Meloxidolor - summary of medicine characteristics

SUMMARY OF PRODUCT CHARACTERISTICS

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml contains:

Active substance:

Meloxicam 5 mg

Excipient:

Ethanol 150 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear yellow solution.

4. CLINICAL PARTICULARS4.1 Target species

Dogs, cats, cattle (calves) and pigs

• 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.

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.

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 the relief of post-operative pain associated with minor soft tissue surgery such as castration.

4.3 Contraindications

Do not use in cases of hypersensitivity to the active substance or to any of the excipients.

Do not use in dogs and cats suffering from gastrointestinal disorders such as irritation and haemorrhage, impaired hepatic, cardiac or renal function and haemorrhagic disorders.

Do not use in dogs and cats less than 6 weeks of age nor in cats of less than 2 kg.

Do not use in cattle and pigs suffering from impaired hepatic, cardiac or renal function and haemorrhagic disorders, or where there is evidence of ulcerogenic gastrointestinal lesions. For the treatment of diarrhoea in cattle, do not use in animals of less than one week of age. Do not use in pigs less than 2 days old.

See also section 4.7.

• 4.4 Special warnings for each target species

Treatment of piglets with Meloxidolor before castration reduces post-operative pain.

To obtain pain relief for cattle and pigs during surgery co-medication with an appropriate anaesthetic/se­dative/analge­sic is needed.

To obtain the best possible pain relieving effect for pigs post-surgery Meloxidolor should be administered 30 minutes before surgical intervention.

Treatment of calves with Meloxidolor 20 minutes before dehorning reduces post-operative pain. Meloxidolor alone will not provide adequate pain relief during the dehorning procedure.

• 4.5 Special precautions for use

Special precautions for use in animals

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. Any oral follow-up therapy using meloxicam or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) should not be administered in cats, as appropriate dosage regimens for such follow-up treatments have not been established.

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.

The veterinary medicinal product should not be administered by pregnant women or women of childbearing potential as Meloxicam may be harmful to the foetus and unborn child.

• 4.6 Adverse reactions (frequency and seriousness)

For dogs and cats:

Typical adverse reactions of NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, lethargy and renal failure have rarely been reported. In very rare cases elevated liver enzymes have been reported.

In very rare cases, haemorrhagic diarrhoea, haematemesis and gastrointestinal ulceration 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.

In very rare cases anaphylactoid reactions may occur and should be treated symptomatically.

If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought.

For cattle and pigs:

Only a slight transient swelling at the injection site following subcutaneous administration was observed in less than 10 % of the cattle treated in clinical studies.

In very rare cases anaphylactic reactions, which may be serious (including fatal), may occur and should be treated symptomatically.

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

Dogs and cats:

Do not use in pregnant or lactating dogs or cats.

Cattle: Can be used during pregnancy.

Pigs: Can be used during pregnancy and lactation.

4.8 Interaction with other medicinal products and other forms of interaction

For dogs and cats:

Other NSAIDs, diuretics, anticoagulants, aminoglycoside antibiotics and substances with high protein binding may compete for binding and thus lead to toxic effects. Meloxidolor must not be administered in conjunction with other NSAIDs or glucocorticos­teroids. Concurrent administration of potential nephrotoxic veterinary medicinal products 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 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.

For cattle and pigs:

Do not administer concurrently with glucocorticos­teroids, other non-steroidal anti-inflammatory drugs or with anticoagulant agents.

• 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 body weight (i.e. 0.4 ml/10 kg body weight).

Oral suspensions of meloxicam for dogs may be used for continuation of treatment at a dosage of 0.1 mg meloxicam/kg body weight, 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 body weight (i.e. 0.4 ml/10 kg body weight) before surgery, for example at the time of induction of anaesthesia.

Cats:

Reduction of post-operative pain:

Single subcutaneous injection at a dosage of 0.3 mg meloxicam/kg body weight (i.e. 0.06 ml/kg body weight) before surgery, for example at the time of induction of anaesthesia.

Cattle:

Single subcutaneous or intravenous injection at a dosage of 0.5 mg meloxicam/kg body weight (i.e.10 ml/100 kg body weight) in combination with antibiotic therapy or with oral re-hydration therapy, as appropriate.

Pigs:

Locomotor disorders:

Single intramuscular injection at a dosage of 0.4 mg meloxicam/kg body weight (i.e. 2 ml/25 kg body weight). If required, a second administration of meloxicam can be given after 24 hours.

Reduction of post-operative pain:

Single intramuscular injection at a dosage of 0.4 mg meloxicam/kg body weight (i.e. 0.4 ml/5 kg body weight) before surgery.

Particular care should be taken with regard to the accuracy of dosing including the use of an appropriate dosing device and careful estimation of body weight.

Avoid introduction of contamination during use. The stopper should not be punctured more than 20 times.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

In case of overdose symptomatic treatment should be initiated.

• 4.11 Withdrawal period(s)

Cattle: Meat and offal: 15 days

Pigs: Meat and offal: 5 days

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antiinflammatory 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, 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. In vitro and in vivo studies demonstrated that meloxicam inhibits cyclooxygenase-2 (COX-2) to a greater extent than cyclooxygenase-1 (COX-1). Meloxicam also has anti-endotoxic properties because it has been shown to inhibit production of thromboxane B2 induced by E. coli endotoxin administration in calves and pigs.

• 5.2 Pharmacoki­netic particulars

Absorption

Following subcutaneous administration, meloxicam is completely bioavailable and maximal mean plasma concentrations of 0.73 gg/ml in dogs and 1.1 gg/ml in cats were reached approximately 2.5 hours and 1.5 hours post administration, respectively.

