ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1
1. NAME OF THE VETERINARY MEDICINAL PRODUCT Loxicom 0.5 mg/ml oral suspension for dogs 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains: Active Substance: Meloxicam Excipients: Sodium benzoate 0.5 mg 1.5 mg For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Pale yellow oral suspension. 4. CLINICAL PARTICULARS 4.1 Target species Dogs. 4.2 Indications for use, specifying the target species Alleviation of inflammation and pain in both acute and chronic musculo-skeletal disorders in dogs. 4.3 Contraindications Do not use in pregnant or lactating animals. Do not use in animals suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders. Do not use in case of hypersensitivity to the active substance or to any of the excipients Do not use in dogs less than 6 weeks of age. 4.4 Special warnings for each target species None. 4.5 Special precautions for use Special precautions for use in animals If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought. Avoid use in any dehydrated, hypovolaemic or hypotensive animal, as there is a potential risk of renal toxicity. Special precautions to be taken by the person administering the veterinary medicinal product to animals 2
People with known hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) should avoid contact with the veterinary medicinal product. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) Typical adverse reactions of NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, apathy and renal failure have occasionally been reported. In very rare cases, haemorrhagic diarrhoea, haematemesis, gastrointestinal ulceration and elevated liver enzymes have been reported. These adverse reactions occur generally within the first treatment week and are in most cases transient and disappear following termination of the treatment but in very rare cases may be serious or fatal. 4.7 Use during pregnancy, lactation or lay The safety of the veterinary medicinal product has not been established during pregnancy and lactation (see section 4.3). 4.8 Interaction with other medicinal products and other forms of interaction Other NSAIDs, diuretics, anticoagulants, aminoglycoside antibiotics and substances with high protein binding may compete for binding and thus lead to toxic effects. Loxicom must not be administered in conjunction with other NSAIDs or glucocorticosteroids. Pre-treatment with anti-inflammatory substances may result in additional or increased adverse effects and accordingly a treatment-free period with such veterinary medicinal products should be observed for at least 24 hours before commencement of treatment. The treatment-free period, however, should take into account the pharmacokinetic properties of the products used previously. 4.9 Amounts to be administered and administration route Oral use. To be administered with food or directly into the mouth. Shake well before use. Initial treatment is a single dose of 0.2 mg meloxicam/kg bodyweight (i.e. 4 ml/10 kg bodyweight) on the first day. Treatment is to be continued once daily by oral administration (at 24 hour intervals) at a maintenance dose of 0.1 mg meloxicam/kg bodyweight (i.e. 2 ml/10 kg bodyweight). For longer term treatment, once clinical response has been observed (after 4 days), the dose can be adjusted to the lowest effective individual dose reflecting that the degree of pain and inflammation associated with chronic musculo-skeletal disorders may vary over time. Particular care should be taken with regard to the accuracy of dosing. The suspension can be given using either of the two measuring syringes provided in the package. The syringes fit onto the bottle and have a kg-bodyweight scale which corresponds to the maintenance dose (i.e. 0.1 mg meloxicam/kg bodyweight). Thus for the first day, twice the maintenance volume will be required. Alternatively therapy may be initiated with Loxicom 5 mg/ml solution for injection. A clinical response is normally seen within 3-4 days. Treatment should be discontinued after 10 days at the latest if no clinical improvement is apparent. Avoid introduction of contamination during use. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary In the case of overdose, symptomatic treatment should be initiated. 3
4.11 Withdrawal period Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Anti-inflammatory and anti-rheumatic products, non-steroids (oxicams). ATCvet code: QM01AC06 5.1 Pharmacodynamic properties Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, anti-exudative and antipyretic effects. It reduces leukocyte infiltration into the inflamed tissue. To a minor extent it also inhibits collagen-induced thrombocyte aggregation. In vitro and in vivo studies demonstrated that meloxicam inhibits cyclooxygenase-2 (COX-2) to a greater extent than cyclooxygenase-1 (COX-1). 5.2 Pharmacokinetic particulars Absorption Meloxicam is completely absorbed following oral administration and maximal plasma concentrations are obtained after approximately 4.5 hours. When the product is used according to the recommended dosage regime, steady state concentrations of meloxicam in plasma are reached on the second day of treatment. Distribution There is a linear relationship between the dose administered and plasma concentration observed in the therapeutic dose range. Approximately 97 % of meloxicam is bound to plasma proteins. The volume of distribution is 0.3 l/kg. Metabolism Meloxicam is predominantly found in plasma and is also a major biliary excretion product whereas urine contains only traces of the parent compound. Meloxicam is metabolised to an alcohol, an acid derivative and to several polar metabolites. All major metabolites have been shown to be pharmacologically inactive. Elimination Meloxicam is eliminated with a half-life of 24 hours. Approximately 75 % of the administered dose is eliminated via faeces and the remainder via urine. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Sodium Benzoate Glycerol Povidone K30 Xanthan Gum Disodium Phosphate Dihydrate Sodium Dihydrogen Phosphate Dihydrate Citric Acid Anhydrous Simethicone Emulsion Purified water 4
