SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Marbox 100 mg/ml solution for injection for cattle and pigs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substance:

Marbofloxacin 100.0 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear yellow solution.

4. CLINICAL PARTICULARS

4.1 Target species

Cattle and pigs (sows).

4.2 Indications for use, specifying the target species

Cattle:

Therapeutic treatment of respiratory infections caused by sensitive strains of Pasteurella multocida, Mannheimia haemolyticaand Histophilus somni.

Therapeutic treatment of acute mastitis caused by E. colistrains sensitive to marbofloxacin during the lactation period.

Sows:

Treatment of Metritis Mastitis Agalactia Syndrome caused by bacterial strains sensitive to marbofloxacin.

4.3 Contraindications

Do not use in case of known hypersensitivity to the active substance or other (fluoro)quinolones or to any of the excipients.

Do not use in case of confirmed or suspected resistance to fluoroquinolones (cross resistance).

4.4 Special warnings

None.

4.5 Special precautions for use

Special precautions for use in animals

Use of the product should be based on susceptibility testing and has to take into account official and local antimicrobial policies.

It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions that have responded poorly, or are expected to respond poorly, to other classes of antibiotics.

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.

As the vial cannot be broached more than 45 times, the user should choose the most appropriate vial size according to the target species to treat.

For the injections, the neck should be preferred in cattle and pigs.

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.

Take care to avoid accidental self-injection since it can induce a slight irritation.

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

Wash hands after use.

4.6 Adverse reactions (frequency and seriousness)

Administration by the intramuscular route may cause in cattle transient local reactions such as pain at the injection site and slight muscular inflammatory lesions (resulting in fibrosis). The process of cicatrisation starts rapidly (varying from fibrosis to synthesis of extracellular matrice and collagen) and may persist for at least 15 days after injection.

Administration by the subcutaneous route may induce slight to moderate oedema at the injection site. A moderate pain on palpation of the injection site occurred in some animals.

In pigs, administration by the intramuscular route may induce very transient slight oedema and mild inflammatory lesions at the injection site persisting for 12 days after injection.

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 2 mg/kg has been shown in cows during gestation and in suckling pigs and calves when used in sows and cows.

Safety of the product at 8 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

Cattle:

Intramuscular use:

- Respiratory infections:

The recommended dosage is 8 mg/kg bodyweight i.e. 2 ml/25 kg bodyweight in a single injection.

If the volume to be injected is more than 20 ml, it should be divided between two or more injection sites.

Subcutaneous use:

- Acute mastitis:

The recommended dosage is 2 mg/kg i.e. 1 ml/50 kg bodyweight in a single daily injection, for 3 days.

The first injection may also be given by the intravenous route too.

Sows:

Intramuscular use:

The recommended dosage is 2 mg/kg i.e.1 ml/50kg bodyweight in a single daily injection by intramuscular route, for 3 days.

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

No sign of overdosage has been observed in cattle after administration of 3 times the recommended dose.

Overdosage may cause signs such as acute neurological disorders which should be treated symptomatically.

4.11 Withdrawal period(s)

Cattle:

Intramuscular: Meat and offal: 3 days - Milk : 72 hours

Subcutaneous: Meat and offal: 6 days - Milk: 36 hours

Sows:

Intramuscular: Meat and offal: 4 days

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: anti-infectives for systemic use, fluoroquinolones class

ATCvet code: QJ01MA93

5.1 Pharmacodynamic properties

Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group, which acts by inhibition of DNA gyrase. It has a broad-spectrum activity in vitroagainst Gram-negative bacteria (Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, E. coli) and against Gram-positive bacteria (in particular Staphylococcus).

Resistance to Streptococcusmay occur.

Strains with MIC ≤ 1 µg/ml are sensitive to marbofloxacin whereas strains with MIC > 2 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.

Cattle- Intramuscular route

After a single intramuscular administration at the recommended dose of 8 mg/kg, the maximum plasma concentration of marbofloxacin (Cmax) is 8 µg/ml reached in approximatively 1 hour (Tmax). Marbofloxacin is eliminated slowly (terminal T1/2 = 9.5 h), predominantly in the active form in urine and faeces.

Cattle- Subcutaneous route

After subcutaneous administration at the recommended dose of 2 mg/kg, marbofloxacin is readily absorbed and reaches maximal plasma concentrations of 1.7 µg/ml in approximately 1 hour. The terminal elimination half-life (t_½) of marbofloxacin is 5.6 hours.

Pigs- Intramuscular route

After intramuscular administration at the recommended dose of 2 mg/kg, marbofloxacin is readily absorbed and reaches maximal plasma concentrations of 1.7 µg/ml in approximately 1 hour. The terminal elimination half-life (t_½) of marbofloxacin is 8.7 hours.

Its bioavailability is close to 100 %.

Marbofloxacin is weakly bound to plasma proteins (less than 10% in pigs and 30 % in cattle), extensively distributed and in most tissues (liver, kidney, skin, lung, bladder, uterus) it achieves higher concentrations than in plasma.

Marbofloxacin is eliminated predominantly in the active form in urine and faeces.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glucono-delta-lactone.

Water for injections.

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

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

6.5 Nature and composition of immediate packaging

Primary packaging:

Amber PP/Ethylene vinyl alcohol/PP multi-layer plastic vials.

Type II chlorobutyl rubber stopper

Aluminium and plastic flip capsule.

Pack size

Cardboard box containing one 50 ml vial

Cardboard box containing one 100 ml vial

Cardboard box containing one 250 ml vial

Cardboard box containing one 500 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 product should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Ceva Animal Health Ltd

Unit 3, Anglo Office Park

White Lion Road

Amersham

Buckinghamshire

HP7 9FB

8. MARKETING AUTHORISATION NUMBER

Vm 15052/4048

9. DATE OF FIRST AUTHORISATION

10 November 2010

10. DATE OF REVISION OF THE TEXT

October 2015

Approved: 08 October 2015