SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

NUFLOR 300 mg/ml solution for injection for cattle and sheep

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains

Active substance: Florfenicol 300.00 mg

Excipient(s):

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection

Clear, light yellow to straw-coloured, somewhat viscous solution

4. CLINICAL PARTICULARS

4.1 Target species

Cattle and sheep

4.2 Indications for use, specifying the target species

Cattle:

Diseases caused by florfenicol susceptible bacteria.

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

Sheep:

Treatment of ovine respiratory tract infections due to Mannheimia haemolytica andPasteurella multocida susceptible to florfenicol.

4.3 Contraindications

Do not use in adult bulls and rams intended for breeding purposes.

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

4.4 Special warnings for each target species

Do not exceed the recommended treatment dose or the recommended duration of treatment.

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.

The safety of the product has not been established in sheep under 7 weeks of age.

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

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

Care should be taken to avoid accidental self-injection.

4.6 Adverse reactions (frequency and seriousness)

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 and subcutaneous routes may cause inflammatory lesions at injection site which persist for 14 days.

In very rare cases, anaphylactic shocks have been reported in bovines.

Sheep:

A decrease in food consumption 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 inflammatory lesions at the injection site which may persist up to 28 days. Typically, these are mild and transient.

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 and ovine 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

No data available.

4.9 Amounts to be administered and administration route

For treatment

Cattle:

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

SC route: 40 mg/kg bodyweight (2ml/15kg) 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.

Sheep:

20 mg florfenicol/kg bodyweight (1 ml/15 kg bodyweight) by intramuscular injection daily for three consecutive days. The volume administered per injection site should not exceed 4 ml.

Pharmacokinetic studies showed that mean plasma concentrations remain above MIC₉₀(1 g/ml) for up to 18 hours after administration of the product at the recommended treatment dose. The pre-clinical data provided support the recommended treatment interval (24 hours) for target pathogens with MIC up to 1 g/ml.

For prevention

Cattle:

SC route: 40 mg/kg bodyweight (2ml/15kg) 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.

Swab septum before removing each dose. Use a dry sterile needle and syringe.

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

As the vial should not be broached more than 20 times, the user should select the most appropriate vial size according to the target species to be treated. When treating groups of animals in one run, use a draw-of needle that has been placed in the vial stopper to avoid excess broaching of the stopper. The draw-of needle should be removed after treatment.

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

In 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.

In sheep after administration of 3 times the recommended dose or more a transient reduction in feed and water consumption has been observed. Additional secondary effects that were noted included an increased incidence of lethargy, emaciation and loose faeces.

Head tilt was seen after administration of 5 times the recommended dose and was considered most likely a result of irritation at the injection site.

4.11 Withdrawal period(s)

Meat and offal:

Cattle: by IM (at 20 mg/kg bodyweight, twice): 30 days

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

Sheep: 39 days

Milk: Not permitted for use in lactating animals producing milk for human consumption including pregnant animals intended to produce milk for human consumption.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antibacterial for systemic use (Amphenicols)

ATCVet code: QJ01BA90

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. Laboratory tests have shown that florfenicol is active against the most commonly isolated bacterial pathogens involved in ovine and bovine respiratory disease which include Mannheimia haemolytica, Pasteurella multocida, and,for cattle Histophilus somni.

Florfenicol is considered to be a bacteriostatic agent, but in vitrostudies of florfenicol demonstrate bactericidal activity againstMannheimia haemolytica, Pasteurella multocida andHistophilus somni.

MIC data for the target pathogens are presented in the table below:

Species	Range (µg/ml)	MIC50 (µg/ml)	MIC90 (µg/ml)
Mannheimia haemolytica (n=151)	0.25-2	1	1
Pasteurella multocida (n=88)	0.25-0.5	0.5	0.5

Strains were isolated from sheep suffering from respiratory tract infection in Germany, United Kingdom, Spain and France between 2006 and 2010.

Cattle:

Intramuscular administration at the recommended dose of 20 mg/kg maintains efficacious blood levels in cattle for 48 hours. Maximum mean serum concentration (C_max) of 3.37 µg/ml occurs at 3.3 hours (T_max) after dosing.

The mean serum concentration 24 hours after dosing was 0.77 µg/ml.

The administration of the product by subcutaneous route at the recommended dosage of 40mg/kg maintains bovine efficacious blood levels in cattle (ie above the MIC₉₀of the main respiratory pathogens) for 63 hours. Maximum serum concentration (C_max) of approximately 5 µg/ml occurs approximately 5.3 hours (T_max) after dosing. The mean serum concentration 24 hours after dosing is approximately 2 µg/ml.

The harmonic mean elimination half life was 18.3 hours.

Sheep:

After initial intramuscular administration of florfenicol (20 mg/kg), the mean maximum serum concentration of 10.0 g/ml is reached after 1 hours. Following the third intramuscular administration, the maximum serum concentration of 11.3 g/ml is reached after 1.5 hours. The elimination half-life was estimated to be 13.76 + 6.42h. Bioavailability is about 90 %.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

N-methyl-2-pyrollidone

Propylene glycol

Macrogol 300

6.2 Incompatibilities

Do not mix the product with other medicinal products.

6.3 Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale: 2 years

Shelf life after first broaching the immediate packaging: 28 days

6.4. Special precautions for storage

Do not store above 25°C.

Do not refrigerate.

Protect from frost.

6.5 Nature and composition of immediate packaging

50, 100 and 250 ml colourless Type I glass vials closed with bromobutyl rubber stoppers with aluminium seals.

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 medicinalproduct or waste materials derived from such

veterinary medicinal productsshould 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

Vm 01708/4574

9. DATE OF FIRST AUTHORISATION

25 February 2013

10. DATE OF REVISION OF THE TEXT

February 2013

Approved: 25/02/2013