SUMMARY OF PTODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Enrox Flavour 50 mg Tablets for dogs (United Kingdom, Austria, Belgium, Germany, Denmark, Greece, Ireland, Italy, Luxembourg, Netherlands)

Enrox Sabor 50 mg Tablets for dogs (Spain, Portugal)

Enroxil Flavour 50 mg Tablets for dogs (Bulgaria, Czech Republic, Hungary, Lithuania, Latvia, Poland, Romania, Slovenia, Slovakia)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains:

Active substance:

Enrofloxacin 50 mg

Excipients:

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet.

Round slightly biconvex, cream to light brownish tablets with possible visible white or darker spots, one side scored and bevel-edged. The tablets can be divided into equal halves.

4. CLINICAL PARTICULARS

4.1 Target species

Dogs.

4.2 Indications for use, specifying the target species

The product is for use in dogs for the treatment of bacterial infections of the alimentary, respiratory and urogenital tracts, skin, secondary wound infections and otitis externa where clinical experience, supported where possible by sensitivity testing of the causal organism, indicates enrofloxacin as the drug of choice.

4.3 Contraindications

Do not use in dogs less than 1 year of age or in exceptionally large breeds of dog with a longer growth period less than 18 months of age, as articular cartilage may be affected during the period of rapid growth.

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

Do not use in dogs having seizure disorders, since enrofloxacin may cause CNS stimulation.

Do not use for prophylaxis.

4.4 Special warnings for each target species

Please see point 4.3.

4.5 Special precautions for use

i) Special precautions for use in animals

Fluoroquinolones should be reserved for the treatment of clinical conditions

which have responded poorly, or are expected to respond poorly to other classes of antimicrobials. Whenever possible, use of fluoroquinolones should be based on susceptibility testing. Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to the fluoroquinolones and may decrease the effectiveness of treatment with other quinolones due to the potential for cross-resistance. Official and local antimicrobial policies should be taken into account when the product is used.

Do not use in case of resistance to quinolones, as there exists almost complete cross resistance to other quinolones and complete cross resistance to other fluoroquinolones.

Do not exceed the recommended dosage.

Use the product with caution in dogs with severe renal or hepatic impairment.

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

Wash hands after use.

In case of contact with the eyes, wash with plenty of clean water.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

People with known hypersensitivity to (fluoro)quinolones should avoid contact with the product.

4.6 Adverse reactions (frequency and seriousness)

During the period of rapid growth, enrofloxacin may affect articular cartilage development.

In very rare cases (less than 1 animal in 10,000 animals, including isolated reports) vomiting and anorexia are observed

4.7 Use during pregnancy, lactation or lay

As enrofloxacin passes into maternal milk, use only according to the benefit/risk assessment by the responsible veterinarian.

4.8 Interaction with other medicinal products and other forms of interaction

Do not combine with tetracyclines, phenicols or macrolides because of potential antagonistic effects.

Concurrent administration of fluoroquinolones may increase the action of oral anticoagulants.

Do not combine with theophylline as this could lead to a prolonged elimination of this substance.

Concurrent administration of magnesium or aluminum containing substances may be followed by retarded absorption of enrofloxacin.

4.9 Amounts to be administered and administration route

Do not exceed the recommended dose. The dosage rate of enrofloxacin is 5 mg/kg given orally once daily or as a divided dose twice daily for 5 to 10 days with or without food.

The duration of treatment in dogs may be extended depending on the clinical response and the judgement of the responsible veterinary surgeon.

To ensure a correct dosage body weight should be determined as accurately as possible to avoid underdosing.

The daily dose is achieved as follows:

Medium dogs: one tablet per 10 kg body weight.

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

In accidental overdose vomiting, diarrhoea and CNS/behavioural changes may occur. There is no antidote and treatment should be symptomatic. If necessary, administration of aluminium- or magnesium-containing antacids or activated carbon can be used to reduce absorption of enrofloxacin.

4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antibacterials for systemic use, quinolone and quinoxaline antibacterials, fluoroquinolones.