After a single subcutaneous dose of 0.5 mg meloxicam/kg, Cmax values of 2.1 ^g/ml were reached after 7.7 hours in young cattle.

Following single intramuscular doses of 0.4 mg meloxicam/kg, a Cmax value of 1.1 to 1.5 ^ig/ml was reached within 1 hour in pigs.

Distribution

There is a linear relationship between the dose administered and plasma concentration observed in the therapeutic dose range in dogs and cats. 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.

In cattle and pigs, the highest meloxicam concentrations are to be found in liver and kidney. Comparatively low concentrations are detectable in skeletal muscle and fat.

Metabolism

Meloxicam is predominantly found in plasma. For dogs, cats and cattle it is also a major biliary excretion product whereas urine contains only traces of the parent compound.

In cattle, meloxicam is also a major excretion product in milk. In pigs, bile and urine contain only traces of the parent compound.

Five major metabolites were detected all having been shown to be pharmacologically inactive. Meloxicam is metabolised to an alcohol, an acid derivative and to several polar metabolites. The main pathway of meloxicam biotransformation is oxidation.

Elimination

In dogs and cats, 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 in dogs.

In cats, the detection of metabolites from the parent compound in urine and faeces, but not in plasma is indicative for their rapid excretion. 21 % of the recovered dose is eliminated in urine (2 % as unchanged meloxicam, 19 % as metabolites) and 79 % in the faeces (49 % as unchanged meloxicam, 30 % as metabolites).

Meloxicam is eliminated with a half-life of 26 hours after subcutaneous injection in young cattle. In pigs, after intramuscular administration, the mean plasma elimination half-life is approximately 2.5 hours. Approximately 50 % of the administered dose is eliminated via urine and the remainder via faeces.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Ethanol

Poloxamer 188

Sodium chloride

Glycine

Sodium hydroxide

Hydrochloric acid

Glycofurol

Meglumine

Water for injections

6.2 Major 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

Colourless type I glass vials of 10 ml, 20 ml or 100 ml, closed with a rubber stopper and sealed with an aluminium cap.

Multi-packs of 5 × 20 ml and 10 × 20 ml.

Not all pack sizes may be marketed.

• 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Le Vet Beheer B.V.

Wilgenweg 7

3421 TV Oudewater

The Netherlands

8. MARKETING AUTHORISATION NUMBERS

EU/2/13/148/001

EU/2/13/148/002

EU/2/13/148/003

EU/2/13/148/008

EU/2/13/148/009

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22/04/2013

Date of last renewal: 20/04/2018

10. DATE OF REVISION OF THE TEXT

Detailed information on this veterinary medicinal product is available on the website of the European

Medicines Agency.

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml contains:

Active substance:

Meloxicam 20 mg

Excipient:

Ethanol 150 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear yellow solution.

4. CLINICAL PARTICULARS4.1 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-metritis-agalactia 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 cases of hypersensitivity to the active substance or to any of the excipients.

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 Meloxidolor 20 minutes before dehorning reduces post-operative pain. Meloxidolor 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 case 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 give rise to 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.

The veterinary medicinal product should not be administered by pregnant women or women of childbearing potential as Meloxicam may be harmful to the foetus and unborn child.

• 4.6 Adverse reactions (frequency and seriousness)

In cattle and pigs, subcutaneous, intramuscular as well as intravenous administration is well tolerated; only a slight transient swelling at the injection site following subcutaneous administration was observed in less than 10 % of the cattle treated in clinical studies.

In horses, in rare cases a transient swelling at the injection site can occur but resolves without intervention.

In very rare cases anaphylactoid reactions, which may be serious (including fatal), may occur and should be treated symptomatically.

The frequency of adverse reactions is defined using the following convention:

• – very common (more than 1 in 10 animals treated displaying adverse reactions)

• – 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

Cattle and pigs: Can be used during pregnancy and lactation.

Horses: Do not use in pregnant or lactating mares.

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 anticoagulant 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.

Pigs:

Single intramuscular injection at a dosage of 0.4 mg meloxicam/kg body weight (i.e. 2 m l/100 kg body weight) in combination with antibiotic therapy, as appropriate. If required, a second administration of meloxicam can be given after 24 hours.

Horses:

Single intravenous injection at a dosage of 0.6 mg meloxicam/kg body weight (i.e. 3 ml/100 kg body weight).

Avoid introduction of contamination during use. The stopper should not be punctured more than 20 times.

4.10 Overdose (symptoms, emergency procedures, antidotes if necessary)

In case of overdose symptomatic treatment should be initiated.

• 4.11 Withdrawal period(s)

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: Antiinflammatory 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, 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 B2 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, Cmax values of 2.1 ^g/ml and 2.7 ^g/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 Cmax value of 1.9 ^g/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

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 PARTICULARS6.1 List of excipients

Ethanol

Poloxamer 188

Macrogol 300

Glycine

Disodium edetate

Sodium hydroxide

Hydrochloric acid

Meglumine

Water for injections

6.2 Major 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

Colourless type I glass vial containing 50 ml or 100 ml, closed with a rubber stopper and sealed with an aluminium cap.

Multi-pack of 12 × 100ml

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

7. MARKETING AUTHORISATION HOLDER

Le Vet Beheer B.V.

Wilgenweg 7

3421 TV Oudewater

The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/13/148/004

EU/2/13/148/005

EU/2/13/148/010

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22/04/2013

Date of last renewal: 20/04/2018