Gentacort

Betamethasone Sodium Phosphate:

• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Gentacort (Betamethasone Sodium Phosphate) reviews

Gentacort (Betamethasone Sodium Phosphate) Spray is indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.

Gentacort (Betamethasone Sodium Phosphate) Spray is a corticosteroid indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older. (1)

2 DOSAGE AND ADMINISTRATION

Shake well before use.

Apply Gentacort (Betamethasone Sodium Phosphate) Spray to the affected skin areas twice daily and rub in gently.

Use Gentacort (Betamethasone Sodium Phosphate) Spray for up to 4 weeks of treatment. Treatment beyond 4 weeks is not recommended.

Discontinue Gentacort (Betamethasone Sodium Phosphate) Spray when control is achieved.

Do not use if atrophy is present at the treatment site.

Do not bandage, cover, or wrap the treated skin area unless directed by a physician.

Avoid use on the face, scalp, axilla, groin, or other intertriginous areas.

Gentacort (Betamethasone Sodium Phosphate) Spray is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

• Apply to the affected skin areas twice daily. Rub in gently. (2)
• Use Gentacort (Betamethasone Sodium Phosphate) Spray for up to 4 weeks and not beyond. (2)
• Discontinue treatment when control is achieved. (2)
• Do not use if atrophy is present at the treatment site. (2)
• Do not use with occlusive dressings unless directed by a physician. (2)
• Avoid use on the face, scalp, axilla, groin, or other intertriginous areas. (2)
• Not for oral, ophthalmic, or intravaginal use. (2)

3 DOSAGE FORMS AND STRENGTHS

Spray, 0.05% for topical use. Each gram of Gentacort (Betamethasone Sodium Phosphate) Spray contains 0.643 mg Gentacort (Betamethasone Sodium Phosphate) dipropionate USP (equivalent to 0.5 mg Gentacort (Betamethasone Sodium Phosphate)) in a slightly thickened, white to off-white oil-in-water emulsion.

Spray: 0.05% (equivalent to 0.5 mg betamethasone/g) (3)

4 CONTRAINDICATIONS

None.

• None. (4)

5 WARNINGS AND PRECAUTIONS

• Gentacort Spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1)
• Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1)
• Use of topical corticosteroids may require periodic evaluation for HPA axis suppression. (5.1)
• Modify use if HPA axis suppression develops. (5.1)
• High potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure and young age may predispose patients to HPA axis suppression. (5.1)
• Pediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. (5.1, 8.4)

5.1 Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression and Other Unwanted Systemic Glucocorticoid Effects

Gentacort (Betamethasone Sodium Phosphate) Spray can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age.

Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test.

In a study including 48 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, abnormal ACTH stimulation test results suggestive of adrenal suppression were identified in 5 out of 24 (20.8%) subjects after treatment with Gentacort (Betamethasone Sodium Phosphate) Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with Gentacort (Betamethasone Sodium Phosphate) Spray twice daily for 29 days .

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental systemic corticosteroids may be required.

Systemic effects of topical corticosteroids may also manifest as Cushing’s syndrome, hyperglycemia, and glucosuria. These events are rare and generally occur after prolonged exposure to larger than recommended doses, particularly with high-potency topical corticosteroids.

Minimize the unwanted risks from endocrine effects by mitigating the risk factors favoring increased systemic bioavailability and by using the product as recommended .

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios. Use of Gentacort (Betamethasone Sodium Phosphate) Spray is not recommended in pediatric patients .

5.2 Allergic Contact Dermatitis

Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Corroborate such an observation with appropriate diagnostic patch testing. If irritation develops, discontinue the topical corticosteroid and institute appropriate therapy.

6 ADVERSE REACTIONS

The most common adverse reactions are application site reactions, including pruritus, burning and/or stinging, pain, and atrophy. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Promius Pharma, LLC. at 1-888-966-8766 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In two randomized, multicenter, prospective vehicle-controlled clinical trials, subjects with moderate plaque psoriasis of the body applied Gentacort (Betamethasone Sodium Phosphate) Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied Gentacort (Betamethasone Sodium Phosphate) Spray and 180 subjects applied vehicle spray.

Adverse reactions that occurred in at least 1% of subjects treated with Gentacort (Betamethasone Sodium Phosphate) Spray for up to 28 days are presented in Table 1.

