Daxocox - summary of medicine characteristics

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Daxocox 15 mg tablets for dogs

Daxocox 30 mg tablets for dogs

Daxocox 45 mg tablets for dogs

Daxocox 70 mg tablets for dogs

Daxocox 100 mg tablets for dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains:

Active substance:

Enflicoxib Enflicoxib Enflicoxib Enflicoxib Enflicoxib

Excipients:

Iron oxide black (E172)

Iron oxide yellow (E172)

Iron oxide red (E172)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablets

Brown, round and convex tablets.

4. CLINICAL PARTICULARS4.1 Target species

Dogs

• 4.2 Indications for use, specifying the target species

For the treatment of pain and inflammation associated with osteoarthritis (or degenerative joint disease) in dogs.

4.3 Contraindications

Do not use in animals suffering from gastrointestinal disorders, protein or blood losing enteropathy or haemorrhagic disorders.

Do not use in cases of impaired renal or hepatic function.

Do not use in cases of cardiac insufficiency.

Do not use in pregnant or lactating dogs.

Do not use in animals intended for breeding purposes.

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

Do not use in cases of known hypersensitivity to sulphonamides.

Do not use in any dehydrated, hypovolemic or hypotensive animal, as there is a potential risk of increased renal toxicity.

• 4.4 Special warnings for each target species

Do not administer other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or glucocorticoids concurrently or within 2 weeks of the last administration of this veterinary medicinal product.

• 4.5 Special precautions for use

Special precautions for use in animals

Since the safety of the medicinal product has not been fully demonstrated in very young animals, careful monitoring is advised during the treatment of young dogs aged less than 6 months.

The active metabolite of enflicoxib exhibits an extended plasma half-life due to its low rate of elimination. Use this veterinary medicinal product under strict veterinary monitoring where there is a risk of gastrointestinal ulceration, or if the animal previously displayed intolerance to NSAIDs.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

This veterinary medicinal product can cause hypersensitivity (allergic) reactions. People with known hypersensitivity to NSAIDs should avoid contact with the veterinary medicinal product.

Some NSAIDs may be harmful for the unborn child, especially during the third trimester of pregnancy. Pregnant women should administer this veterinary medicinal product with care.

Ingestion of this veterinary medicinal product may be harmful, especially for children, and prolonged pharmacological effects leading to e.g. gastrointestinal disorders may be observed. To avoid accidental ingestion, administer the tablet to the dog immediately after removal from the blister packaging and do not split or crush tablets.

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)

Vomiting, soft faeces and/or diarrhoea have been commonly reported in clinical trials, but most cases recovered without treatment.

Apathy, loss of appetite or haemorrhagic diarrhoea have been reported in uncommon cases. Gastrointestinal ulceration has been reported in uncommon cases.

Elevated blood urea and serum cholesterol levels were observed in healthy, young dogs at the recommended dose in a laboratory safety study.

In case of adverse reactions the use of the veterinary medicinal product should be stopped and general supportive therapy, as for clinical overdose with NSAIDs, should be applied until complete resolution of the signs. Particular attention should be paid to maintain haemodynamic status.

Gastrointestinal protectants and parenteral fluids, as appropriate, may be required for animals that experience gastrointestinal or renal adverse reactions.

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

Laboratory studies in rats and rabbits have shown evidence of foetotoxic effects at maternally toxic doses.

The safety of this veterinary medicinal product has not been established during pregnancy, lactation or reproduction in the target species. Do not use in pregnant, lactating or breeding dogs.

4.8 Interaction with other medicinal products and other forms of interaction

No drug-interaction studies have been performed. In common with other NSAIDs, this veterinary medicinal product should not be administered simultaneously with other NSAIDs or glucocorticoids.

Animals should be carefully monitored if this veterinary medicinal product is administered simultaneously with an anticoagulant.

Enflicoxib is highly bound to plasma proteins and may compete with other highly bound substances, such that concomitant administration may result in toxic effects.

Pre-treatment with other anti-inflammatory substances may result in additional or increased adverse reactions. To avoid such adverse reactions when this veterinary medicinal product is to be administered in replacement to another NSAID, ensure an appropriate treatment-free period before administering the first dose. The treatment-free period should, however, consider the pharmacology of the medicinal products previously used.