6.2 Incompatibilities In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products. 6.3 Shelf-life Shelf-life of the veterinary medicinal product as packaged for sale: 18 months Shelf-life after first opening the immediate packaging: 6 months 6.4 Special precautions for storage This veterinary medicinal product does not require any special storage conditions. 6.5 Nature and composition of immediate packaging The veterinary medicinal product is presented in 15 ml and 30 ml polyethylene terephthalate screw bottles with HDPE/LDPE child resistant caps. Two polyethylene/polypropylene measuring syringes, a 1 ml and a 5 ml syringe, are supplied with each bottle to ensure accurate dosing of small and large dogs. Each syringe is graduated in bodyweight, the 1 ml syringe is graduated from 0.25 kg to 5.0 kg and the 5 ml syringe for 1 kg to 25 kg. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste material 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. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Newry Co. Down, BT35 6JP United Kingdom 8. MARKETING AUTHORISATION NUMBER EU/2/08/090/001 EU/2/08/090/002 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 10/02/2009 Date of last renewal: 12/03/2014 10. DATE OF REVISION OF THE TEXT Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/. 5
PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. 6
1. NAME OF THE VETERINARY MEDICINAL PRODUCT Loxicom 1.5 mg/ml oral suspension for dogs. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains: Active Substance: Meloxicam Excipients: Sodium Benzoate 1.5 mg 1.5 mg For a full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Pale yellow oral suspension. 4. CLINICAL PARTICULARS 4.1 Target species Dogs. 4.2 Indications for use, specifying the target species Alleviation of inflammation and pain in both acute and chronic musculo-skeletal disorders in dogs. 4.3 Contraindications Do not use in pregnant or lactating animals. Do not use in animals suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders. Do not use in case of hypersensitivity to the active substance or to any of the excipients. Do no use in dogs less than 6 weeks of age. 4.4 Special warnings for each target species None. 4.5 Special precautions for use Special precautions for use in animals If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought. Avoid use in any dehydrated, hypovolaemic or hypotensive animal, as there is a potential risk of renal toxicity. Special precautions to be taken by the person administering the veterinary medicinal product to animals 7
People with known hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) should avoid contact with the veterinary medicinal product. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) Typical adverse reactions of NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, apathy and renal failure have occasionally been reported. In very rare cases haemorrhagic diarrhoea, haematemesis, gastrointestinal ulceration and elevated liver enzymes have been reported. These adverse reactions occur generally within the first treatment week and are in most cases transient and disappear following termination of the treatment but in very rare cases may be serious or fatal. 4.7 Use during pregnancy, lactation or lay The safety of the veterinary medicinal product has not been established during pregnancy and lactation (see section 4.3). 4.8 Interaction with other medicinal products and other forms of interaction Other NSAIDs, diuretics, anticoagulants, aminoglycoside antibiotics and substances with high protein binding may compete for binding and thus lead to toxic effects. Loxicom must not be administered in conjunction with other NSAIDs or glucocorticosteroids. Pre-treatment with anti-inflammatory substances may result in additional or increased adverse effects and accordingly a treatment-free period with such veterinary medicinal products should be observed for at least 24 hours before commencement of treatment. The treatment-free period, however, should take into account the pharmacokinetic properties of the products used previously. 4.9 Amounts to be administered and administration route Oral use. To be administered with food or directly into the mouth. Shake well before use. Initial treatment is a single dose of 0.2 mg meloxicam/kg bodyweight (i.e. 1.33 ml/10 kg bodyweight) on the first day. Treatment is to be continued once daily by oral administration (at 24 hour intervals) at a maintenance dose of 0.1 mg meloxicam/kg bodyweight (i.e. 0.667 ml/10 kg bodyweight). For longer term treatment, once clinical response has been observed (after 4 days), the dose can be adjusted to the lowest effective individual dose reflecting that the degree of pain and inflammation associated with chronic musculo-skeletal disorders may vary over time. Particular care should be taken with regard to the accuracy of dosing. The suspension can be given using either of the two measuring syringes provided in the package (depending on weight of dog). The syringes fit onto the bottle and have a kg-bodyweight scale which corresponds to the maintenance dose (i.e. 0.1 mg meloxicam/kg bodyweight). Thus for the first day, twice the maintenance volume will be required. Alternatively therapy may be initiated with Loxicom 5 mg/ml solution for injection. A clinical response is normally seen within 3-4 days. Treatment should be discontinued after 10 days at the latest if no clinical improvement is apparent. Avoid introduction of contamination during use. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary 8
