SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

KEFLORIL 300 mg/ml Solution for injection for cattle and pigs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substance:

Florfenicol…………300 mg

Excipients

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Light yellow to yellow, clear viscous liquid.

4. CLINICAL PARTICULARS

4.1 Target species

Pigs and cattle.

4.2 Indications for use, specifying the target species

Pigs: treatment of acute outbreaks of respiratory disease caused by strains of Actinobacillus pleuropneumoniae and Pasteurella multocidasusceptible to florfenicol.

Cattle: diseases caused by florfenicol susceptible bacteria.

Preventive and therapeutic treatment of respiratory tract infections in cattle due to Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. The presence of the disease in the herd should be established before preventive treatment.

4.3 Contraindications

Do not administer to boars and adult bulls intended for breeding purposes.

Do not use in cases of known hypersensitivity to the active ingredient 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

Swab the stopper before removing each dose. Use a dry, sterile syringe and needle.

Do not use in piglets of less than 2 kg.

Use of product should be based on susceptibility testing of the bacteria isolated from the animal. If this is not possible, therapy should be based on local (regional, farm level) epidemiological information about susceptibility of the target bacteria.

Official national and regional antimicrobial policies should be taken into account when the product is used.

Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to the florfenicol and may decrease the effectiveness of treatment with other antimicrobials, due to the potential for cross-resistance.

Use a suitable draw-off needle or automatic dosing syringe to avoid excessive puncturing of the closure.

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

Care should be taken to avoid accidental self-injection.

In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician.’

Do not use the product in known cases of sensitivity to propylene glycol and polyethylene glycols.

Avoid direct contact with skin, eyes or mouth.

In case of accidental spillage of the solution onto skin, wash off immediately with soap and water.

In case of accidental contact with eyes, rinse immediately with plenty of water.

4.6 Adverse reactions (frequency and seriousness)

Pigs

Commonly observed adverse effects are transient diarrhoea and/or peri-anal and rectal erythema/ oedema which may affect 50% of the animals. These effects can be observed for one week.

Transient swelling lasting up to 5 days may be observed at the site of injection. Inflammatory lesions at the injection site may be seen up to 28 days.

Cattle

A decrease in food consumption and transient softening of the faeces may occur during the treatment period. The treated animals recover quickly and completely upon termination of treatment.

Administration of the product by the intramuscular route may cause swelling at the injection site which may persist for 14 days. Inflammation at the injection site may persist up to 32 days after administration.

Administration of the product by the subcutaneous route may cause swelling and inflammation at the injection site which may persist at least for 41 days.

4.7 Use during pregnancy, lactation or lay

Studies in laboratory animals have not revealed any evidence of embryo- or foetotoxic potential for florfenicol.

Pigs: the safety of the product in sows during pregnancy and lactation has not been demonstrated. Use of the product during pregnancy and lactation is therefore not recommended.

Cattle: the effect of florfenicol on bovine reproductive performance and pregnancy has not been assessed. Use only accordingly to the benefit/risk assessment by the responsible veterinarian.

4.8 Interaction with other medicinal products and other forms of interaction

None known.

4.9 Amounts to be administered and administration route

Pigs

15 mg/kg bodyweight (1 ml per 20 kg) by intramuscular injection into the neck muscle twice at

48-hour intervals using a dry, sterile 16-gauge needle.

The volume administered per injection site should not exceed 3 ml.

It is recommended to treat animals in the early stages of disease and to evaluate the response to treatment within 48 hours after the second injection.

If clinical signs of respiratory disease persist 48 hours after the last injection, treatment should be changed using another formulation or another antibiotic and continued until clinical signs have resolved.

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

Cattle

For treatment:

IM route: 20 mg/kg bodyweight (1 ml/15 kg) to be administered twice 48 hours apart using a 16 gauge needle.

SC route: 40 mg/kg bodyweight (2 ml/15 kg) to be administered once only using a 16 gauge needle. The dose volume given at any one injection site should not exceed 10 ml.

