SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT MILBEMAX film-coated tablets for small cats and kittens 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One tablet contains: Active substances: Milbemycin oxime Praziquantel 4 mg 10 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. Oblong shaped, beige to brown, artificial beef flavoured tablet with a score on both sides. One side bears the imprint BC, the other side NA. 4. CLINICAL PARTICULARS 4.1 Target species Cats. 4.2 Indications for use, specifying the target species In cats: treatment of mixed infections by immature and adult cestodes and nematodes of the following species: - Cestodes: Dipylidium caninum Taenia spp. Echinococcus multilocularis - Nematodes: Ancylostoma tubaeforme Toxocara cati Prevention of heartworm disease (Dirofilaria immitis) if concomitant treatment against cestodes is indicated. 4.3 Contraindications Do not use in cats of less than 6 weeks of age and/or weighing less than 0.5 kg. Page 1 of 6
4.4 Special warnings for each target species In order to develop an effective worm control programme local epidemiological information and the risk of exposure of the cat should be taken into account. It is recommended to treat all the animals living in the same household concomitantly. When infection with the cestode D. caninum has been confirmed, concomitant treatment against intermediate hosts, such as fleas and lice, should be discussed with a veterinarian to prevent re-infection. 4.5 Special precautions for use Special precautions for use in animals As per good veterinary practice, animals should be weighed to ensure accurate dosing. Ensure cats and kittens weighing between 0.5 kg and 2 kg receive the appropriate tablet strength (4 mg MBO/10 mg praziquantel) and the appropriate dose (1/2 or 1 tablet) for the corresponding weight band (1/2 tablet for cats weighing 0.5 to 1 kg ; 1 tablet for cats weighing >1 to 2 kg 1 tablet). Echinococcosis represents a hazard for humans. In case of Echinococcosis, specific guidelines on the treatment and follow up and on the safeguard of persons have to be followed. Experts or institutes of parasitology should be consulted. No studies have been performed with severely debilitated cats or individuals with seriously compromised kidney or liver function. The product is not recommended for such animals or only according to a benefit/risk assessment by the responsible veterinarian. Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use. In the event of accidental ingestion of the tablets, particularly by a child, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) In very rare occasions, especially in young cats, hypersensitivity reactions, systemic signs (such as lethargy), neurological signs (such as ataxia and muscle tremors) and/or gastrointestinal signs (such as emesis and diarrhoea) have been observed after administration of the veterinary medicinal product. The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals treated displaying adverse reaction(s)) - common (more than 1 but less than 10 animals in 100 animals treated) - uncommon (more than 1 but less than 10 animals in 1,000 animals treated) - rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). Page 2 of 6
4.7 Use during pregnancy, lactation or lay MILBEMAX can be used in breeding cats including pregnant and lactating queens. 4.8 Interaction with other medicinal products and other forms of interaction The concurrent use of MILBEMAX with selamectin is well tolerated. No interactions were observed when the recommended dose of the macrocyclic lactone selamectin was administered during treatment with MILBEMAX at the recommended dose. Although not recommended, the concomitant use of MILBEMAX with a spot on containing moxidectin and imidacloprid at recommended dose rates following a single application was well tolerated in one laboratory study in 10 kittens. The safety and efficacy of the concurrent use have not been investigated in field studies. In the absence of further studies, caution should be taken in the case of concurrent use of the product with any other macrocyclic lactone. Also, no such studies have been performed with reproducing animals. 4.9 Amounts to be administered and administration route Minimum recommended dose rate: 2 mg of milbemycin oxime and 5 mg of praziquantel per kg are given orally as a single dose. The product should be administered with or after some food. Doing so ensures optimum protection against heartworm disease. Depending on the bodyweight of the cat, the practical dosing is as follows: Weight Tablets 0.5-1 kg ½ tablet > 1-2 kg 1 tablet MILBEMAX can be inserted into a programme for prevention of heartworm disease if at the same time treatment against tapeworms is indicated. MILBEMAX has a duration of heartworm prevention of one month. For prevention of heartworm disease the use of a monosubstance is preferred. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary In case of overdose, in addition to signs observed at the recommended dose (see section 4.6), drooling was observed. This sign will usually disappear spontaneously within a day. 4.11 Withdrawal period(s) Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Antiparasitic products, insecticides and repellants - endectocides ATC vet Code: QP54A B51 (milbemycin oxime, combinations) Page 3 of 6
