SUMMARY OF PRODUCT CHARACTERISTICS: 1. NAME OF THE VETERINARY MEDICINAL PRODUCT: Forcyl 160 mg/ml solution for injection for cattle 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains: Active substance: Marbofloxacin 160 mg Excipients: Benzyl alcohol (E 1519) 15 mg. For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM: Solution for injection. Clear yellow greenish to yellow brownish solution. 4. CLINICAL PARTICULARS: 4.1 Target species: Cattle. 4.2. Indications for use, specifying the target species. In cattle: - Therapeutic treatment of respiratory infections caused by sensitive strains of Pasteurella multocida and Mannheimia haemolytica. In lactating cows: - Treatment of acute mastitis caused by sensitive strains of Escherichia coli. 4.3 Contraindications: Do not use in animals with known hypersensitivity to fluoroquinolones or to any of the excipients. Do not use in cases where the pathogen involved is resistant to other fluoroquinolones (cross resistance). 4.4. Special warnings: The efficacy of the product has not been tested on mastitis caused by Gram positive bacteria. 4.5 Special precautions for use: Special precautions for use in animals: Official and local antimicrobial policies should be taken into account when this product is used. 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. Wherever possible, use of the product should only 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. Special precautions to be taken by the person administering the veterinary medicinal product to animals: People with known hypersensitivity to (fluoro)quinolones should avoid any contact with the product. If the product comes into contact with the skin or eyes, rinse with copious amounts of water. Care should be taken to avoid accidental self-injection. In the event of accidental self-administration, the user should immediately seek professional medical care. Accidental self-injection can induce a slight irritation. Other precautions: None. 4.6 Adverse reactions (frequency and seriousness): Administration by the intramuscular route may cause rare transient local reactions such as pain and swelling at the injection site which may persist up to 7 days after injection. Fluoroquinolones are known to induce arthropathies. In cattle, such lesions were observed after three days treatment with the 16% marbofloxacin solution. These lesions did not induce clinical signs and should be reversible, particularly if they were to be observed after a single administration. No other adverse effect was observed on cattle. 4.7 Use during pregnancy, lactation or lay: Studies in laboratory animals (rats, rabbits) did not show any evidence of a teratogenic, embryotoxic or maternotoxic effect associated with the use of marbofloxacin. Safety of the product at 10 mg/kg has not been determined in pregnant cows or in suckling calves when used in cows. Use therefore according to the benefit/risk assessment carried out 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: - Therapeutic treatment of respiratory infections 10 mg/kg body weight i.e. 10 ml /160 kg body weight in a single intramuscular injection. - Treatment of acute mastitis caused by sensitive strains of Escherichia coli 10 mg/kg body weight i.e. 10 ml/160 kg body weight in a single intramuscular or intravenous injection. If the volume to be injected intramuscularly is more than 20 ml, it should be divided between two or more injection sites. To ensure a correct dosage, bodyweight should be determined as accurately as possible to avoid underdosing. Where there is slight cloudiness or visible particles present, such cloudiness or particles disappear when the bottle is shaken before use. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary: Lesions of the joint cartilage were observed in some animals treated at 10 mg/kg or 30 mg/kg for three times the recommended treatment duration, but did not induce clinical signs. Moreover, no sign of overdosage was observed throughout this study. Overdosage may cause signs such as acute neurological disorders which should be treated symptomatically. 4.11 Withdrawal period(s): Meat and offal: 5 days. Milk : 48 hours. 5. PHARMACOLOGICAL PROPERTIES: ATC Vet code: QJ01MA93. Pharmacotherapeutic group: antibacterials for systemic use, Fluoroquinolones. 5.1 Pharmacodynamic properties: Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group, which acts by inhibition of DNA gyrase. The in vitro activity of marbofloxacin has been demonstrated towards Pasteurella multocida, Mannheimia haemolytica and Escherichia coli. The marbofloxacin in vitro activity against pathogens isolated in 2007 from bovine respiratory diseases is good: MIC values are comprised between 0.008 and 0.5 μg/ml for M. haemolytica (MIC90 = 0.139 μg/ml; MIC50 = 0.021 μg/ml), between 0.004 and 0.5 μg/ml for P. multocida (MIC90 = 0.028 μg/ml; MIC50 = 0.012 μg/ml). In 2008, the marbofloxacin MIC50 for E. coli isolated from bovine mastitis was 0.021 μg/ ml and the MIC90 was 0.038 μg/ml. Strains with MIC ≤ 1 μg/ml are sensitive to marbofloxacin whereas strains with MIC ≥ 4 μg/ml are resistant to marbofloxacin. Resistance to fluoroquinolones occurs by chromosomal mutation with three mechanisms: decrease of the bacterial wall permeability, expression of efflux pump or mutation of enzymes responsible for molecule binding. 5.2 Pharmacokinetic particulars: After a single intramuscular administration in cattle at the recommended dose of 10 mg/kg body weight, the maximum plasma concentration of marbofloxacin (Cmax) is 7.915 μg/ml reached in 1.28 h (Tmax) for an exposure (AUCINF) of 52.7 μg.h/mL. Bioavailability after intramuscular injection is complete (more than 90%). Marbofloxacin is extensively distributed. Binding to plasma proteins is about 30%. After intravenous or intramuscular administration, marbofloxacin concentrations in milk increase rapidly and the AUCINF , Tmax and Cmax values obtained in plasma and milk after both administration routes are similar. Marbofloxacin is eliminated slowly (T1/2lz = 17.50 h) predominantly as the active form in urine and faeces. 6. PHARMACEUTICAL PARTICULARS: 6.1. List of excipients: Benzyl alcohol, Glucono-delta-lactone, Water for injection. 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: Details of the primary packaging: Amber type II glass vials. Chlorobutyl rubber stopper. Aluminium cap or flip cap. Pack sizes: Cardboard box containing one 50 ml vial. Cardboard box containing one 100 ml vial. Cardboard box containing one 250 ml vial. 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: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. United Kingdom. 8. MARKETING AUTHORISATION NUMBER(S): UK: Vm 08007/4130. IE: 10966/037/001. 9. DATE OF FIRST AUTHORISATION: UK: 25 July 2011. IE: 22 July 2011. 10. DATE OF REVISION OF THE TEXT: July 2012 . PROHIBITION OF SALE, SUPPLY AND/OR USE. To be supplied only on veterinary prescription. Administration by a veterinary surgeon or under their direct responsibility. *IV route.