SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Marbodex Aural Ear Drops, Suspension for Dogs (UK, IE, MT)

Marbodex Ear Drops, Suspension for Dogs (AT, BE, BG, CY, CZ, DE, EE, EL, ES, FR, HR, HU, IT, LT, LU, LV, NL, PL, PT, RO, SI, SK)

Norotic vet Ear Drops, Suspension for Dogs (DK, FI, NO, SE)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml contains:

Active substances:

Marbofloxacin 3.0 mg

Clotrimazole 10.0 mg

Dexamethasone 0.9 mg

(equivalent to dexamethasone acetate 1.0 mg)

Excipients

Propyl gallate (E310)……………………………………… 1.0 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Ear drops, suspension

Homogenous beige to yellow oily suspension

4. CLINICAL PARTICULARS

4.1. Target species

Dogs

4.2. Indications for use, specifying the target species

Treatment of otitis externa of both bacterialandfungal origin respectively due to bacteria sensitive to marbofloxacin, and fungi especially Malassezia pachydermatissensitive to clotrimazole.

The product should be used based on susceptibility testingof isolated bacteria.

Do not use in dogs suffering from perforation of the tympanic membrane.

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

See section 4.7.

4.4. Special warnings for each target species

The external ear canal should be meticulously cleaned and dried before treatment.

Bacterial and fungal otitis is often secondary in nature. The underlying cause should be identified and treated.

4.5. Special precautions for use

Special precautions for use in animals

For external use only. Auricular use.

Avoid contact with eyes in animals. In case of accidental contact, rinse thoroughly with water.

Heavy reliance on a single class of antibiotic may result in the induction of resistance in a bacterial population. It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions which have responded poorly, or are expected to respond poorly, to other classes of antibiotics.

Before treating with the product, the integrity of the tympanic membrane must be verified.

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

See section 4.4

Quinolone class drugs have been associated with cartilage erosions in weight-bearing joints and other forms of arthropathy in immature animals of various species. The use of the product in young animals is not recommended.

Special precautions to be taken by the person administering the medicinal products to animals

Wash hands carefully after applying the product.

Avoid contact with eyes. In the event of accidental eye contact, rinse with clean water.

People with known hypersensitivity to fluoro(quinolones) and other compounds in the product should avoid contact with the veterinary medicinal product.

4.6. Adverse reactions (frequency and seriousness)

Usual adverse reactions associated with corticosteroid drugs may be observed (changes in biochemical and haematological parameters, such as increase of alkaline phosphatase, and of aminotransferase, some limited neutrophilia).

Prolonged and intensive use of topical corticosteroid preparations is known to trigger local and systemic effects, including suppression of adrenal function, thinning of the epidermis and delayed wound healing.

On rare occasions, the use of this product may be associated with deafness, mainly in elderly dogs and mostly of a transient nature.

4.7. Use during pregnancy, lactation

Do not administer to pregnant or lactating bitches.

4.8. Interaction with other medicinal products and other forms of interaction

None known

Auricular use.

One drop of the preparation contains 71µg marbofloxacin, 237µg clotrimazole and 23.7µg dexamethasone acetate.

Shake well for 1 minute before use.

Apply ten drops into the ear once daily for 7 to 14 days.

After application, the base of the ear may be massaged briefly and gently to allow the preparation to penetrate to the lower part of the ear canal.

After 7 days of treatment, the veterinary surgeon should evaluate the necessity to extend the treatment an other week.

When the product is intended for use in several dogs, use one cannula per dog.

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

Changes in biochemical and haematological parameters (such as increase of alkaline phosphatase, aminotransferase, some limited neutrophilia, eosinopenia, lymphopenia) are observed with three fold the recommended dosage; such changes are not serious and will reverse once the treatment has stopped.

4.11. Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: corticosteroids and antiinfectives in combination

ATC vet code: QS02CA06

The preparation combines three active ingredients:

Marbofloxacin is a synthetic bactericidal agent belonging to the fluoroquinolone family that acts by inhibiting DNA gyrase. It exhibits a broad spectrum of activity against Gram-positive bacteria (e.g. Staphylococcus intermedius) and against Gram-negative organisms (Pseudomonasaeruginosa, Escherichia coliand Proteus mirabilis).

For Marbofloxacin:

European literature reports of microbiological susceptibility data (collected from 1994 – 2012) involving hundreds of canine and feline pathogens susceptible to marbofloxacin are outlined.

Microorganism	MIC (µg/ml)
Staph pseudintermedius	0.125-1
Pseudomonas	0.12-1

Susceptibility breakpoints have been determined as ≤ 1 µg/ml for sensitive, 2 µg/ml for intermediate and ≥ 4 µg/ml for resistant bacterial strains.

Marbofloxacin is not active against anaerobes, yeast or fungi. 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.

Clotrimazole is an anti-fungal agent that belongs to the imidazole family and which acts by causing changes in membrane permeability, allowing intracellular compounds to leak from the cell and thus inhibiting cellular molecular synthesis. It exhibits a wide spectrum of activity and is aimed, in particular, at Malassezia pachydermatis.

For Clotrimazole:

Susceptibility breakpoints have been determined as ≤ 25 µg/ml for sensitive fungal strains.

Dexamethasone acetate is a synthetic glucocorticoid exhibiting anti-inflammatory and anti-pruritic activity.

Pharmacokinetics studies in dogs at the therapeutic dosage have shown that: Marbofloxacin plasma concentrations peak at 0.06 µg/ml on the 14th day of treatment. Marbofloxacin bonds weakly to plasma proteins (< 10% in dogs) and is eliminated slowly, mainly in the active form, over 2/3 in urine and over 1/3 in faeces. Clotrimazole absorption is extremely poor (plasma concentration < 0.04 µg/ml). Dexamethasone acetate plasma concentration reaches 1.25 ng/ml on the 14^thday of treatment. Dexamethasone resorption is not increased by the inflammatory process induced by otitis.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Propyl gallate (E310)

Sorbitan oleate

Silica, hydrophobic colloidal

Triglycerides, medium-chain

6.2. Incompatibilities

Not applicable

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: 3 months.

Do not store above 30°C.

6.5. Nature and composition of immediate packaging

Details of the primary packaging:

Low-density polyethylene bottle.

Low-density polyethylene nozzle.

Threaded high-density polyethylene cap.

PVC cannula.

Presentation :

-Box containing 1 x 10 ml bottle and 2 cannulae

-Box containing 1 x 20 ml bottle and 2 cannulae

-Box containing 1 x 30 ml bottle and 2 cannulae

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

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

Norbrook Laboratories Limited

Station Works

Camlough Road

Newry

Co. Down

BT35 6JP

Northern Ireland

8. MARKETING AUTHORISATION NUMBER

Vm 02000/4392

9. DATE OF FIRST AUTHORISATION

24 August 2015

10. DATE OF REVISION OF THE TEXT

August 2015

Approved: 24/08/2015