5.1 Pharmacodynamic properties Milbemycin oxime belongs to the group of macrocyclic lactones, isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. It is active against mites, against larval and adult stages of nematodes as well as against larvae of Dirofilaria immitis. The activity of milbemycin is related to its action on invertebrate neurotransmission: Milbemycin oxime, like avermectins and other milbemycins, increases nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels (related to vertebrate GABAA and glycine receptors). This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite. Praziquantel is an acylated pyrazino-isoquinoline derivative. Praziquantel is active against cestodes and trematodes. It modifies the permeability for calcium (influx of Ca2+) in the membranes of the parasite inducing an imbalance in the membrane structures, leading to membrane depolarisation and almost instantaneous contraction of the musculature (tetany), rapid vacuolization of the syncytial tegument and subsequent tegumental disintegration (blebbing), resulting in easier expulsion from the gastrointestinal tract or death of the parasite. 5.2 Pharmacokinetic particulars In the cat, praziquantel reaches peak plasma concentrations within an hour after oral administration. The half life of elimination is around 3 hours. In the dog, there is rapid hepatic biotransformation, prinicipally to monohydroxylated derivatives. The principal route of elimination in the dog is renal. After oral administration in the cat, milbemycin oxime reaches peak plasma concentrations within 2 hours. The half life of elimination is around 13 hours ( 9 hours). In the rat, metabolism appears to be complete although slow, since unchanged milbemycin oxime has not been found in urine or feces. Main metabolites in the rat are monohydroxylated derivatives, attributable to hepatic biotransformation. In addition to relatively high liver concentrations, there is some concentration in fat, reflecting its lipophilicity. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Core: Cellulose, microcristalline Croscarmellose sodium Povidone Lactose monohydrate Silica, colloidal anhydrous Magnesium stearate Page 4 of 6
Coat: Hypromellose Macrogol Talc Artificial beef flavour 6.2 Major incompatibilities Not applicable. 6.3 Shelf life Shelf-life of the veterinary medicinal product as packaged for sale: 3 years Shelf-life after first opening of the immediate packaging: 6 months 6.4. Special precautions for storage Do not store above 25 C Keep the blister in the outer carton in order to protect from light 6.5 Nature and composition of immediate packaging PVC/PE/PVdC/aluminium blister Available pack sizes: Box with 2 tablets in blister Box with 4 tablets in blister Box with 10 tablets in blister Box with 20 tablets in blister Box with 50 tablets in blister Box with 100 tablets in blister 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. MILBEMAX should not enter water courses as this may be dangerous for fish and other aquatic organisms. 7. MARKETING AUTHORISATION HOLDER Elanco Europe Ltd Lilly House Priestley Road Basingstoke Hampshire RG24 9NL Page 5 of 6
8. MARKETING AUTHORISATION NUMBER Vm 00879/4041 9. DATE OF FIRST AUTHORISATION 17 April 2003 10. DATE OF REVISION OF THE TEXT September 2018 Approved: 27 September 2018 Page 6 of 6
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT MILBEMAX film-coated tablets for cats 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One tablet contains: Active substances: Milbemycin oxime Praziquantel Excipients: Iron oxide (E172) 16 mg 40 mg 0.288 mg For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. Oblong shaped, reddish to reddish brown, artificial beef flavoured tablet with a score on both sides. One side bears the imprint KK, the other side NA. 4. CLINICAL PARTICULARS 4.1 Target species Cats. 4.2 Indications for use, specifying the target species In cats: treatment of mixed infections by immature and adult cestodes and nematodes of the following species: - Cestodes: Dipylidium caninum Taenia spp. Echinococcus multilocularis - Nematodes: Ancylostoma tubaeforme Toxocara cati Prevention of heartworm disease (Dirofilaria immitis) if concomitant treatment against cestodes is indicated. Page 1 of 6
4.3 Contraindications Do not use in cats weighing less than 2 kg. 4.4 Special warnings In order to develop an effective worm control programme local epidemiological information and the risk of exposure of the cat should be taken into account. It is recommended to treat all the animals living in the same household concomitantly. When infection with the cestode D. caninum has been confirmed, concomitant treatment against intermediate hosts, such as fleas and lice, should be discussed with a veterinarian to prevent re-infection. 4.5 Special precautions for use Special precautions for use in animals As per good veterinary practice, animals should be weighed to ensure accurate dosing. Ensure cats and kittens weighing between 0.5 kg and 2 kg receive the appropriate tablet strength (4 mg MBO/10 mg praziquantel) and the appropriate dose (1/2 or 1 tablet) for the corresponding weight band (1/2 tablet for cats weighing 0.5 to 1 kg ; 1 tablet for cats weighing >1 to 2 kg 1 tablet). Echinococcosis represents a hazard for humans. In case of Echinococcosis, specific guidelines on the treatment and follow up and on the safeguard of persons have to be followed. Experts or institutes of parasitology should be consulted. No studies have been performed with severely debilitated cats or individuals with seriously compromised kidney or liver function. The product is not recommended for such animals or only according to a benefit/risk assessment by the responsible veterinarian. Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use. In the event of accidental ingestion of the tablets, particularly by a child, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) In very rare occasions, especially in young cats, hypersensitivity reactions, systemic signs (such as lethargy), neurological signs (such as ataxia and muscle tremors) and/or gastrointestinal signs (such as emesis and diarrhoea) have been observed after administration of the veterinary medicinal product. The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals treated displaying adverse reaction(s)) - common (more than 1 but less than 10 animals in 100 animals treated) - uncommon (more than 1 but less than 10 animals in 1,000 animals treated) Page 2 of 6
- rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). 4.7 Use during pregnancy, lactation or lay MILBEMAX can be used in breeding cats including pregnant and lactating queens. 4.8 Interaction with other medicinal products and other forms of interaction The concurrent use of MILBEMAX with selamectin is well tolerated. No interactions were observed when the recommended dose of the macrocyclic lactone selamectin was administered during treatment with MILBEMAX at the recommended dose. Although not recommended, the concomitant use of MILBEMAX with a spot on containing moxidectin and imidacloprid at recommended dose rates following a single application was well tolerated in one laboratory study in 10 kittens. The safety and efficacy of the concurrent use have not been investigated in field studies. In the absence of further studies, caution should be taken in the case of concurrent use of the product with any other macrocyclic lactone. Also, no such studies have been performed with reproducing animals. 4.9 Amounts to be administered and administration route Minimum recommended dose rate: 2 mg of milbemycin oxime and 5 mg of praziquantel per kg are given orally as a single dose. The product should be administered with or after some food. Doing so ensures optimum protection against heartworm disease. Depending on the bodyweight of the cat, the practical dosing is as follows: Weight Tablets 2-4 kg ½ tablet > 4-8 kg 1 tablet > 8-12 kg 1½ tablets MILBEMAX can be inserted into a programme for prevention of heartworm disease if at the same time treatment against tapeworms is indicated. MILBEMAX has a duration of heartworm prevention of one month. For regular prevention of heartworm disease the use of a monosubstance is preferred. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary In case of overdose, in addition to signs observed at the recommended dose (see section 4.6), drooling was observed. This sign will usually disappear spontaneously within a day. 4.11 Withdrawal period(s) Not applicable. Page 3 of 6
5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Antiparasitic products, insecticides and repellants - endectocides ATC vet Code: QP54A B51 (milbemycin oxime, combinations) 5.1 Pharmacodynamic properties Milbemycin oxime belongs to the group of macrocyclic lactones, isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. It is active against mites, against larval and adult stages of nematodes as well as against larvae of Dirofilaria immitis. The activity of milbemycin is related to its action on invertebrate neurotransmission: Milbemycin oxime, like avermectins and other milbemycins, increases nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels (related to vertebrate GABAA and glycine receptors). This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite. Praziquantel is an acylated pyrazino-isoquinoline derivative. Praziquantel is active against cestodes and trematodes. It modifies the permeability for calcium (influx of Ca2+) in the membranes of the parasite inducing an imbalance in the membrane structures, leading to membrane depolarisation and almost instantaneous contraction of the musculature (tetany), rapid vacuolization of the syncytial tegument and subsequent tegumental disintegration (blebbing), resulting in easier expulsion from the gastrointestinal tract or death of the parasite. 5.2 Pharmacokinetic particulars In the cat, praziquantel reaches peak plasma concentrations within an hour after oral administration. The half life of elimination is around 3 hours. In the dog, there is rapid hepatic biotransformation, prinicipally to monohydroxylated derivatives. The principal route of elimination in the dog is renal. After oral administration in the cat, milbemycin oxime reaches peak plasma concentrations within 2 hours. The half life of elimination is around 13 hours ( 9 hours). In the rat, metabolism appears to be complete although slow, since unchanged milbemycin oxime has not been found in urine or feces. Main metabolites in the rat are monohydroxylated derivatives, attributable to hepatic biotransformation. In addition to relatively high liver concentrations, there is some concentration in fat, reflecting its lipophilicity. Page 4 of 6
6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Core: Cellulose, microcristalline Croscarmellose sodium Povidone Lactose monohydrate Silica, colloidal anhydrous Magnesium stearate Coat: Hypromellose Macrogol Talc Iron oxide red Artificial beef flavour 6.2 Major incompatibilities Not applicable. 6.3 Shelf life Shelf-life of the veterinary medicinal product as packaged for sale: 3 years Shelf-life after first opening of the immediate packaging: 6 months 6.4. Special precautions for storage Do not store above 25 C Keep the blister in the outer carton in order to protect from light 6.5 Nature and composition of immediate packaging PVC/PE/PVdC/aluminium blister Available pack sizes: Box with 2 tablets in blister Box with 4 tablets in blister Box with 10 tablets in blister Box with 20 tablets in blister Box with 50 tablets in blister Box with 100 tablets in blister Not all pack sizes may be marketed Page 5 of 6
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. MILBEMAX should not enter water courses as this may be dangerous for fish and other aquatic organisms. 7. MARKETING AUTHORISATION HOLDER Elanco Europe Ltd Lilly House Priestley Road Basingstoke Hampshire RG24 9NL 8. MARKETING AUTHORISATION NUMBER Vm 00879/4042 9. DATE OF FIRST AUTHORISATION 17 April 2003 10. DATE OF REVISION OF THE TEXT September 2018 Approved: 27 September 2018 Page 6 of 6