ATCvet code: QJ01MA90

Enrofloxacin is bactericidal in action with activity against Gram positive and Gram negative bacteria and mycoplasmas. The mechanism of action of the quinolones is unique among antimicrobials – they act primarily to inhibit bacterial DNA gyrase, an enzyme responsible for controlling the super coiling of bacterial DNA during replication. Resealing of the double standard helix is inhibited resulting in irreversible degradation of the chromosomal DNA. The fluoroquinolones also possess activity against bacteria in the stationary phase by an alteration of the permeability of the outher membrane phospholipid cell wall.

Susceptibility of selected canine pathogens (MIC) is as follows:

• Pasteurella multocida: 0.03 mg/L;

• Escherichia coli: 0.03-0.06 mg/L;

• Staphylococcus pseudointermedius: 0.125 mg/L;

• Pseudomonas aeruginosa: 2.0 mg/L.

Susceptibility breakpoints are: sensitive ≤0.5 mg/L; intermediate 1-2 mg/L; resistant ≥4 mg/L.

Bacterial resistance to fluoroquinolones most commonly occurs by alteration of the target, DNA-gyrase, via mutation. Less commonly mutation occurs at the topoisomerase-IV target. Other mechanisms of resistance occur when bacteria decrease the ability of the drug to enter the cell or increase active transport out of the cell. Resistance is usually chromosomally developed and, therefore, remains after antimicrobial therapy ends.Cross-resistance of enrofloxacin with other fluoroquinolones can occur. Changes in levels of resistance to fluoroquinolones over time by Campylobacter and Salmonella species are being monitored because of their possible impact on human health.

The pharmacokinetics of enrofloxacin in dogs is such that oral and parenteral administration leads to similar serum levels.

Enrofloxacin is rapidly absorbed after oral, intramuscular and subcutaneous administration.

In the study conducted in dogs the dose of enrofloxacin administered was 4.91 mg /kg. The maximal plasma concentration was 1179.94±260,83 ng/mL, Tmax was 1.57±0.62 h, half life 3,78 h (harmonic mean) and AUC_tot value 4037±1155.82 ngh/mL.

Approximately 40% of the oral or intravenous enrofloxacin dose administered in dogsis metabolised to ciprofloxacin.

The mean maximal concentration for ciprofloxacin reached 491.99±57.95 ng/mL, tmax 1.79±2.6 h and the apparent terminal half life was 5.10 h (harmonic mean). The mean AUC_tot for ciprofloxacin was 3737.21±562.65 ngh/mL.

Enrofloxacin possesses a high distribution volume. Tissue levels 2-3 times higher than that found in the serum, have been demonstrated in laboratory animals and target species. Organs in which high levels can be expected are the lungs, liver, kidney, skin, bone and lymphatic system. Enrofloxacin also distributes into the cerobrospinal fluid, the aqueous humour and the foetus in pregnant animals.

The elimination of enrofloxacin is renal, primarily through glomerular filtration and tubular secretion.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol

Maize starch

Sodium starch glycolate (type A)

Meat flavour 10022

Sodium laurilsulphate

Basic butylated methacrylate copolymer

Dibutyl sebacate

Croscarmellose sodium

Silica, colloidal anhydrous

Talc

Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale: 3 years.

Return any halved tablet to the opened strip-pack and use within 24 hours.

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

Polyamide/Aluminium/Polyvinyl chloride film (OPA/Al/PVC), heat sealed with aluminium foil containing 10 tablets / blister. Each cardboard carton contains 100 tablets in 10 blister packs.

Polyamide/Aluminium/Polyvinyl chloride film (OPA/Al/PVC), heat sealed with aluminium foil containing 10 tablets / blister. Each cardboard carton contains 10 tablets in 1 blister pack.

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

KRKA, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

8. MARKETING AUTHORISATION NUMBER

Vm01656/4008

9. DATE OF FIRST AUTHORISATION

18 June 2009

10. DATE OF REVISION OF THE TEXT

May 2014

Approved: 22/05/2014