Osurnia (Canada)

Company: Dechra

Florfenicol, Terbinafine, and Betamethasone Acetate Gel

For Veterinary Use Only

For Use in Dogs Only

DIN 02438534

Description

Osurnia otic gel contains 10 mg of florfenicol, 10 mg of terbinafine and 1 mg of betamethasone acetate per mL in an off-white to slightly yellow translucent gel. Each tube contains not less than 2.0 g of gel with a deliverable volume of 1.0 mL (1.2 g).

Therapeutic Classification

Antibacterial, antifungal and anti-inflammatory.

Osurnia Indications

Osurnia is indicated for the treatment of otitis externa in dogs associated with bacteria (Staphylococcus pseudintermedius) susceptible to florfenicol and/or fungi (Malassezia pachydermatis) susceptible to terbinafine, and for the reduction of clinical signs commonly associated with this condition.

Osurnia Dosage And Administration

Treatment with Osurnia requires two doses seven (7) days apart and should be administered in clinic by a veterinary professional. Wear eye protection when administering Osurnia (see WARNINGS). Splatter may occur if the dog shakes its head following administration. Persons near the dog during administration should also take steps to avoid ocular exposure.

Clean the external ear canal with saline and dry before administering the initial dose of the product. Verify that the tympanic membrane is intact prior to each administration. Administer one dose (one tube) per affected ear and repeat administration 7 days later.

The maximal clinical response may be seen from 30-45 days after the first administration. Do not clean the ear canal for 45 days after initiation of treatment (cleaning the ear may affect product effectiveness). If alternative otic therapies are required, it is recommended to clean the ear(s) before administration.

Open the tube by twisting the soft tip. Introduce this flexible soft tip into the ear canal. Dispense the entire tube contents into the ear canal by pressing it between two fingers. After application, the base of the ear should be massaged briefly and gently to facilitate even distribution of the drug formulation in the ear canal.

Restrain dog to minimize post application head shaking to reduce potential for splatter of product and accidental eye exposure in people and dogs.

Appropriate diagnosis should be used and therapy of causative conditions should be investigated before antimicrobial treatment is considered.

Whenever possible the use of the veterinary medicinal product should be based on identification of infecting organisms and susceptibility testing.

Contraindications

Do not use in case of hypersensitivity to the active ingredients, to other corticosteroids or to any of the excipients.

Do not use in dogs with generalized demodicosis.

Do not use if the eardrum is perforated.

Osurnia Cautions

Do not administer orally.

Avoid accidental contact with the dog’s eyes during administration of Osurnia by restraining the dog to minimize head shaking. In case of exposure to the eye, flush thoroughly with water for 10 to 15 minutes and seek medical advice.

The use of Osurnia in dogs with perforated tympanic membranes has not been evaluated. The integrity of the tympanic membrane should be confirmed before administering each dose of this product. Re-evaluate the dog if hearing loss or signs of vestibular dysfunction are observed during treatment.

Changes to the middle ear such as ulceration of the mucosal lining have been associated with Osurnia administration. Signs of tympanic membrane rupture, internal ear disease such as head tilt, ataxia, nystagmus, facial paralysis, and keratoconjunctivitis sicca have also been reported (see ADVERSE REACTIONS).

Use of topical otic corticosteroids has been associated with adrenocortical suppression and iatrogenic hyperadrenocorticism in dogs (see SAFETY AND EFFICACY STUDY INFORMATION).

Use with caution in dogs with impaired hepatic function.

Use with caution in dogs affected with suspected or confirmed endocrine disorder. Metabolic clearance of corticosteroids is decreased in hypothyroidism and increased in hyperthyroidism. Glucocorticoids can decrease total thyroxine levels (T3 and T4). Therefore, thyroid function test results should be interpreted carefully in any dog receiving glucocorticoids.

The safe use of Osurnia has not been established in dogs less than 2 months of age or weighing less than 1.4 kg, in dogs used for breeding purposes, or in pregnant or lactating bitches.

Warnings

Not for use in humans. Keep out of reach of children.

Consult a physician in case of accidental ingestion by humans and show the leaflet or the label to the physician. In case of accidental skin contact, wash exposed skin thoroughly with water. Wear eye protection when administering Osurnia and restrain the dog to minimize post application head shaking. Reducing the potential for splatter of product will help prevent accidental eye exposure in people. Osurnia may cause eye injury and irritation. Avoid accidental contact with the eyes. Accidental exposure leading to corneal ulcers and other ocular injuries such as eye irritation, burning, stinging, and itchiness have been reported to occur in humans when the dog shook its head after application of Osurnia. If accidental ocular exposure does occur, flush eyes thoroughly with water for 10 to 15 minutes and seek medical advice.