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT MILBEMAX tablets for small dogs and puppies 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One tablet contains : Active substances: Milbemycin oxime 2.5 mg Praziquantel 25.0 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet Oblong shaped, white, with a score on both sides. One side bears the imprint AA, the other side NA. 4. CLINICAL PARTICULARS 4.1 Target species Dogs 4.2 Indications for use, specifying the target species In dogs: treatment of mixed infections by adult cestodes and nematodes of the following species susceptible to praziquantel and milbemycin oxime: - Cestodes: Dipylidium caninum Taenia spp. Echinococcus spp. Mesocestoides spp. - Nematodes: Ancylostoma caninum Toxocara canis Toxascaris leonina Trichuris vulpis Crenosoma vulpis (Reduction of the level of infection) Angiostrongylus vasorum (Reduction of the level of infection by immature adult (L5) and adult parasite stages; see specific treatment and prevention disease schedules under section4.9 Amounts to be administered and administration route ) Thelazia callipaeda (see specific treatment schedule under section 4.9 Amounts to be administered and administration route ) Page 1 of 6
The product can also be used in the prevention of heartworm disease (Dirofilaria immitis) if concomitant treatment against cestodes is indicated. 4.3 Contraindications Do not use in puppies of less than 2 weeks of age and/or weighing less than 0.5 kg. Do not use in cases of hypersensitivity to the active substances or to any of the excipients See also section 4.5 "Special precautions for use". 4.4 Special warnings for each target species It is recommended to treat all the animals living in the same household concomitantly. When infection with the cestode D. caninum has been confirmed, concomitant treatment against intermediate hosts, such as fleas and lice, should be discussed with a veterinarian to prevent re-infection. Studies with milbemycin oxime indicate that the margin of safety in certain dogs of Collie or related breeds is less than in other breeds. In these dogs, the recommended dose should be strictly observed. The tolerance of MILBEMAX in young puppies from these breeds has not been investigated. Clinical signs in Collies are similar to those seen in the general dog population when overdosed (see section 4.10). 4.5 Special precautions for use Special precautions for use in animals As per good veterinary practice, animals should be weighed to ensure accurate dosing Treatment of dogs with a high number of circulating microfilariae can sometimes lead to the appearance of hypersensitivity reactions, such as pale mucous membranes, vomiting, trembling, laboured breathing or excessive salivation. These reactions are associated with the release of proteins from dead or dying microfilariae and are not a direct toxic effect of the product. The use in dogs suffering from microfilaremia is thus not recommended. In heartworm risk-areas, or in the case it is known that a dog has been travelling to and from heartworm risk regions, before using MILBEMAX, a veterinary consultation is advised to exclude the presence of any concurrent infestation of Dirofilaria immitis. In the case of a positive diagnosis, adulticidal therapy is indicated before administering MILBEMAX. Echinococcosis represents a hazard for humans. In case of Echinococcosis, specific guidelines on the treatment and follow up and on the safeguard of persons have to be followed. Experts or institutes of parasitology should be consulted. Page 2 of 6
No studies have been performed with severely debilitated dogs or individuals with seriously compromised kidney or liver function. The product is not recommended for such animals or only according to a benefit/risk assessment by the responsible veterinarian. In dogs less than 4 weeks old, tape worm infection is unusual. Treatment of animals less than 4 weeks old with a combination product may therefore not be necessary. Parasite resistance to any particular class of anthelmintic may develop following frequent, repeated use of an anthelmintic of that class Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use. In case of accidental ingestion of the tablets, particularly by a child, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) In very rare occasions, hypersensitivity reactions, systemic signs (such as lethargy), neurological signs (such as muscle tremors and ataxia) and/or gastrointestinal signs (such as emesis, diarrhea, anorexia and drooling) have been observed in dogs after administration of the veterinary medicinal product. The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals treated displaying adverse reaction(s)) - common (more than 1 but less than 10 animals in 100 animals treated) - uncommon (more than 1 but less than 10 animals in 1,000 animals treated) - rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). 4.7 Use during pregnancy, lactation or lay The product may be used in breeding dogs including pregnant and lactating bitches. 4.8 Interaction with other medicinal products and other forms of interaction The concurrent use of MILBEMAX with selamectin is well tolerated. No interactions were observed when the recommended dose of the macrocyclic lactone selamectin was administered during treatment with MILBEMAX at the recommended dose. In the absence of further studies, caution should be taken in the case of concurrent use of MILBEMAX and other macrocyclic lactones. Also, no such studies have been performed with reproducing animals. 4.9 Amounts to be administered and administration route Minimum recommended dose rate: 0.5 mg of milbemycin oxime and 5 mg of praziquantel per kg are given once orally. The product should be administered with or after some food. Depending on the bodyweight of the dog, the practical dosing is as follows: Page 3 of 6