In the case of overdose, symptomatic treatment should be initiated. 4.11 Withdrawal period(s) Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Anti-inflammatory and anti-rheumatic products, non-steroids (oxicams). ATCvet code: QM01AC06 5.1 Pharmacodynamic properties Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, anti-exudative and antipyretic effects. It reduces leukocyte infiltration into the inflamed tissue. To a minor extent it also inhibits collagen-induced thrombocyte aggregation. In vitro and in vivo studies demonstrated that meloxicam inhibits cyclooxygenase-2 (COX-2) to a greater extent than cyclooxygenase-1 (COX-1). 5.2 Pharmacokinetic particulars Absorption Meloxicam is completely absorbed following oral administration and maximal plasma concentrations are obtained after approximately 4.5 hours. When the product is used according to the recommended dosage regime, steady state concentrations of meloxicam in plasma are reached on the second day of treatment. Distribution There is a linear relationship between the dose administered and plasma concentration observed in the therapeutic dose range in dogs. Approximately 97 % of meloxicam is bound to plasma proteins. The volume of distribution is 0.3 l/kg. Metabolism Meloxicam is predominantly found in plasma and is also a major biliary excretion product whereas urine contains only traces of the parent compound. Meloxicam is metabolised to an alcohol, an acid derivative and to several polar metabolites. All major metabolites have been shown to be pharmacologically inactive. Elimination Meloxicam is eliminated with a half-life of 24 hours. Approximately 75 % of the administered dose is eliminated via faeces and the remainder via urine. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Sodium Benzoate Glycerol Povidone K30 Xanthan Gum Disodium Phosphate Dihydrate Sodium Dihydrogen Phosphate Dihydrate Citric Acid Anhydrous Simethicone Emulsion 9
Purified water 6.2 Incompatibilities None known. 6.3 Shelf-life Shelf-life of the veterinary medicinal product as packaged for sale: 18 months Shelf-life after first opening the immediate packaging: 6 months 6.4 Special precautions for storage This veterinary medicinal product does not require any special storage conditions. 6.5 Nature and composition of immediate packaging The veterinary medicinal product is presented in 10 ml, 32 ml, 100 ml, 2 x 100 ml and 200 ml polyethylene terephthalate screw bottles with HDPE/LDPE child resistant caps. Two polyethylene/polypropylene measuring syringes, a 1 ml and 5 ml syringe, are supplied with each bottle to ensure accurate dosing of small and large dogs. Each syringe is graduated in bodyweight, the 1 ml syringe is graduated from 0.5 kg to 15 kg and the 5 ml syringe for 2.5 kg to 75 kg. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste material 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. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Newry Co Down, BT35 6JP United Kingdom 8. MARKETING AUTHORISATION NUMBER(S) EU/2/08/090/003 EU/2/08/090/004 EU/2/08/090/005 EU/2/08/090/032 EU/2/08/090/033 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 10/02/2009 Date of last renewal: 12/03/2014 10. DATE OF REVISION OF THE TEXT 10
Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/. PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. 11
1. NAME OF THE VETERINARY MEDICINAL PRODUCT Loxicom 5 mg/ml solution for injection for dogs and cats. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains: Active Substance: Meloxicam Excipients: Ethanol, anhydrous 5 mg 150 mg For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Pale yellow solution for injection. 4. CLINICAL PARTICULARS 4.1 Target species Dogs and cats. 4.2 Indications for use, specifying the target species Dogs: Alleviation of inflammation and pain in both acute and chronic musculo-skeletal disorders. Reduction of post-operative pain and inflammation following orthopaedic and soft tissue surgery. Cats: Reduction of post-operative pain after ovariohysterectomy and minor soft tissue surgery. 4.3 Contraindications Do not use in pregnant or lactating animals. Do not use in animals suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders. Do not use in case of hypersensitivity to the active substance or to any of the excipients. Do not use in animals less than 6 weeks of age nor in cats of less than 2 kg. 4.4 Special warnings for each target species For post-operative pain relief in cats, safety has only been documented after thiopental/halothane anaesthesia. 4.5 Special precautions for use Special precautions for use in animals If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought. 12
Avoid use in any dehydrated, hypovolaemic or hypotensive animal, as there is a potential risk of renal toxicity. During anaesthesia, monitoring and fluid therapy should be considered as standard practice. Special precautions to be taken by the person administering the veterinary medicinal product to animals Accidental self-injection may give rise to pain. People with known hypersensitivity to NSAIDs should avoid contact with the veterinary medicinal product. In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) Typical adverse reactions of NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, apathy and renal failure have occasionally been reported. In very rare cases elevated liver enzymes have been reported. In dogs, in very rare cases, haemorrhagic diarrhoea, haematemesis and gastrointestinal ulceration have been reported. In dogs, these adverse reactions occur generally within the first treatment week and are in most cases transient and disappear following termination of the treatment but in very rare cases may be serious or fatal. In very rare cases anaphylactoid reactions may occur and should be treated symptomatically. 