Off yellow, opalescent, viscous suspension. Each ml contains Marbofloxacin 3mg, Clotrimazole 10mg and Dexamethasone acetate 1mg (equivalent to Dexamethasone 0.9 mg) as active substances. And Propyl gallate (E310) 1mg as an excipient.

Other excipients: Triglycerides medium-chain, Sorbitan oleate & Silica,hydrophobic colloidal

Treatment of otitis externa of both bacterial and fungal origin respectively due to bacteria sensitive to marbofloxacin, and fungi especially Malassezia pachydermatis sensitive to clotrimazole. Dexamethasone acetate for anti-inflammatory and anti-pruritic activity. The product should be used based on susceptibility testing.

FOR AURICULAR USE ONLY

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

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

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

Shake well for 30 seconds before use and squeeze gently to fill the dropper with the product.

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

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.

Do not use in dogs suffering from perforation of the tympanic membrane. Before treating with the product, the integrity of the tympanic membrane must be verified.

Do not use in cases of hypersensitivity to the active substances, to other azole antifungal agents or to any other fluoroquinolones or to any of the excipients.

Do not use in animals, where resistance of causative agents to marbofloxacin and/or clotrimazole is known.

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

Before treating with the product, the integrity of the tympanic membrane must be verified. Use of the product should be based on susceptibility testing of the bacteria and/or fungi isolated from the animal. If this is not possible, therapy should be based on local (regional) epidemiological information about susceptibility of the target pathogens.

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

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.

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.

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

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

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

Wash hands carefully after applying the product.

Avoid contact with eyes. If splashed in the eye, rinse with large amounts of clean water.

If skin or eye symptoms persist, or the product is accidentally swallowed, seek medical attention and show the package insert to the physician.

People with known hypersensitivity (allergy) to (fluoro)quinolones, (cortico)steroids or antifungals and to other ingredients in the product should take care to avoid contact with the product during administration.

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

Do not store above 30 °C.

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

Shelf-life of unopened packaging: 24 months.

Shelf life of opened packaging: 3 months.

Boxes containing: 10 ml LDPE bottle and dropper and 20 ml LDPE bottle with 2 droppers.

KRKA, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

Pharmacotherapeutic group: Otologicals, corticosteroids and anti-infectives in combination, dexamethasone and anti-infectives.

ATCvet code: QS02CA06

Marbofloxacin, 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 (Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis). In the European literature susceptibility data (MIC50 values) for canine and feline otitis pathogens are presented:

Microorganism MIC50 (µg/ml)

Ps. aeruginosa 0.5

S. (pseudo)intermedius 0.25

S. aureus 0.25

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. 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, 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.

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, predominantly in urine (2/3) and in faeces (1/3). Clotrimazole absorption is extremely poor (plasma concentration < 0.04 µg/ml).

Dexamethasone acetate plasma concentration reaches 1.25 ng/ml on the 14th day of treatment. Dexamethasone resorption is not increased by the inflammatory process induced by otitis.

Vm 01656/4117