Weight Tablets 0.5-1 kg ½ tablet > 1 5 kg 1 tablet > 5 10 kg 2 tablets In cases when heartworm disease prevention is used and at the same time treatment against tapeworm is required, MILBEMAX can replace the monovalent product for the prevention of heartworm disease. For treatment of Angiostrongylus vasorum infections, milbemycin oxime should be given four times at weekly intervals. It is recommended, where concomitant treatment against cestodes is indicated, to treat once with MILBEMAX and continue with the monovalent product containing milbemycin oxime alone, for the remaining three weekly treatments. In endemic areas administration of the product every four weeks will prevent angiostrongylosis by reducing immature adult (L5) and adult parasite burden, where concomitant treatment against cestodes is indicated. For the treatment of Thelazia callipaeda, milbemycin oxime should be given in 2 treatments, seven days apart. Where concomitant treatment against cestodes is indicated, MILBEMAX can replace the monovalent product containing milbemycin oxime alone. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary No other signs than those observed at the recommended dose have been observed (see section 4.6). 4.11 Withdrawal period(s) Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Endectocides ATC vet Code : QP54A B51 (milbemycin oxime, combinations) 5.1 Pharmacodynamic properties Milbemycin oxime belongs to the group of macrocyclic lactones, isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. It is active against mites, against larval and adult stages of nematodes as well as against larvae of Dirofilaria immitis. The activity of milbemycin is related to its action on invertebrate neurotransmission: Milbemycin oxime, like avermectins and other milbemycins, increases nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels (related to vertebrate GABAA and glycine receptors). This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite. Page 4 of 6
Praziquantel is an acylated pyrazino-isoquinoline derivative. Praziquantel is active against cestodes and trematodes. It modifies the permeability for calcium (influx of Ca2+) in the membranes of the parasite inducing an imbalance in the membrane structures, leading to membrane depolarisation and almost instantaneous contraction of the musculature (tetany), rapid vacuolization of the syncytial tegument and subsequent tegumental disintegration (blebbing), resulting in easier expulsion from the gastrointestinal tract or death of the parasite. 5.2 Pharmacokinetic particulars After oral administration of praziquantel in the dog, peak serum levels of parent are rapidly attained (Tmax approximately 0.5-4 hours) and decline quickly (t1/2 approximately 1.5 hours). There is a substantial hepatic first-pass effect, with very rapid and almost complete hepatic biotransformation, principally to monohydroxylated (also some di- and tri-hydroxylated) derivatives, which are mostly glucuronide and/or sulfate conjugated before excretion. Plasma binding is about 80%. Excretion is fast and complete (about 90% in 2 days); the principal route of elimination is renal. After oral administration of milbemycin oxime in dogs, peak plasma levels occur at about 2-4 hours, and decline with a half-life of the unmetabolised milbemycin oxime of 1-4 days. Bioavailability is about 80%. In the rat, metabolism appears to be complete although slow, since unchanged milbemycin oxime has not been found in urine or feces. Main metabolites in the rat are monohydroxylated derivatives, attributable to hepatic biotransformation. In addition to relatively high liver concentrations, there is some concentration in fat, reflecting its lipophilicity. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Cellulose, microcristalline Croscarmellose sodium Povidone Lactose monohydrate Silica, colloidal anhydrous Magnesium stearate 6.2 Major incompatibilities Not applicable. 6.3 Shelf life Shelf-life of the veterinary medicinal product as packaged for sale: 2 years Shelf-life after first opening of the immediate packaging: 1 month 6.4. Special precautions for storage Do not store above 30 C Page 5 of 6
Keep the blister in the outer carton in order to protect from light 6.5 Nature and composition of immediate packaging PVC/PE/PVdC/aluminium blister Available pack sizes: Box with 2 tablets in blister Box with 4 tablets in blister Box with 10 tablets in blister Box with 20 tablets in blister Box with 50 tablets in blister Box with 100 tablets in blister 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. MILBEMAX should not enter water courses as this may be dangerous for fish and other aquatic organisms 7. MARKETING AUTHORISATION HOLDER Elanco Europe Ltd Lilly House Priestley Road Basingstoke Hampshire RG24 9NL 8. MARKETING AUTHORISATION NUMBER Vm 00879/4039 9. DATE OF FIRST AUTHORISATION 17 April 2003 10. DATE OF REVISION OF THE TEXT September 2018 Approved: 27 September 2018 Page 6 of 6
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT MILBEMAX tablets for dogs 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One tablet contains: Active substances: Milbemycin oxime 12.5 mg Praziquantel 125.0 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet Round shaped, white. One side bears the imprint CCA, the other side NA. 4. CLINICAL PARTICULARS 4.1 Target species Dogs 4.2 Indications for use, specifying the target species In dogs: treatment of mixed infections by adult cestodes and nematodes of the following species susceptible to praziquantel and milbemycin oxime: - Cestodes: Dipylidium caninum Taenia spp. Echinococcus spp. Mesocestoides spp. - Nematodes: Ancylostoma caninum Toxocara canis Toxascaris leonina Trichuris vulpis Crenosoma vulpis (Reduction of the level of infection) Angiostrongylus vasorum (Reduction of the level of infection by immature adult (L5) and adult parasite stages; see specific treatment and prevention disease schedules under SPC point 4.9 Amounts to be administered and administration route ) Thelazia callipaeda (see specific treatment schedule under section 4.9 Amounts to be administered and administration route ) Page 1 of 7
