DuOtic Dailymed

Antifungal, anti-inflammatory

For Otic Use in Dogs OnlyDo not use in cats

Caution:

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Description:

DuOticâ„¢ contains 10 mg terbinafine and 1 mg betamethasone acetate per mL and the inactive ingredients propylene carbonate, glycerol formal, hypromellose, phospholipid, oleic acid and butylated hydroxytoluene in an off-white to slightly yellow translucent gel.

Indication:

DuOticâ„¢ is indicated for the treatment of otitis externa in dogs, associated with susceptible strains of yeast (Malassezia pachydermatis).

Dosage And Administration:

DuOticâ„¢ should be administered by a veterinary professional. Wear eye protection when administering DuOticâ„¢ (see Human Safety Warnings, Precautions, Post-approval Experience, and Target Animal Safety ).

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 and dry the external ear canal before administering the initial dose of the product.
• Verify the tympanic membrane is intact prior to each administration (see Precautions, Contraindications, Target Animal Safety and Post-approval Experience ).
• Administer one dose (1 tube) per affected ear. Repeat administration in 7 days.
• Open tube by twisting the soft tip. Insert the flexible tip in the affected external ear canal and squeeze entire tube contents into the external ear canal. After application, gently massage the base of the ear to allow the gel to penetrate the lower part of 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 (see Post-Approval Experience and Target Animal Safety ).
• Do not clean the ear canal for 45 days after the initial administration to allow contact of the gel with the ear canal. Cleaning the ear may affect product effectiveness (see Effectiveness ). If alternative otic therapies are required, it is recommended to clean the ear(s) before application of those therapies.

Contraindications:

Do not use in dogs with known tympanic perforation (see Precautions ). Do not use in dogs with a hypersensitivity to terbinafine or corticosteroids.

Warnings:

Human Safety Warnings:

DuOticâ„¢ may cause eye injury and irritation (see Precautions, Post-approval Experience and Target Animal Safety ).

In case of accidental eye contact, flush thoroughly with water for at least 15 minutes. If wearing contact lenses, rinse eyes first then remove contact lenses and continue to rinse. If symptoms develop, seek medical advice.

Not for use in humans. Keep this and all medications out of reach of children. Consult a physician in case of accidental ingestion by humans. In case of accidental skin contact, wash area thoroughly with water.

Precautions:

Wear eye protection when administering DuOticâ„¢ 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 and dogs and help to prevent eye injury (see Human Safety Warnings, Post-approval Experience and Target Animal Safety ). Avoid hand-to-eye contact.

Proper patient selection is important when considering the benefits and risks of using DuOticâ„¢. The use of DuOticâ„¢ 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. Reevaluate 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 administration of Osurnia^® (florfenicol, terbinafine, betamethasone acetate). The presentation and concentrations of terbinafine and betamethasone acetate in DuOtic™ are identical to the concentrations of these active ingredients in Osurnia^® (see Target Animal Safety ).

Signs of tympanic membrane rupture, internal ear disease such as head tilt, ataxia, nystagmus, facial paralysis, and keratoconjunctivitis sicca have also been reported in relation to the administration of Osurnia^® (see Post-approval Experience ).

Do not administer orally.

Use of topical otic corticosteroids has been associated with adrenocortical suppression and iatrogenic hyperadrenocorticism in dogs (see Target Animal Safety ).

Use with caution in dogs with impaired hepatic function (see Target Animal Safety and Adverse Reactions ).

The safe use of DuOticâ„¢ has not been evaluated in dogs that are pregnant, lactating or intended for breeding.