4.7 Use during pregnancy, lactation or lay The safety of the veterinary medicinal product has not been established during pregnancy and lactation (see section 4.3). 4.8 Interaction with other medicinal products and other forms of interaction Other NSAIDs, diuretics, anticoagulants, aminoglycoside antibiotics and substances with high protein binding may compete for binding and thus lead to toxic effects. Loxicom must not be administered in conjunction with other NSAIDs or glucocorticosteroids. Concurrent administration of potential nephrotoxic drugs should be avoided. In animals at anaesthetic risk (e.g. aged animals) intravenous or subcutaneous fluid therapy during anaesthesia should be taken into consideration. When anaesthesia and NSAID are concomitantly administered, a risk for renal function cannot be excluded. Pre-treatment with anti-inflammatory substances may result in additional or increased adverse effects and accordingly a treatment-free period with such drugs should be observed for at least 24 hours before commencement of treatment. The treatment-free period, however, should take into account the pharmacokinetic properties of the products used previously. 4.9 Amounts to be administered and administration route Dogs: Musculo-skeletal disorders: Single subcutaneous injection at a dosage of 0.2 mg meloxicam/kg bodyweight (i.e. 0.4 ml/10 kg bodyweight). Loxicom 1.5 mg/ml oral suspension and Loxicom 0.5 mg/ml oral suspension may be used for continuation of treatment at a dosage of 0.1 mg meloxicam/kg bodyweight, 24 hours after administration of the injection. Reduction of post-operative pain (over a period of 24 hours): Single intravenous or subcutaneous injection at a dosage of 0.2 mg meloxicam/kg bodyweight (i.e. 0.4 ml/10 kg bodyweight) before surgery, for example at the time of induction of anaesthesia. Cats: 13
Reduction of post-operative pain in cats where no oral follow-up treatment is possible e.g. feral cats: Single subcutaneous injection at a dosage of 0.3 mg meloxicam/kg bodyweight (i.e. 0.06 ml/kg bodyweight) before surgery, for example at the time of induction of anaesthesia. In this case do not use oral follow up treatment. Reduction of post-operative pain in cats when administration of meloxicam is to be continued as an oral follow-up therapy: Single subcutaneous injection at a dosage of 0.2 mg meloxicam/kg body weight (i.e. 0.04 ml/kg body weight) before surgery, for example at the time of induction of anaesthesia. To continue treatment for up to five days, this initial dose may be followed 24 hours later by administration of Loxicom 0.5 mg/ml oral suspension for cats at a dosage of 0.05 mg meloxicam/kg body weight. The oral follow-up dose may be administered for up to a total of four doses at 24 hour intervals.. Particular care should be taken with regard to the accuracy of dosing. A suitably graduated 1 ml syringe should be used for administration of the product to cats. Avoid introduction of contamination during use. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary In the case of overdose, symptomatic treatment should be initiated. 4.11 Withdrawal period(s) Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Anti-inflammatory and anti-rheumatic products, non-steroids (oxicams). ATCvet code: QM01AC06 5.1 Pharmacodynamic properties Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, anti-exudative and antipyretic effects. It reduces leukocyte infiltration into the inflamed tissue. To a minor extent it also inhibits collagen-induced thrombocyte aggregation. In vitro and in vivo studies demonstrated that meloxicam inhibits cyclooxygenase-2 (COX-2) to a greater extent than cyclooxygenase-1 (COX-1). 5.2 Pharmacokinetic particulars Absorption Following subcutaneous administration, meloxicam is completely bioavailable and maximal mean plasma concentrations of 0.73 µg/ml in dogs and 1.1 µg/ml in cats were reached approximately 2.5 hours and 1.5 hours post-administration, respectively. Distribution There is a linear relationship between the dose administered and plasma concentration observed in the therapeutic dose range in dogs. More than 97 % of meloxicam is bound to plasma proteins. The volume of distribution is 0.3 l/kg in dogs and 0.09 l/kg in cats. Metabolism In dogs, meloxicam is predominantly found in plasma and is also a major biliary excretion product whereas urine contains only traces of the parent compound. Meloxicam is metabolised to an alcohol, 14
an acid derivative and to several polar metabolites. All major metabolites have been shown to be pharmacologically inactive. Elimination Meloxicam is eliminated with a half-life of 24 hours in dogs and 15 hours in cats. Approximately 75 % of the administered dose is eliminated via faeces and the remainder via urine. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Meglumine Glycine Ethanol (anhydrous) Poloxamer 188 Sodium Chloride Glycofurol Sodium Hydroxide (for ph adjustment) Hydrochloric Acid (for ph adjustment) Water for Injection 6.2 Incompatibilities In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products. 6.3 Shelf-life Shelf-life of the veterinary medicinal product as packaged for sale: 18 months. Shelf-life after first opening the immediate packaging: 28 days 6.4 Special precautions for storage This veterinary medicinal product does not require any special storage conditions. 6.5 Nature and composition of immediate packaging Colourless glass injection vial of 10, 20 or 100 ml, closed with a bromobutyl stopper and sealed with an aluminium cap. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste material 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. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Newry Co Down, BT35 6JP United Kingdom 15
8. MARKETING AUTHORISATION NUMBER(S) EU/2/08/090/006 EU/2/08/090/007 EU/2/08/090/008 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 10/02/2009 Date of last renewal: 12/03/2014 10. DATE OF REVISION OF THE TEXT Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/. PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. 16