Adverse Reactions

Although not all adverse reactions are reported, the following information is based on voluntary post-approval drug experience reporting. It is generally recognized that this results in significant under-reporting. The adverse events listed here reflect reporting and not necessarily causality. The adverse events reported with Osurnia in dogs are presented below in decreasing order of reporting frequency:

Systemic disorders: lack of efficacy*, anorexia, lethargy.

Ear and labyrinth disorders: deafness, internal ear disorder (head tilt, vestibular disorders), ear discharge, tympanic rupture.

Neurological disorders: ataxia, nystagmus, cranial nerve disorder (facial paralysis).

Eye disorders: keratoconjunctivitis sicca, corneal ulcer, blepharospasm/squinting.

Application site disorders: application site redness, application site pain, application site itching.

*While post-approval reports of lack of efficacy have been received for this product, the frequency of such reports remains in line with the expected efficacy (see SAFETY AND EFFICACY STUDY INFORMATION). It is important to note that efficacy of the product may be affected if the underlying causes of the condition such as allergy or anatomical conformation of the ear are not addressed in animals with a history of chronic or recurrent otitis externa. Perceived lack of efficacy may result from extra-label use. This product choice should be based on identification of the infecting organism(s) and susceptibility testing (see DOSAGE AND ADMINISTRATION).

Osurnia is not approved for use in cats. The adverse events reported following extra-label use in cats are presented below in decreasing order of frequency:

Ataxia, Horner’s syndrome (third eyelid prolapse and miosis), internal ear disorder (head tilt and vestibular), anisocoria, lethargy, head shake, emesis, nystagmus, deafness, and tympanic rupture.

Information For Dog Owners

Owners should be aware that adverse reactions may occur following administration of Osurnia and should observe dog for signs such as deafness, ear pain and irritation, vomiting, head shaking, head tilt, incoordination, eye pain and ocular discharge (see ADVERSES REACTIONS). Owners should be advised to contact their veterinarian if any of the above signs are observed. Owners should also be informed that splatter may occur if the dog shakes its head following administration of Osurnia which may lead to ocular exposure. As a result, eye injuries in humans and dogs have been reported including corneal ulcers. Owners should be careful to avoid ocular exposure (see CAUTIONS and WARNINGS).

Clinical Pharmacology

Osurnia is a fixed combination of three active ingredients: florfenicol (antibacterial), terbinafine (antifungal) and betamethasone acetate (steroidal anti-inflammatory). Florfenicol is a bacteriostatic antibiotic which acts by inhibiting protein synthesis. Its spectrum of activity includes Gram-positive and Gram-negative bacteria. Terbinafine is an allylamine with a pronounced fungicidal activity. It selectively inhibits the early synthesis of ergosterol, which is an essential component of the membrane of yeasts and fungi including Malassezia pachydermatis. Terbinafine has a different mode of action than azole antifungals, therefore there is no cross resistance with azole antifungals. Betamethasone acetate belongs to the esters class of the glucocorticosteroids with a potent intrinsic glucocorticoid activity which decreases both inflammation and pruritus leading to an improvement of clinical signs observed in otitis externa.

Following auricular application, the extent of percutaneous absorption of topical medications is determined by many factors including the integrity of the epidermal barrier. When an ear infection is present, ear inflammation can increase the percutaneous absorption of the active ingredients in Osurnia. Osurnia dissolves in ear wax and is slowly eliminated from the ear mechanically.

In a margin-of-safety study conducted in healthy mixed breed hound dogs (n=8/group) where Osurnia was aurally administered at 0X, 1X (1 mL/ear or 2 mL/dog with repeated administration in 7 days), 5X (5 mL/ear or 10 mL/dog with repeated administration in 7 days) doses for a total of 6 administrations in 5 weeks, low plasma concentrations of florfenicol, terbinafine, and betamethasone were detectable during the first 2-4 days after administration of 1X dose, and during the first 2-7 days after administration of 5X dose. No quantifiable plasma concentrations of terbinafine and betamethasone were observed in 1X and 5X dogs in the pre-dose samples prior to second and third administrations. Some treated dogs had detectable plasma concentrations of florfenicol.

A toxicokinetic study conducted in six healthy mongrel dogs, where 3 dogs were treated with Osurnia at the recommended 1X dose (1 mL/ear or 2 mL/dog with repeated administration in 7 days) and 3 dogs were treated at the 5X dose (5 mL/ear or 10 mL/dog with repeated administration in 7 days), showed that for all three active ingredients, there was a dose-proportional increase in plasma levels without systemic accumulation between the two 7-day-apart administrations.

Microbiology

The compatibility and additive effect of each of the components in Osurnia otic gel was demonstrated in a component effectiveness and non-interference study. An in vitro study of organisms collected from clinical cases of otitis externa in dogs determined that florfenicol and terbinafine inhibit the growth of bacteria and yeast commonly associated with otitis externa in dogs. No consistent synergistic or antagonistic effect of the two antimicrobials was demonstrated. The addition of betamethasone acetate to the combination did not impair antimicrobial activity to any clinically significant extent.

