SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Nuflor Minidose 450 mg/ml solution for injection for cattle

ES: Flomac 450 mg/ml solution for injection for cattle

FI: Nuflor vet Minidose 450 mg/ml solution for injection for cattle

FR: Nuflor 450 mg/ml solution for injection for cattle

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substance:

Florfenicol…………………………..450.00 mg

Excipients:

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Clear colourless to yellow solution for injection

4. CLINICAL PARTICULARS

4.1 Target species

Cattle

4.2 Indications for use, specifying the target species

Preventive and therapeutic treatment of respiratory tract infections in cattle due to Mannheimia haemolytica, Pasteurella multocidaand Histophilus somnisusceptible to florfenicol. The presence of the disease in the herd should be confirmed before administering preventive treatment.

4.3 Contraindications

Do not use in adult bulls intended for breeding purposes.

Do not use in case of known 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:

The product should be used in conjunction with susceptibility testing and take into account official and local antimicrobial policies.

Do not use where resistance to florfenicol or other amphenicols is known to occur. Inappropriate use of the veterinary medicinal product may increase the prevalence of bacteria resistant to florfenicol and other amphenicols.

The prolonged or repeated use of the veterinary medicinal product should be avoided by

improving farming management practices, cleaning and disinfection measures and eliminating any stress condition.

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 self-injection, seek medical advice immediately and show the package leaflet or the label to the physician. Avoid direct contact with skin, mouth and eyes. Wash hands after treatment.

4.6 Adverse reactions (frequency and seriousness)

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.

Subcutaneous injection of the product at the maximum recommended volume of 10 mL per injection site may cause transient local algesia and clinically obvious swelling at the injection site. Local algesia may persist for some days. Injection site swellings decrease over time but may persist for up to 61 days.

Intramuscular injection of the product at the maximum recommended volume of 10 mL per injection site may cause transient local algesia and clinically obvious swelling at the injection site.Local algesia may persist for some days. Injection site swellings decrease over time but may persist for up to 24 days. Inflammatory lesions at the injection site (seen at necropsy) may persist for 37 days after injection.

4.7 Use during pregnancy, lactation or lay

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

However, 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

SC route: 40 mg/kg body weight (4 ml/45 kg) to be administered once only.

IM route: 20 mg/kg body weight (2 ml/45 kg) to be administered twice 48 hours apart.

The injection should only be given in the neck. The dose volume given at any one injection site should not exceed 10 ml.

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

Swab septum before removing each dose. Use a dry, sterile needle and syringe.
For 250 ml vials, do not broach the vial more than 25 times.

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

No data available. .

4.11 Withdrawal periods

Meat and offal:

by SC (at 40 mg/kg body weight, once): 64 days

by IM (at 20 mg/kg bodyweight, twice): 37 days

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 and time-dependent. Laboratory tests have shown that florfenicol is active against the most commonly isolated bacterial pathogens involved in bovine respiratory disease which include Mannheimia haemolytica, Pasteurella multocidaand Histophilus somni.

Florfenicol is considered to be a bacteriostatic agent, but in vitro studies of florfenicol demonstrate bactericidal activity against Mannheimia haemolytica, Pasteurella multocidaand Histophilus somni.

For Mannheimia haemolytica, Pasteurella multocidaand Histophilus somnithe following breakpoints have been determined for florfenicol in bovine respiratory disease: susceptible: ≤2 µg/ml, intermediate: 4 µg/ml, resistant: ≥8 µg/ml.

Resistance to florfenicol is mainly mediated by an efflux system due to specific (flo-R) or multidrug transporters (AcrAB-TolC). The genes corresponding to these mechanisms are coded on mobile genetic elements such as plasmids, transposons or genes cassettes.

Surveillance data of the susceptibility of target field isolates from cattle collected between 1995 and 2009 across Europe show a constant activity of florfenicol with no finding of resistant isolates. In the recent literature, one resistant isolate of P. multocidawas reported from a calf in Germany in 2007 harbouring a plasmid mediated flo-R. No co-resistance to other antibiotic families was observed. Cross-resistance with chloramphenicol can occur.

Resistance to florfenicol and other antimicrobials has been identified in the food-borne pathogen Salmonella typhimurium and co-resistance with the third-generation cephalosporins has been observed inrespiratory and digestiveEscherichia Coli.This has not been observed for the target pathogens.

5.2 Pharmacokinetic particulars

After parenteral application florfenicol is mainly excreted via urine and to a small extent via faeces, mainly as parent compound but also followed by florfenicol amine and florfenicol oxamic acid.

The administration of the product by the subcutaneous route at the recommended dose of 40 mg/kg maintained efficacious plasma levels of florfenicol in cattle above the MIC₉₀of 0.5 µg/ml and 1.0 µg/ml for 90.7 hours and 33.8 hours, respectively. Maximum mean serum concentration (Cmax) of 1.8 µg/ml occurred 7 hours (Tmax) after dosing.

The administration of the product by the intramuscular route at the recommended dose of 20 mg/kg maintained efficacious plasma levels of florfenicol in cattle above the MIC₉₀of 0.5 µg/ml and 1.0 µg/ml for 48.7 hours and 30.3 hours, respectively. Maximum mean serum concentration (Cmax) of 3.0 µg/ml occurred 6 hours (Tmax) after dosing.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

N-Methylpyrrolidone

Diethylene glycol monoethyl ether

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: 2 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 temperature storage conditions.

Keep the vial in the outer carton in order to protect from light.

6.5 Nature and composition of immediate packaging

50, 100 and 250 ml colourless type II glass multiple dose vials, sealed with bromobutyl rubber stopperssecured with aluminium overseal.

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

Intervet UK Ltd

Walton Manor

Walton

Milton Keynes

Buckinghamshire

MK7 7AJ

8. MARKETING AUTHORISATION NUMBER

Vm01708/4541

9. DATE OF FIRST AUTHORISATION

Date:03 October 2008

10. DATE OF REVISION OF THE TEXT

Date:December 2013

PROHIBITION OF SALE, SUPPLY AND/OR USE

To be supplied only on veterinary prescription

Approved: 23/12/2013