1. NAME OF THE VETERINARY MEDICINAL PRODUCT Loxicom 0.5 mg/ml oral suspension for cats. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains: Active Substance: Meloxicam Excipient: Sodium benzoate 0.5 mg 1.5 mg For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Pale yellow oral suspension. 4. CLINICAL PARTICULARS 4.1 Target species Cats. 4.2 Indications for use, specifying the target species Alleviation of mild to moderate post-operative pain and inflammation following surgical procedures in cats, e.g. orthopaedic and soft tissue surgery. Alleviation of inflammation and pain in acute and chronic musculo-skeletal disorders in cats. 4.3 Contraindications Do not use in pregnant or lactating cats. Do not use in cats suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders. Do not use in case of hypersensitivity to the active substance or to any of the excipients Do not use in cats less than 6 weeks of age. 4.4 Special warnings for each target species None. 4.5 Special precautions for use Special precautions for use in animals If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought. Avoid use in any dehydrated, hypovolaemic or hypotensive animal, as there is a potential risk of renal toxicity. Post-operative pain and inflammation following surgical procedures: 17
In case additional pain relief is required, multimodal pain therapy should be considered. Chronic musculoskeletal disorders: Response to long-term therapy should be monitored at regular intervals by a veterinary surgeon. Special precautions to be taken by the person administering the veterinary medicinal product to animals People with known hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) should avoid contact with the veterinary medicinal product. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) Typical adverse reactions of NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, apathy and renal failure have occasionally been reported. In very rare cases elevated liver enzymes have been reported. These adverse reactions occur generally within the first treatment week and are in most cases transient and disappear following termination of the treatment but in very rare cases may be serious or fatal. 4.7 Use during pregnancy, lactation or lay The safety of the veterinary medicinal product has not been established during pregnancy and lactation (see section 4.3). 4.8 Interaction with other medicinal products and other forms of interaction Other NSAIDs, diuretics, anticoagulants, aminoglycoside antibiotics and substances with high protein binding may compete for binding and thus lead to toxic effects. Loxicom must not be administered in conjunction with other NSAIDs or glucocorticosteroids. Concurrent administration of potential nephrotoxic drugs should be avoided. Pre-treatment with anti-inflammatory substances may result in additional or increased adverse effects and accordingly a treatment-free period with such veterinary medicinal products should be observed for at least 24 hours before commencement of treatment. The treatment-free period, however, should take into account the pharmacological properties of the products used previously. 4.9 Amounts to be administered and administration route Oral use. To be administered with food or directly into the mouth. Shake well before use. Dosage Post-operative pain and inflammation following surgical procedures: After initial treatment with Loxicom 5 mg/ml Solution for Injection for Dogs and Cats continue treatment 24 hours later with Loxicom 0.5 mg/ml oral suspension for cats at a dosage of 0.05 mg meloxicam/kg body weight. The oral follow-up dose may be administered once daily (at 24-hour intervals) for up to four days. Acute musculo-skeletal disorders: Initial treatment is a single oral dose of 0.2 mg meloxicam/kg body weight on the first day. Treatment is to be continued once daily by oral administration (at 24-hour intervals) at a dose of 0.05 mg meloxicam/kg body weight for as long as acute pain and inflammation persist. Chronic musculo-skeletal disorders: 18
Initial treatment is a single dose of 0.1 mg meloxicam/kg bodyweight on the first day. Treatment is to be continued once daily by oral administration (at 24 hour intervals) at a maintenance dose of 0.05 mg meloxicam/kg bodyweight. A clinical response is normally seen within 7 days. Treatment should be discontinued after 14 days at the latest if no clinical improvement is apparent. Dosing Procedure: The syringe fits onto the bottle and has a kg-body weight scale which corresponds to the maintenance dose. Thus for initiation of the treatment of chronic musculo-skeletal disorders on the first day, twice the maintenance volume will be required. For initiation of the treatment of acute musculo-skeletal disorders on the first day, 4 times the maintenance volume will be required. Particular care should be taken with regard to the accuracy of dosing. The recommended dose should not be exceeded. The suspension should be given using the Loxicom measuring syringe provided in the package. Avoid introduction of contamination during use. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary Meloxicam has a narrow therapeutic safety margin in cats and clinical signs of overdose may be seen at relatively small overdose levels. In the case of overdose, adverse reactions (as listed in Section 4.6) are expected to be more severe and more frequent. In the case of overdose symptomatic treatment should be initiated. 4.11 Withdrawal period Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic Group: Anti-inflammatory and antirheumatic products, non-steroids (oxicams). ATCvet code: QM01AC06 5.1 Pharmacodynamic properties Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, anti-exudative and antipyretic effects. It reduces leukocyte infiltration into the inflamed tissue. To a minor extent it also inhibits collagen-induced thrombocyte aggregation. In vitro and in vivo studies demonstrated that meloxicam inhibits cyclooxygenase-2 (COX-2) to a greater extent than cyclooxygenase-1 (COX-1). 5.2 Pharmacokinetic particulars Absorption If the animal is fasted when dosed, the maximal plasma concentrations are obtained after approximately 3 hours. If the animal is fed at the time of dosing, the absorption may be slightly delayed. Due to the loading dose, steady is reached after 2 days (48h). Distribution There is a linear relationship between the dose administered and plasma concentration observed in the therapeutic dose range. Approximately 97 % of meloxicam is bound to plasma proteins. Metabolism 19