The product can also be used in the prevention of heartworm disease (Dirofilaria immitis) if concomitant treatment against cestodes is indicated. 4.3 Contraindications Do not use in dogs weighing less than 5 kg Do not use in cases of hypersensitivity to the active substances or to any of the excipients See also section 4.5 "Special precautions for use" 4.4 Special warnings for each target species It is recommended to treat all the animals living in the same household concomitantly. When infection with the cestode D. caninum has been confirmed, concomitant treatment against intermediate hosts, such as fleas and lice, should be discussed with a veterinarian to prevent re-infection. Studies with milbemycin oxime indicate that the margin of safety in certain dogs of Collie or related breeds is less than in other breeds. In these dogs, the recommended dose should be strictly observed. The tolerance of MILBEMAX in young puppies from these breeds has not been investigated. Clinical signs in Collies are similar to those seen in the general dog population when overdosed (see section 4.10). 4.5 Special precautions for use Special precautions for use in animals As per good veterinary practice, animals should be weighed to ensure accurate dosing Treatment of dogs with a high number of circulating microfilariae can sometimes lead to the appearance of hypersensitivity reactions, such as pale mucous membranes, vomiting, trembling, laboured breathing or excessive salivation. These reactions are associated with the release of proteins from dead or dying microfilariae and are not a direct toxic effect of the product. The use in dogs suffering from microfilaremia is thus not recommended. In heartworm risk-areas, or in the case it is known that a dog has been travelling to and from heartworm risk regions, before using MILBEMAX, a veterinary consultation is advised to exclude the presence of any concurrent infestation of Dirofilaria immitis. In the case of a positive diagnosis, adulticidal therapy is indicated before administering MILBEMAX. Echinococcosis represents a hazard for humans. In case of Echinococcosis, specific guidelines on the treatment and follow up and on the safeguard of persons have to be followed. Experts or institutes of parasitology should be consulted. Page 2 of 7
No studies have been performed with severely debilitated dogs or individuals with seriously compromised kidney or liver function. The product is not recommended for such animals or only according to a benefit/risk assessment by the responsible veterinarian. In dogs less than 4 weeks old, tape worm infection is unusual. Treatment of animals less than 4 weeks old with a combination product may therefore not be necessary. Parasite resistance to any particular class of anthelmintic may develop following frequent, repeated use of an anthelmintic of that class Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use. In case of accidental ingestion of the tablets, particularly by a child, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) In very rare occasions, hypersensitivity reactions, systemic signs (such as lethargy), neurological signs (such as muscle tremors and ataxia) and/or gastrointestinal signs (such as emesis, diarrhea, anorexia and drooling) have been observed in dogs after administration of the veterinary medicinal product. The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals treated displaying adverse reaction(s)) - common (more than 1 but less than 10 animals in 100 animals treated) - uncommon (more than 1 but less than 10 animals in 1,000 animals treated) - rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). 4.7 Use during pregnancy, lactation or lay The product may be used in breeding dogs including pregnant and lactating bitches. 4.8 Interaction with other medicinal products and other forms of interaction The concurrent use of MILBEMAX with selamectin is well tolerated. No interactions were observed when the recommended dose of the macrocyclic lactone selamectin was administered during treatment with MILBEMAX at the recommended dose. In the absence of further studies, caution should be taken in the case of concurrent use of MILBEMAX and other macrocyclic lactones. Also, no such studies have been performed with reproducing animals. 4.9 Amounts to be administered and administration route Minimum recommended dose rate: 0.5 mg of milbemycin oxime and 5 mg of praziquantel per kg are given once orally. The product should be administered with or after some food. Page 3 of 7
Depending on the bodyweight of the dog, the practical dosing is as follows: Weight Tablets 5 25 kg 1 tablet >25 50 kg 2 tablets >50 75 kg 3 tablets In cases when heartworm disease prevention is used and at the same time treatment against tapeworm is required, MILBEMAX can replace the monovalent product for the prevention of heartworm disease. For treatment of Angiostrongylus vasorum infections, milbemycin oxime should be given four times at weekly intervals. It is recommended, where concomitant treatment against cestodes is indicated, to treat once with MILBEMAX and continue with the monovalent product containing milbemycin oxime alone, for the remaining three weekly treatments. In endemic areas administration of the product every four weeks will prevent angiostrongylosis by reducing immature adult (L5) and adult parasite burden, where concomitant treatment against cestodes is indicated. For the treatment of Thelazia callipaeda, milbemycin oxime should be given in 2 treatments, seven days apart. Where concomitant treatment against cestodes is indicated, MILBEMAX can replace the monovalent product containing milbemycin oxime alone. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary No other signs than those observed at the recommended dose have been observed (see section 4.6). 4.11 Withdrawal period(s) Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Endectocides ATC vet Code : QP54A B51 (milbemycin oxime, combinations) 5.1 Pharmacodynamic properties Milbemycin oxime belongs to the group of macrocyclic lactones, isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. It is active against mites, against larval and adult stages of nematodes as well as against larvae of Dirofilaria immitis. The activity of milbemycin is related to its action on invertebrate neurotransmission: Milbemycin oxime, like avermectins and other milbemycins, increases nematode and Page 4 of 7