Concurrent administration of potentially nephrotoxic veterinary medicinal products should be avoided.

• 4.9 Amounts to be administered and administration route

Oral use.

Dosing interval is ONCE PER WEEK.

First dose: 8 mg enflicoxib per kg body weight.

Maintenance dose: repeat the treatment every 7 days at the dose of 4 mg enflicoxib per kg body weight.

The veterinary medicinal product should be given immediately before or with the dog’s meal. The bodyweight of animals to be treated should be accurately determined to ensure administration of the correct dose.

Number of tablets to be administered

FIRST DOSE

MAINTENANCE DOSE

8 mg/kg

4 mg/kg

Body weight (Kg) /Tablet size (mg)	15 mg	30 mg	45 mg	70 mg	100 mg	15 mg	30 mg	45 mg	70 mg	100 mg
3 – 4.9	2					1
5 – 7.5		2					1
7.6 – 11.2			2					1
11.3 – 15		4					2
15.1 – 17.5				2					1
17.6 – 25					2					1
25.1 – 35				4					2
35.1 – 50					4					2
50.1 – 75					6					3

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

In overdose safety studies at a continuous weekly administration at 12 mg/kg body weight for a period of 7 months and at 20 mg/kg body weight for a period of 3 months, with an initial loading dose, there was evidence of elevated blood urea and serum cholesterol levels. No other associated treatment related effects were detected.

• 4.11 Withdrawal period

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products, non-steroids, Coxibs. ATCvet code: QM01AH95 enflicoxib

5.1 Pharmacodynamic properties

Enflicoxib is a non-steroidal anti-inflammatory drug belonging to the coxib class and acting by selective inhibition of the enzyme cyclooxygenase 2. The cyclooxygenase enzyme (COX) is present in two isoforms. COX-1 is usually a constitutive enzyme expressed in tissues, which synthesize products responsible for normal physiologic functions (e.g. in the gastro-intestinal tract and kidneys), and COX-2 is mainly inducible and synthesized by macrophages and other inflammatory cells after stimulation by cytokines and other mediators of inflammation. COX-2 is involved in the production of mediators, including PGE2, that induce pain, exudation, inflammation and fever.

• 5.2 Pharmacoki­netic particulars

Enflicoxib is well absorbed after oral administration; bioavailability is high, and it is increased by 40–50% with food. The recommended dose is based on administration with food. After oral administration to fed dogs at the recommended loading dose of 8 mg/kg bw, enflicoxib is readily absorbed and reaches its maximal concentration of 1.8 (± 0.4) ^g/ml (Cmax) after 2 hours (Tmax). The elimination half-life (t1/2) is 20 h.

Enflicoxib is extensively transformed by the hepatic microsomal system into an active pyrazol metabolite, which reaches its maximal concentration of 1.3 (± 0.2) ^g/ml (Cmax) after 6 days (Tmax). The elimination half-life (t1/2) is 17 days.

Enflicoxib and its active metabolite are extensively bound to dog plasma proteins (98–99%) and are mainly excreted in faeces by the biliary route and, to a lesser extent, in urine.

After repeated administrations, systemic exposure to enflicoxib and its pyrazol metabolite rapidly reaches a plateau, with no evidence of time-dependent pharmacokinetics or over-accumulation for either compound.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Mannitol

Silicified microcrystalline cellulose

Sodium laurilsulfate

Crospovidone

Copovidone

Sodium stearyl fumarate

Talc

Iron oxide black (E172)

Iron oxide yellow (E172)

Iron oxide red (E172)

Microcrystalline cellulose

Dried flavour

6.2 Major incompatibilities

Not applicable.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 30 months

6.4. Special precautions for storage

This veterinary medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from light.

In order to avoid any accidental ingestion, store tablets out of reach of animals.

• 6.5 Nature and composition of immediate packaging

Blisters are made of a PVC/Aluminium/o­riented polyamide blister foil and an aluminium lidding foil.

Package sizes:

Carton boxes containing 4, 10, 12, 20, 24, 50 or 100 tablets.

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

7. MARKETING AUTHORISATION HOLDER

Ecuphar NV

Legeweg 157-i

B-8020

Oostkamp

Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/21/270/001–035

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: {DD/MM/YYYY}