Meloxicam is predominantly found in plasma and is also a major biliary excretion product whereas urine contains only traces of the parent compound. Meloxicam is metabolised to an alcohol, an acid derivative and to several polar metabolites. All major metabolites have been shown to be pharmacologically inactive. Elimination Meloxicam is eliminated with a half-life of 24 hours. Approximately 75 % of the administered dose is eliminated via faeces and the remainder via urine. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Sodium Benzoate Glycerol Povidone K30 Xanthan Gum Disodium Phosphate Dihydrate Sodium Dihydrogen Phosphate Dihydrate Citric Acid Anhydrous Simethicone Emulsion Purified water 6.2 Incompatibilities In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products. 6.3 Shelf-life Shelf-life of the veterinary medicinal product as packaged for sale: 18 months Shelf-life after first opening the immediate packaging: 6 months 6.4 Special precautions for storage This veterinary medicinal product does not require any special storage conditions. 6.5 Nature and composition of immediate packaging The veterinary medicinal product is presented in 5 ml, 15 ml and 30 ml polyethylene terephthalate screw bottles with HDPE/LDPE child resistant caps. The 1 ml measuring syringe has a kg-body weight scale for cats (0.5 to 10 kg). Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste material 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. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works 20
Newry Co. Down, BT35 6JP United Kingdom 8. MARKETING AUTHORISATION NUMBER EU/2/08/090/009 EU/2/08/090/027 EU/2/08/090/028 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 10/02/2009 Date of last renewal: 12/03/2014 10. DATE OF REVISION OF THE TEXT Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/. PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. 21
1. NAME OF THE VETERINARY MEDICINAL PRODUCT Loxicom 20 mg/ml solution for injection for cattle, pigs and horses. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One ml contains: Active substance: Meloxicam 20 mg Excipient: Ethanol 150 mg For a full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Solution for injection. A yellow solution. 4. CLINICAL PARTICULARS 4.1 Target species Cattle, pigs and horses. 4.2 Indications for use, specifying the target species Cattle: For use in acute respiratory infection with appropriate antibiotic therapy to reduce clinical signs in cattle. For use in diarrhoea in combination with oral re-hydration therapy to reduce clinical signs in calves of over one week of age and young, non-lactating cattle. For adjunctive therapy in the treatment of acute mastitis, in combination with antibiotic therapy. For the relief of post-operative pain following dehorning in calves. Pigs: For use in non-infectious locomotor disorders to reduce the symptoms of lameness and inflammation. For adjunctive therapy in the treatment of puerperal septicaemia and toxaemia (mastitis-metritisagalactia syndrome) with appropriate antibiotic therapy. Horses: For use in the alleviation of inflammation and relief of pain in both acute and chronic musculo-skeletal disorders. For the relief of pain associated with equine colic. 4.3 Contraindications See also section 4.7. Do not use in horses less than 6 weeks of age. Do not use in animals suffering from impaired hepatic, cardiac or renal function and haemorrhagic disorders, or where there is evidence of ulcerogenic gastrointestinal lesions. Do not use in case of hypersensitivity to the active substance or to any of the excipients. 22
For the treatment of diarrhoea in cattle, do not use in animals of less than one week of age. 4.4 Special warnings for each target species Treatment of calves with Loxicom 20 minutes before dehorning reduces post-operative pain. Loxicom alone will not provide adequate pain relief during the dehorning procedure. To obtain adequate pain relief during surgery co-medication with an appropriate analgesic is needed. 4.5 Special precautions for use Special precautions for use in animals If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought. Avoid use in very severely dehydrated, hypovolaemic or hypotensive animals which require parenteral rehydration, as there may be a potential risk of renal toxicity. In cases of inadequate relief of pain when used in the treatment of equine colic, careful re-evaluation of the diagnosis should be made as this could indicate the need for surgical intervention. Special precautions to be taken by the person administering the veterinary medicinal product to animals Accidental self injection may cause pain. People with known hypersensitivity to Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) should avoid contact with the veterinary medicinal product. In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) Administration of the veterinary medicinal product by the subcutaneous route in cattle and the intramuscular route in pigs is well tolerated; only a slight transient swelling at the injection site following subcutaneous administration was observed in cattle treated in clinical studies In horses, a transient swelling at the injection site can occur but resolved without intervention. In very rare cases anaphylactoid reactions may occur and should be treated symptomatically. 