insect membrane permeability to chloride ions via glutamate-gated chloride ion channels (related to vertebrate GABAA and glycine receptors). This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite. Praziquantel is an acylated pyrazino-isoquinoline derivative. Praziquantel is active against cestodes and trematodes. It modifies the permeability for calcium (influx of Ca2+) in the membranes of the parasite inducing an imbalance in the membrane structures, leading to membrane depolarisation and almost instantaneous contraction of the musculature (tetany), rapid vacuolization of the syncytial tegument and subsequent tegumental disintegration (blebbing), resulting in easier expulsion from the gastrointestinal tract or death of the parasite. 5.2 Pharmacokinetic particulars After oral administration of praziquantel in the dog, peak serum levels of parent are rapidly attained (Tmax approximately 0.5-4 hours) and decline quickly (t1/2 approximately 1.5 hours). There is a substantial hepatic first-pass effect, with very rapid and almost complete hepatic biotransformation, principally to monohydroxylated (also some di- and tri-hydroxylated) derivatives, which are mostly glucuronide and/or sulfate conjugated before excretion. Plasma binding is about 80%. Excretion is fast and complete (about 90% in 2 days); the principal route of elimination is renal. After oral administration of milbemycin oxime in dogs, peak plasma levels occur at about 2-4 hours, and decline with a half-life of the unmetabolised milbemycin oxime of 1-4 days. Bioavailability is about 80%. In the rat, metabolism appears to be complete although slow, since unchanged milbemycin oxime has not been found in urine or feces. Main metabolites in the rat are monohydroxylated derivatives, attributable to hepatic biotransformation. In addition to relatively high liver concentrations, there is some concentration in fat, reflecting its lipophilicity. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Cellulose, microcristalline Croscarmellose sodium Povidone Lactose monohydrate Silica, colloidal anhydrous Magnesium stearate 6.2 Major incompatibilities Not applicable. Page 5 of 7
6.3 Shelf life Shelf-life of the veterinary medicinal product as packaged for sale: 2 years 6.4. Special precautions for storage Do not store above 30 C Keep the blister in the outer carton in order to protect from light 6.5 Nature and composition of immediate packaging PVC/PE/PVdC/aluminium blister Available pack sizes: Box with 2 tablets in blister Box with 4 tablets in blister Box with 10 tablets in blister Box with 20 tablets in blister Box with 50 tablets in blister Box with 100 tablets in blister 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. MILBEMAX should not enter water courses as this may be dangerous for fish and other aquatic organisms 7. MARKETING AUTHORISATION HOLDER Elanco Europe Ltd Lilly House Priestley Road Basingstoke Hampshire RG24 9NL 8. MARKETING AUTHORISATION NUMBER Vm 00879/4040 9. DATE OF FIRST AUTHORISATION 17 April 2003 Page 6 of 7
10. DATE OF REVISION OF THE TEXT September 2018 Approved: 27 September 2018 Page 7 of 7
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT MILBEMAX chewable tablets for small dogs and puppies SE: Milbemax vet. chewable tablets for small dogs and puppies 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One chewable tablet contains: Active substances: Milbemycin oxime Praziquantel 2.5 mg 25.0 mg Excipients: Propylene glycol (E 1520) 0.91 mg Iron oxide, brown (E 172) 0.66 mg Butylhydroxyanisole (E 320) 0.26 mg Propyl gallate (E 310) 0.09 mg For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Chewable tablet Oval shaped, dark brown. 4. CLINICAL PARTICULARS 4.1 Target species Dogs 4.2 Indications for use, specifying the target species In dogs: treatment of mixed infections by adult cestodes and nematodes of the following species susceptible to praziquantel and milbemycin oxime: - Cestodes: Dipylidium caninum Taenia spp. Echinococcus spp. Mesocestoides spp. - Nematodes: Ancylostoma caninum Toxocara canis Toxascaris leonina Trichuris vulpis Page 1 of 7
Crenosoma vulpis Angiostrongylus vasorum (Reduction of the level of infection by immature adult (L5) and adult parasite stages) (see specific treatment and prevention disease schedules under section 4.9 Amounts to be administered and administration route ) Thelazia callipaeda (see specific treatment schedule under section 4.9 Amounts to be administered and administration route ) The product can also be used in the prevention of heartworm disease (Dirofilaria immitis) if concomitant treatment against cestodes is indicated. 4.3 Contraindications Do not use in dogs weighing less than 1 kg. Do not use in cases of hypersensitivity to the active substances or to any of excipients. See also section 4.5 "Special precautions for use". 4.4 Special warnings for each target species It is recommended to treat all the animals living in the same household concomitantly. When infection with the cestode D. caninum has been confirmed, concomitant treatment against intermediate hosts, such as fleas and lice, should be discussed with a veterinarian to prevent re-infection. The use of the product should follow the implementation of appropriate diagnostic measures towards mixed infections by nematodes and cestodes with consideration of animal history and characteristics (e.g. age, health status), environment (e.g. kennelled dogs, hunting dogs), feeding (e.g. access to raw meat), geographical location and travel. Judgement of the administration of the product in dogs at risk from mixed re-infections or in specific at risk situations (such as zoonotic risks), should be made by the veterinarian responsible. 