The injection should only be given in the neck.

For prevention:

SC route: 40 mg/kg bodyweight (2 ml/15 kg) to be administered once only using a 16 gauge needle. The dose volume given at any one injection site should not exceed 10 ml.

The injection should only be given in the neck.

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

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

Pigs

After administration of 3 times the recommended dose or more a reduction in feeding, hydration and weight gain has been observed.

After administration of 5 times the recommended dose or more vomiting has also been noted.

Cattle

No other symptoms than those mentioned in section 4.6 are expected.

4.11 Withdrawal period(s)

Pigs

Meat and offal: 18 days

Cattle

Meat and offal: by IM (at 20 mg/kg bodyweight, twice): 30 days

by SC (at 40 mg/kg bodyweight, once): 44 days

Milk: Not permitted for use in lactating animals producing milk for human consumption.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antibacterials for systemic use

ATCvet code: QJ01BA90

5.1 Pharmacodynamic properties

Florfenicol is a synthetic broad spectrum antibiotic effective against most Gram-positive and Gram-negative bacteria isolated from domestic animals. Florfenicol acts by inhibiting protein synthesis at the ribosomal level and is bacteriostatic. However, bactericidal activity has been demonstrated in-vitro against Actinobacillus pleuropneumoniae, Pasteurella multocida, Mannheimia haemolytica and Histophilus somni.

In-vitro testing has shown that florfenicol is active against the bacterial pathogens most commonly isolated in respiratory diseases in pigs, including Actinobacillus pleuropneumoniae and Pasteurella multocida. Laboratory tests have also shown that florfenicol is active against the most commonly isolated bacterial pathogens involved in bovine respiratory disease which include Mannheimia haemolytica, Pasteurella multocida andHistophilus somni.

Acquired resistance to florfenicol is mediated by efflux pump resistance associated with a floR gene. Such resistance has not yet been identified in the target pathogens except for Pasteurella multocida.Cross resistance with chloramphenicol can occur.

Resistance to florfenicol and other antimicrobials has been identified in the food-borne pathogen Salmonella typhimurium.

5.2 Pharmacokinetic particulars

Cattle

Intramuscular administration at the recommended dose of 20 mg/kg maintains efficacious blood levels in cattle for 48 hours. Maximum mean plasma concentration (Cmax) of 3.86 μg/ml occurs at 5 hours (Tmax) after dosing. The mean plasma concentration 24 hours after dosing was 1.56 μg/ml.

After subcutaneous administration of the recommended dose of 40 mg florfenicol/kg b.w., maximum plasma concentration (Cmax) of approximately 3.5 μg/ml occurs approximately 7.0 hours (Tmax) after dosing. The mean plasma concentration 24 hours after dosing is approximately 2 μg/ml.

The harmonic mean elimination half-life was 18.8 hours.

Pigs

After single intramuscular administration of the recommended dose of 15mg/kg to pigs maximum mean plasma concentration (Cmax) of 2.8 μg/ml occurs at 2 hours (Tmax) after dosing.

After administration to pigs by the intramuscular route, florfenicol is rapidly excreted, primarily in urine. Florfenicol is extensively metabolised.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Dimethyl sulfoxide

Propylene glycol

Macrogol 400

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

50, 100 and 250 ml Type I amber glass bottle closed with a bromobutyl rubber stopper and aluminium seal.

1 bottle (50 ml) in cardboard box.

1 bottle (100 ml) in cardboard box.

1 bottle (250 ml) in cardboard box.

Not all pack sizes may be marketed.

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

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

7. MARKETING AUTHORISATION HOLDER

Vetoquinol UK Ltd

Vetoquinol House

Great Slade

Buckingham Industrial Park

Buckingham

Buckinghamshire

MK18 1PA

8. MARKETING AUTHORISATION NUMBER

Vm 08007/4123

9. DATE OF FIRST AUTHORISATION

15 September 2010

10. DATE OF REVISION OF THE TEXT

July 2015

Approved: 14 July 2015