Safety And Efficacy Study Information

In a target animal safety study, 24 mixed breed hound dogs (4 dogs/sex/group) were aurally administered 0X, 1X (1 mL/ear or 2 mL/dog with repeated administration in 7 days) or 5X (5 mL/ear or 10 mL/dog with repeated administration in 7 days) doses of Osurnia for a total of 6 administrations in 5 weeks. All dogs remained in good health with normal hearing throughout the study. Decreased weight gain was noted in the 1X and 5X groups compared to the control group. Clinical findings included post-administration ear wetness in 1X and 5X groups and unilateral, transient brown/red discharge in two 5X dogs, with erythema in one of these dogs, after the 4th application. Local microscopic changes in ears (without clinical effects) included: slight or moderate unilateral vesicle formation within the epithelium of the tympanic membrane in two 1X and four 5X dogs; and unilateral mucosal ulceration in the lining of the middle ear cavity in three 5X dogs. Three 5X dogs had slightly elevated ALT activity, accompanied by minimal or mild microscopic hepatocellular vacuolation (in two dogs). Cortisol response to ACTH stimulation was decreased, but within the normal reference range, in 1X dogs. The 5X dogs had a decrease in serum cortisol levels after ACTH stimulation (below normal reference range) accompanied by decreased adrenal gland and thymic weights with minimal adrenal cortical atrophy and slight (in three dogs) or moderate (in one dog also noted with slightly lower lymphocyte counts) lymphoid depletion of the thymus. These changes were not associated with clinical signs of hypoadrenocorticism in 5X dogs. The ACTH stimulation test results are consistent with systemic absorption of betamethasone resulting in a likely reversible suppression of the hypothalamic-pituitary-adrenal axis as seen with administration of exogenous corticosteroids.

In an acute eye irritation study, Osurnia was demonstrated to be moderately irritating with corneal involvement or positive conjunctival irritation clearing in 7 days or less.

In a clinical safety study, 190 dogs receiving Osurnia were evaluated for clinical safety: 15 (7.9%) dogs treated with Osurnia had mild elevations in ALP outside the normal reference range compared to three (3.2%) dogs treated with placebo with no associated physical exam findings. Seven dogs (3.7%) were reported to have vomiting compared to one dog of 94 (1.1%) treated with the placebo control. In addition, two dogs (1.1%) with pre-existing elevations in ALP and treated with Osurnia were reported to have an increase in liver enzymes (ALP, ALT and/or AST) at study exit. Subsequent clinical chemistries returned to pre-treatment levels in one dog, while no follow up was performed for the second dog. One dog with chronic bilateral otitis externa had a transient decrease in hearing during treatment with Osurnia and fully recovered while remaining on study. A placebo control dog was reported with loss of hearing and was withdrawn from the study on Day 14. One dog treated with Osurnia and diagnosed with chronic, severe otitis externa and a history of mass removal was withdrawn from the study and at exit on Day 14 had a 13% body weight loss.

Effectiveness was evaluated in 240 dogs. The study was a double- blinded study with a placebo control (vehicle without the active ingredients). One hundred and sixty-two (162) dogs were treated with Osurnia otic gel and seventy-eight (78) dogs were treated with the placebo control. All dogs were evaluated for safety. Treatment (1 mL) was administered to the affected ear(s) and repeated 7 days later. Prior to the first administration, the ear(s) were cleaned with saline but not prior to the Day 7 administration. Six clinical signs associated with otitis externa were evaluated: pain, erythema, exudate, swelling, odor and ulceration. Total clinical scores were assigned for a dog based on the severity of each clinical sign on Days 0, 7, 14, 30 and 45. Success was determined by clinical improvement at Day 45. The success rates of the two groups were significantly different (p=0.0073); 65.4% of dogs administered Osurnia otic gel were successfully treated, compared to 43.6% of the dogs in the placebo control group. There was a marked improvement of all types of otitis externa following treatment with Osurnia compared to those treated with the placebo control, with a higher success rate for acute otitis (85%) compared to subchronic (65.6%) and chronic (52.5%) otitis.

Storage

Osurnia should be stored under refrigerated conditions between 2°C and 8°C. To facilitate comfort during administration, Osurnia may be brought to room temperature and stored for up to three months. Discard after three months storage at room temperature.

Osurnia should at no time be used beyond its expiration date after storage at both refrigerated and room temperature.

Dechra Ltd., Snaygill Industrial Estate, Keighley Road, North Yorkshire, United Kingdom, BD23 2RW

Imported and Distributed by:

Dechra Veterinary Products Inc., 1 Holiday Ave, East Tower, Suite 345, Pointe-Claire, Quebec, H9R 5N3, Canada

PIL-44027-002

Presentation: 2 and 20 packs.

CPN: 1786062.1