4.7 Use during pregnancy, lactation or lay Cattle and Pigs: Can be used during pregnancy and lactation. Horses: Do not use in pregnant or lactating mares. See also section 4.3. 4.8 Interaction with other medicinal products and other forms of interaction Do not administer concurrently with glucocorticosteroids, other non-steroidal anti-inflammatory drugs or with anti-coagulant agents. 4.9 Amounts to be administered and administration route Cattle: Single subcutaneous or intravenous injection at a dosage of 0.5 mg meloxicam/kg body weight (i.e., 2.5 ml/100 kg body weight) in combination with antibiotic therapy or with oral re-hydration therapy, as appropriate. The recommended maximum volume to be administered at a single injection site is 10 ml. 23
Pigs: Single intramuscular injection at a dosage of 0.4 mg meloxicam/kg body weight (i.e., 2.0 ml/100 kg body weight) in combination with antibiotic therapy, as appropriate. If required, a second administration of meloxicam can be given after 24 hours. The recommended maximum volume to be administered at a single injection site is 2 ml. Horses: Single intravenous injection as a dosage of 0.6 mg meloxicam/kg body weight (i.e., 3.0 ml/100 kg body weight). For use in the alleviation of inflammation and the relief of pain in both acute and chronic musculoskeletal disorders, a suitable oral therapy containing meloxicam, administered in accordance with label recommendations, may be used for continuation of treatment. Avoid introduction of contamination during use. Do not exceed 50 broachings per vial. If more than 50 broachings are required, the use of a draw-off needle is recommended. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary In the case of overdose, symptomatic treatment should be initiated. 4.11 Withdrawal period Cattle: Meat and offal: 15 days Milk: 5 days Pigs: Meat and offal: 5 days Horses: Meat and offal: 5 days. Not authorised for use in horses producing milk for human consumption. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids (oxicams) ATC vet code: QM01AC06 5.1 Pharmacodynamic properties Meloxicam is a Non-Steroidal Anti-Inflammatory Drug (NSAID) of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, anti-exudative, analgesic and antipyretic effects. It reduces leukocyte infiltration into the inflamed tissue. To a minor extent it also inhibits collagen-induced thrombocyte aggregation. Meloxicam also has anti-endotoxic properties because it has been shown to inhibit production of thromboxane B 2 induced by E. coli endotoxin administration in calves, lactating cows and pigs. 5.2 Pharmacokinetic particulars Absorption After a single subcutaneous dose of 0.5 mg meloxicam/kg, C max values of 2.1 μg/ml and 2.7 μg/ml were reached after 7.7 hours and 4 hours in young cattle and lactating cows, respectively. After two intramuscular doses of 0.4 mg meloxicam/kg, a C max value of 1.9 μg/ml was reached after 1 hour in pigs. Distribution More than 98% of meloxicam is bound to plasma proteins. The highest meloxicam concentrations are to be found in liver and kidney. Comparatively low concentrations are detectable in skeletal muscle and fat. Metabolism 24
Meloxicam is predominantly found in plasma. In cattle, meloxicam is also a major excretion product in milk and bile whereas urine contains only traces of the parent compound. In pigs, bile and urine contain only traces of the parent compound. Meloxicam is metabolised to an alcohol, an acid derivative and to several polar metabolites. All major metabolites have been shown to be pharmacologically inactive. The metabolism in horses has not been investigated. Elimination Meloxicam is eliminated with a half-life of 26 hours and 17.5 hours after subcutaneous injection in young cattle and lactating cows, respectively. In pigs, after intramuscular administration the mean plasma elimination half-life is approximately 2.5 hours. In horses, after intravenous injection meloxicam is eliminated with a terminal half-life of 8.5 hours. Approximately 50% of the administered dose is eliminated via urine and the remainder via faeces. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients - Ethanol - Meglumine - Glycine - Poloxamer 188 - Sodium chloride - Macrogol 300 - Hydrochloric acid - Sodium hydroxide - Water for injections 6.2 Incompatibilities In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products. 6.3 Shelf life Shelf life of the veterinary medicinal product as packaged for sale: 3 years. Shelf life after first opening the immediate packaging: 28 days. 6.4 Special precautions for storage This veterinary medicinal product does not require any special storage conditions. 6.5 Nature and composition of immediate packaging Cardboard box with either 1 or 12 colourless glass injection vial(s) each containing 30 ml, 50 ml or 100 ml. Cardboard box with 1, 6 or 12 colourless glass injection vial(s) each containing 250 ml. Each vial is closed with a bromobutyl bung and sealed with an aluminium cap. Not all pack sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products 25
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. 7. MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Newry Co Down, BT35 6JP United Kingdom 8. MARKETING AUTHORISATION NUMBERS: EU/2/08/090/010 30 ml EU/2/08/090/011 50 ml EU/2/08/090/012 100 ml EU/2/08/090/013 250 ml EU/2/08/090/014 6 x 250 ml EU/2/08/090/015 12 x 30 ml EU/2/08/090/016 12 x 50 ml EU/2/08/090/017 12 x 100 ml EU/2/08/090/018 12 x 250 ml 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 10/02/2009 Date of last renewal: 12/03/2014 10. DATE OF REVISION OF THE TEXT Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/. PROHIBITION OF SALE, SUPPLY AND/OR USE Not applicable. 26