4.5 Special precautions for use Special precautions for use in animals Studies with milbemycin oxime indicate that the margin of safety in certain dogs of Collie or related breeds is less than in other breeds. In these dogs, the recommended dose should be strictly observed. The tolerance of the product in young puppies from these breeds has not been investigated. Clinical signs in Collies are similar to those seen in the general dog population when overdosed (see section 4.10 Overdose ). Treatment of dogs with a high number of circulating microfilariae can sometimes lead to the appearance of hypersensitivity reactions, such as pale mucous membranes, vomiting, trembling, laboured breathing or excessive salivation. These reactions are associated with the release of proteins from dead or dying microfilariae and are not a direct toxic effect of the product. The use in dogs suffering from microfilaremia is thus not recommended. In heartworm risk-areas, or in the case it is known that a dog has been travelling to and from heartworm risk regions, before using the product, a veterinary consultation is advised to exclude the presence of any concurrent infestation of Dirofilaria immitis. Page 2 of 7
In the case of a positive diagnosis, adulticidal therapy is indicated before administering the product. No studies have been performed with severely debilitated dogs or individuals with seriously compromised kidney or liver function. The product is not recommended for such animals or only according to a benefit/risk assessment by the responsible veterinarian. In dogs less than 4 weeks old, tape worm infection is unusual. Treatment of animals less than 4 weeks old with a combination product may therefore not be necessary. Parasite resistance to any particular class of anthelmintic may develop following frequent, repeated use of an anthelmintic of that class. Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use. People with known hypersensitivity to any of the ingredients should avoid contact with the veterinary medicinal product. In case of accidental ingestion of the tablets, particularly by a child, seek medical advice immediately and show the package leaflet or the label to the physician. Echinococcosis represents a hazard for humans. In case of Echinococcosis, specific guidelines on the treatment and follow up and on the safeguard of persons have to be followed. Experts or institutes of parasitology should be consulted. 4.6 Adverse reactions (frequency and seriousness) In very rare occasions, hypersensitivity reactions, systemic signs (such as lethargy), neurological signs (such as muscle tremors, ataxia and convulsions) and/or gastrointestinal signs (such as emesis, drooling, diarrhoea and anorexia) have been observed in dogs after administration of the veterinary medicinal product. The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals treated displaying adverse reaction(s)) - common (more than 1 but less than 10 animals in 100 animals treated) - uncommon (more than 1 but less than 10 animals in 1,000 animals treated) - rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports). 4.7 Use during pregnancy, lactation or lay The safety of the veterinary medicinal product has been established during pregnancy and lactation. Can be used in pregnant and lactating bitches. Can be used in breeding animals. 4.8 Interaction with other medicinal products and other forms of interaction No interactions were observed when the recommended dose of the macrocyclic lactone selamectin was administered during treatment with the product at the recommended dose. Although not recommended, the concomitant use of the product with a spot on containing moxidectin and imidacloprid at recommended dose rates following a single application was well tolerated in one experimental study by beagle dogs at the Page 3 of 7
age 11 months or older. Transient neurological adverse reactions (poor proprioception, flaccid frontal and hind legs, incoordination, slight tremors and high stepping gait of the hind limbs only) were observed after concurrent administration of both products in another study conducted in puppies aged 8-12 weeks. Such signs were however not observed in this study after giving MILBEMAX alone. The safety and efficacy of this combination have not been investigated in field studies. In the absence of further studies, caution should be taken in the case of concurrent use of MILBEMAX and any other macrocyclic lactone. Also, no such studies have been performed with reproducing animals, Collies, related breeds and their crosses. 4.9 Amounts to be administered and administration route Minimum recommended dose rate: 0.5 mg of milbemycin oxime and 5 mg of praziquantel per kg are given once orally. The product should be administered with or after some food. Depending on the bodyweight of the dog, the practical dosing is as follows: Weight Number of Tablet 1 5 kg 1 tablet To ensure a correct dosage, body weight should be determined as accurately as possible to avoid under dosing. In cases when heartworm disease prevention is used and at the same time treatment against tapeworm is required, the product can replace the monovalent product for the prevention of heartworm disease. For treatment of Angiostrongylus vasorum infections, milbemycin oxime should be given four times at weekly intervals. It is recommended, where concomitant treatment against cestodes is indicated, to treat once with the product and continue with the monovalent product containing milbemycin oxime alone, for the remaining three weekly treatments. In endemic areas administration of the product every four weeks will prevent angiostrongylosis by reducing immature adult (L5) and adult parasite burden, where concomitant treatment against cestodes is indicated. For the treatment of Thelazia callipaeda, milbemycin oxime should be given in 2 treatments, seven days apart. Where concomitant treatment against cestodes is indicated, the product can replace the monovalent product containing milbemycin oxime alone. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary The adverse reactions observed are the same as those observed at the recommended dose (see section 4.6 Adverse reactions (frequency and seriousness) ) but more pronounced. Page 4 of 7