Adverse Reactions:

The following adverse reactions were reported during the course of a US field study for treatment of otitis externa in dogs treated with DuOticâ„¢ with 1 tube per affected ear(s) and repeated after 7 days:

Number (%) of dogs with Adverse Reactions by Treatment

Adverse Reaction	DuOticâ„¢(n=120)	Control(n=119)
Elevated alanine aminotransferaseFour dogs were reported to have an increase in alanine aminotransferase at Study Exit. The levels reported in subsequent clinical chemistries returned to normal in three dogs, while no follow up was performed for the fourth dog.	4 (3.3%)	0 (0.0%)
Conjunctivitis	1 (0.8%)	0 (0.0%)
Ocular discharge	1 (0.8%)	2 (1.7%)
Ear discharge	0 (0.0%)	1 (0.8%)
Ear pruritus	3 (2.5%)	4 (3.4%)

Post-Approval Experience:

The following adverse events are based on post-approval adverse drug experience reporting for Osurnia^® (florfenicol, terbinafine, betamethasone acetate). The presentation and concentrations of terbinafine and betamethasone acetate in DuOtic™ are identical to the concentrations of these active ingredients in Osurnia^®. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data.

In humans, accidental exposure leading to corneal ulcers and other ocular injuries such as eye irritation, burning, stinging, and itchiness have been reported to occur when the dog shook its head after application of Osurnia^®.

In dogs, the adverse events reported for Osurnia^® are presented below in decreasing order of reporting frequency:

Deafness, ear discharge, pinnal irritation and ear pain, emesis, head shaking, internal ear disorder (head tilt and vestibular), ataxia, vocalization, corneal ulcer, keratoconjunctivitis sicca, nystagmus, tympanic rupture, and cranial nerve disorder (facial paralysis).

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 reporting frequency:

Ataxia, anorexia, 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.

Contact Information:

To report suspected adverse drug events and/or to obtain a copy of the Safety Data Sheet (SDS) or for technical assistance, contact Dechra at 1-866-933-2472.

For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae.

Information For Dog Owners:

Owners should be aware that adverse reactions may occur following administration of DuOticâ„¢ and should observe their dog for signs such as deafness, ear pain and irritation, vomiting, head shaking, head tilt, incoordination, eye pain and ocular discharge (see Animal Safety and Post-approval Experience ). 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 DuOtic™ which may lead to eye exposure. As a result, eye injuries in humans and dogs have been reported including corneal ulcers following the use of a similar product (Osurnia^®). Owners should be careful to avoid ocular exposure (see Precautions and Post-approval Experience ).

Clinical Pharmacology:

DuOticâ„¢ is a fixed combination of two active ingredients: terbinafine (antifungal) and betamethasone acetate (steroidal anti-inflammatory). Terbinafine is an antifungal which selectively inhibits the early synthesis of ergosterol. Betamethasone acetate is a glucocorticosteroid with anti-inflammatory activity.

DuOticâ„¢ dissolves in ear wax and is slowly eliminated from the ear mechanically. Ear inflammation can increase the percutaneous absorption of active substances in DuOticâ„¢.

In a laboratory study conducted in healthy dogs administered Osurnia^® (see Target Animal Safety ), low plasma concentrations of florfenicol, terbinafine, and betamethasone acetate were measurable 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 any of the three active ingredients were observed in the pre-dose samples of most dogs prior to second and third administrations. Although total and peak exposure in the blood tended to be highly variable between dogs, systemic drug concentrations tended to increase in a less than dose-proportional manner as the administered dose increased from 1X to 5X. The systemic exposure of terbinafine and betamethasone are not expected to be affected by the removal of florfenicol from the formulation.

Mycology:

The compatibility of the components of DuOticâ„¢ was demonstrated in a non-interference study. An in vitro study of organisms collected from clinical cases of otitis externa in dogs determined that terbinafine inhibits the growth of Malassezia pachydermatis, a yeast commonly associated with otitis externa in dogs. The presence of betamethasone acetate in the formulation did not impair the antifungal effect of terbinafine to any clinically significant extent. In a field study (see Effectiveness ), the minimum of 10 isolates from successfully treated cases with DuOticâ„¢ was met for Malassezia pachydermatis.