1. NAME OF THE VETERINARY MEDICINAL PRODUCT Loxicom 1 mg chewable tablets for dogs Loxicom 2.5 mg chewable tablets for dogs 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each chewable tablet contains: Active substance: Meloxicam 1 mg Meloxicam 2.5 mg For a full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Chewable tablet. Light brown oval biconvex tablet with a score line on one face and plain on the other. The tablets can be broken into equal halves. 4. CLINICAL PARTICULARS 4.1 Target species Dogs 4.2 Indications for use, specifying the target species Alleviation of inflammation and pain in both acute and chronic musculo-skeletal disorders in dogs. 4.3 Contraindications Do not use in pregnant or lactating animals. Do not use in animals suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders Do not use in dogs less than 6 weeks of age or less than 4 kg body weight. Do not use in case of hypersensitivity to the active substance or to any of the excipients. 4.4 Special warnings for each target species None 4.5 Special precautions for use Special precautions for use in animals If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought. Avoid use in any dehydrated, hypovolaemic or hypotensive animal, as there is a potential risk of renal toxicity. This veterinary medicinal product for dogs should not be used in cats as it is not suitable for use in this species. In cats, a meloxicam containing oral suspension authorised for that species should be used. 27
Special precautions to be taken by the person administering the veterinary medicinal product to animals People with known hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) should avoid contact with the veterinary medicinal product. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. 4.6 Adverse reactions (frequency and seriousness) Typical adverse drug reactions of NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, apathy and renal failure have occasionally been reported. In very rare cases, haemorrhagic diarrhoea, haematemesis, gastrointestinal ulceration and elevated liver enzymes have been reported. These side effects occur generally within the first treatment week and are in most cases transient and disappear following termination of the treatment but in very rare cases may be serious or fatal. 4.7 Use during pregnancy, lactation or lay The safety of the veterinary medicinal product has not been established during pregnancy and lactation (see section 4.3). 4.8 Interaction with other medicinal products and other forms of interaction Other NSAIDs, diuretics, anticoagulants, aminoglycoside antibiotics and substances with high protein binding may compete for binding and thus lead to toxic effects. This veterinary medicinal product must not be administered in conjunction with other NSAIDs or glucocorticosteroids. Pre-treatment with anti-inflammatory substances may result in additional or increased adverse effects and accordingly a treatment-free period with such drugs should be observed for at least 24 hours before commencement of treatment. The treatment-free period, however, should take into account the pharmacological properties of the veterinary medicinal products used previously. 4.9 Amounts to be administered and administration route Oral use. Initial treatment is a single dose of 0.2 mg meloxicam/kg body weight on the first day. Treatment is to be continued once daily by oral administration (at 24-hour intervals) at a maintenance dose of 0.1 mg meloxicam/kg body weight. Alternatively, therapy may be initiated with a solution for injection containing 5 mg meloxicam/ml. Each chewable tablet contains 1 mg or 2.5 mg meloxicam, which corresponds to the daily maintenance dose for a 10 kg body weight dog, or a 25 kg body weight dog, respectively. Each chewable tablet can be halved for accurate dosing according to the individual body weight of the animal. The tablets can be administered with or without food, are flavoured and are taken by most dogs voluntarily. Dose scheme for the maintenance dose: 28
Body weight (kg) Number of chewable tablets 1 mg Number of chewable tablets 2.5 mg mg/kg 4.0-7.0 ½ 0.13-0.1 7.1-10.0 1 0.14-0.1 10.1-15.0 1½ 0.15-0.1 15.1-20.0 2 0.13-0.1 20.1-25.0 1 0.12-0.1 25.1-35.0 1½ 0.15-0.1 35.1-50.0 2 0.14-0.1 The use of a meloxicam containing oral suspension for dogs may be considered for an even more precise dosing. For dogs weighing less than 4 kg the use of meloxicam containing oral suspension for dogs is recommended. A clinical response is normally seen within 3-4 days. Treatment should be discontinued after 10 days if no clinical improvement is apparent. To ensure correct dosage, bodyweight should be determined as accurately as possible to avoid underdosing or overdosing. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary In case of overdose, symptomatic treatment should be initiated. 4.11 Withdrawal period Not applicable. 5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products, non-steroids (oxicams), ATC vet code: QM01AC06 5.1 Pharmacodynamic properties Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, anti-exudative and antipyretic effects. It reduces leukocyte infiltration into the inflamed tissue. To a minor extent it also inhibits collagen-induced thrombocyte aggregation. In vitro and in vivo studies demonstrated that meloxicam inhibits cyclooxygenase-2 (COX-2) to a greater extent than cyclooxygenase-1 (COX-1). 5.2 Pharmacokinetic properties Absorption Meloxicam is completely absorbed following oral administration and maximal plasma concentrations are obtained after approximately 7.5 hours. When the veterinary medicinal product is used according to the recommended dosage regime, steady state concentrations of meloxicam in plasma are reached on the second day of treatment. Distribution 29