66 of 71
Wash hands after use. Ingestion of the product is harmful. Prevent children getting access to the pipettes and discard the used pipettes immediately after applying the product. In case of accidental ingestion of product, seek medical advice immediately. Treated animals should not be handled until the application site 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 are not treated during the day, but should be treated during the early evening, and that recently treated animals are not allowed to sleep with owners, especially children. 4.6 Adverse reactions (frequency and seriousness) Among the very rare suspected adverse reactions, transient skin reactions on the application site (skin discoloration, local hair loss, itching, redness) and general itching or hair loss have been reported after use. Excessive salivation, reversible nervous signs (increased sensitivity to stimulation, depression, other nervous signs), vomiting or respiratory symptoms have also been observed after use. The frequency of adverse reactions is defined using the following convention: - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). If licking occurs, a brief period of excessive salivation may be observed due mainly to the nature of the carrier. Do not overdose. 4.7 Use during pregnancy, lactation or lay The product can be used during pregnancy and lactation. 4.8 Interaction with other medicinal products and other forms of interaction None known. 4.9 Amounts to be administered and administration route Dosage: one pipette of 4.02 ml per dog weighing over 40 kg, corresponding to a minimum recommended dose of 6.7 mg/kg for fipronil and 6 mg/kg for (S)- methoprene. Route of administration: External use only, spot-on use. Only remove pipette from sachet immediately prior to use. Method of Administration: Remove the pipette from the outer sachet using scissors or fold along diagonal line to expose nick; tear back at nick. Page 67 of 71
Hold the pipette upright. Tap the narrow part of the pipette to ensure the contents remain within the main body of the pipette. Twist or snap back the tip. Part the coat on the back of the animal 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 to empty its contents completely and directly onto the skin in one spot. Temporary changes to the coat (clumped/greasy hair) may be noted at the application site. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary No adverse effects were observed in target animal safety studies in 8 week-old puppies, growing dogs and dogs weighing about 2 kg treated once at five times the recommended dose. The risk of experiencing adverse effects (see section 4.6) may however increase when overdosing, so animals should always be treated with the correct pipette size according to bodyweight. 4.11 Withdrawal period(s) Not applicable. Page 68 of 71