Ear drops/cutaneous suspension. White suspension.

Active substances:

Miconazole nitrate 23.00 mg (equivalent to 19.98 mg miconazole)

Prednisolone acetate 5.00 mg

Polymyxin B sulfate 5500 IU (equivalent to 0.5293 mg polymyxin B sulfate)

Dogs and cats.

For the treatment of primary and secondary infections of skin (eczema, dermatitis, pyoderma) and skin adnexa (hair, claws, sweat glands), as well as for the treatment of otitis externa, caused by infections with the following miconazole and polymyxin B sensitive pathogens:

Gram-positive bacteria Staphylococcus spp. Streptococcus spp.

Gram-negative bacteria Pseudomonas spp. Escherichia coli Yeasts and fungi Malassezia pachydermatis Candida spp.

Microsporum spp.

Trichophyton spp.

For the topical treatment of otitis externa caused by the ear mite Otodectes cynotis.

This product is for topical administration.

Shake the bottle vigorously and ensure the product is fully resuspended before use.

At the beginning of treatment, hair surrounding or covering the lesions must be clipped; this should be repeated during treatment if necessary.

Ears: Clean the auditory canal and place a few drops of the product into the ear twice daily.

For infections caused by Otodectes cynotis, instill five drops twice daily for 14 days. Massage the ear and the auditory canal gently but thoroughly to ensure proper distribution.

Skin: Having ensured the area to be treated is clean, apply a few drops of the product (depending on lesion size) twice a day and rub well. Treatment should be continued until a few days after complete disappearance of the clinical symptoms. In some obstinate cases, treatment may be required for 2 to 3 weeks (see also Adverse Reactions).

Where ear mite infestation is present, consideration should be given to treating both ears even if infestation is only apparent in one ear.

Corticosteroids are not recommended for use in pregnant animals.

Do not use in animals with perforated ear drums since Polymyxin B is known to be a potential ototoxic agent. Do not use in cases of hypersensitivity to the active substances or to any of the excipients.

Dog, cat:

Deafness1

Local immune deficiency2,3

Skin thinning2

Delayed healing2

Teleangiectasia2

Increased vulnerability of the skin (with bleeding)2

1 In animals treated for otitis externa, especially in older dogs. Treatment should be discontinued.

2 With prolonged use due to the contained glucocorticoid.

3 Associated with increased susceptibility to infection.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or the national competent authority via the national reporting system. See also section 16 of the package leaflet for contact details.

Corticosteroids are not recommended for use in pregnant animals.

Do not use concomitantly with medicines that induce ototoxicity.

In case of overdose, no other adverse events are known other than those mentioned in section 4.6. In case of accidental ingestion by licking, no toxic effects were observed.

Special precautions for use in animals For external use only. Due to the likely variability (temporal, geographical) in the emergence of bacterial resistance to polymyxin B, bacteriological sampling and sensitivity testing (antibiogram) is recommended. If there is overgrowth of resistance bacteria and/or fungi, treatment with this product should be discontinued and treatment with an appropriate alternative should be initiated.

People with known hypersensitivity to prednisolone, polymyxin B or miconazole should avoid contact with the veterinary medicinal product. The veterinary medicinal product may cause irritation to skin and eyes. Avoid contact with skin or eyes. Personal protective equipment consisting of single use disposable gloves should be worn when applying the veterinary medicinal product to animals. In case of accidental spillage, skin or eyes should be rinsed immediately with plenty of water. Take care to avoid accidental ingestion, especially by a child. In case of accidental ingestion, seek medical advice immediately and show the leaflet or the label to the physician. Wash hands after use.

Not applicable.

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

6 months

Store below 25 °C. Store in the original container in order to protect from light.

Medicines should not be disposed of via wastewater. Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

Folding box consist of: - white bottle 15 ml, made of low density polyethylene (LDPE) - white dropper, made of low density polyethylene (LDPE) - white screw closure with tamper proof ring, made of high density polyethylene (HDPE)

KRKA, d.d., Novo mesto

Smarjeska cesta 6 8501

Novo mesto

Slovenia

Silica, colloidal anhydrous Paraffin, liquid

Otologicals, Corticosteriods and antiinfectives in combination

QS02CA01

Polymyxin B - Polymyxin B belongs to the polypeptide antibiotics which are isolated from bacteria. It is only active against Gram-negative bacteria, such as Pseudomonas spp., Enterobacter, E. coli, Salmonella spp., and Shigella spp. The mechanism of action is damage of the microbial cytoplasmic membrane, because polypeptides act as cationic detergents. This results bactericidal effect. Resistance of Gram-negative bacteria to polymyxin may result from chromosomal mutations or horizontal transfer of the MCR gene. All Proteus species have a natural resistance to polymyxin.

Miconazole - Miconazole belongs to the group of N-substituted imidazole derivatives. Their most important mechanism of action is the inhibition of ergosterol biosynthesis. Ergosterol is an essential membrane lipid and must be synthesised de novo by fungi. The lack of ergosterol impedes numerous membrane functions and ultimately leads to cell death. The spectrum of activities covers nearly all fungi and yeasts of relevance to veterinary medicine as well as Gram-positive bacteria. Practically no development of resistance has been reported. Miconazole has a fungistatic mode of action, but high concentrations are also observed to produce fungicidal effects.

Prednisolone - Prednisolone is a synthetic corticosteroid and is used for its anti-inflammatory, antipruritic, anti- exudative and anti-proliferative effects. This quickly leads to a symptomatic relief in inflammatory skin diseases.

Its anti-inflammatory activity is approx. 4 - 5 times more potent than that of natural cortisol. Like other glucocorticoids, prednisolone binds to intracellular cytoplasmic receptors in the target organs. After the translocation of the receptor complex into the nucleus it causes derepression of the DNA and subsequently an increase in mRNA synthesis and ultimately protein synthesis. This increases the number of catabolic enzymes for gluconeogenesis. Inhibitory proteins, such as the phospholipase A2-inhibiting lipocortin, are formed. Consequently, the typical glucocorticoid effects and the associated effects are observed. Effects are noticeable only after a latency period. They persist beyond the elimination of the glucocorticoid from the bloodstream as long as there are receptor-glucocorticoid complexes in the nucleus present.

Polymyxin B - After topical application of polymyxin B, there is virtually no absorption of the ingredient through intact skin and mucous membranes, but significant absorption via wounds.

Miconazole - After topical application of miconazole, there is virtually no absorption of the ingredient through intact skin or mucous membranes.

Prednisolone - After topical application of prednisolone to intact skin, the ingredient is subject to limited and delayed absorption. Greater proportion of the applied ingredient can be absorbed in cases of compromised skin barrier function (e.g. skin lesions).

Vm 01656/5072