Less common adverse reactions (with occurrence lower than 1% but higher than 0.1%) in subjects treated with Gentacort (Betamethasone Sodium Phosphate) spray were application site reactions including telangiectasia, dermatitis, discoloration, folliculitis and skin rash, in addition to dysgeusia and hyperglycemia. These adverse reactions were not observed in subjects treated with vehicle.

6.2 Postmarketing Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Postmarketing reports for local adverse reactions to topical corticosteroids have also included striae, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Gentacort Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Gentacort (Betamethasone Sodium Phosphate) dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias, cephalocele, and cleft palate.

8.3 Nursing Mothers

Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Gentacort (Betamethasone Sodium Phosphate) Spray is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Gentacort Spray in patients younger than 18 years of age have not been studied; therefore use in pediatric patients is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at greater risk of systemic toxicity, including HPA axis suppression and adrenal insufficiency, when treated with topical drugs. [see Warnings and Precautions (5.1)]

Rare systemic effects such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids.

Local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients.

8.5 Geriatric Use

Clinical studies of Gentacort (Betamethasone Sodium Phosphate) Spray did not include sufficient numbers of subjects who were 65 years of age or older to determine whether they respond differently from younger subjects.

11 DESCRIPTION

Gentacort (Betamethasone Sodium Phosphate) Spray contains 0.0643% Gentacort (Betamethasone Sodium Phosphate) dipropionate (equivalent to 0.05% Gentacort (Betamethasone Sodium Phosphate)), a synthetic, fluorinated corticosteroid.

The chemical name for Gentacort (Betamethasone Sodium Phosphate) dipropionate is 9-fluoro-11(β), 17, 21-trihydroxy-16(β)-methylpregna-1,4-diene-3,20-dione-17,21-dipropionate. The empirical formula is C₂₈H₃₇FO₇ and the molecular weight is 504.6. The structural formula is shown below.

Each gram of Gentacort (Betamethasone Sodium Phosphate) Spray contains 0.643 mg of Gentacort (Betamethasone Sodium Phosphate) dipropionate USP (equivalent to 0.5 mg Gentacort (Betamethasone Sodium Phosphate)) in a slightly thickened, white to off-white, oil-in-water, non-sterile emulsion with the following inactive ingredients:, butylated hydroxytoluene, cetostearyl alcohol, hydroxyethyl cellulose, methylparaben, mineral oil, oleyl alcohol, polyoxyl 20 cetostearyl ether, propylparaben, purified water, and sorbitan monostearate. Gentacort (Betamethasone Sodium Phosphate) Spray is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing to patients.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Gentacort Spray in psoriasis is unknown.

12.2 Pharmacodynamics

Vasoconstrictor studies performed with Gentacort (Betamethasone Sodium Phosphate) Spray in healthy subjects indicate that it is in the mid-range of potency as compared with other topical corticosteroids; however, similar blanching scores do not necessarily imply therapeutic equivalence.

The potential for HPA axis suppression by Gentacort (Betamethasone Sodium Phosphate) Spray was evaluated in a study randomizing 52 adult subjects with moderate to severe plaque psoriasis. Gentacort (Betamethasone Sodium Phosphate) Spray was applied twice daily for 15 or 29 days, in subjects with psoriasis involving a mean of 29.0% and 26.5% body surface area at baseline across the 2 treatment duration arms, respectively. Forty-eight (48) subjects were evaluated for HPA axis suppression at the end of treatment. The proportion of subjects demonstrating HPA axis suppression was 20.8% (5 out of 24) in subjects treated with Gentacort (Betamethasone Sodium Phosphate) Spray for 15 days. No subjects (0 out of 24) treated with Gentacort (Betamethasone Sodium Phosphate) Spray for 29 days had HPA axis suppression. In this study HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30-minutes post-cosyntropin stimulation. In the 4 subjects with available follow-up values, all subjects had normal ACTH stimulation tests at follow-up.

12.3 Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids are absorbed through normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Plasma concentrations of Gentacort (Betamethasone Sodium Phosphate) dipropionate, betamethasone-17-propionate, and Gentacort (Betamethasone Sodium Phosphate) were measured at baseline, and before and after the last dose (1, 3, and 6 hours) in the HPA axis suppression trial in subjects with psoriasis [see Clinical Pharmacology (12.2)]. The majority of subjects had no measurable plasma concentration (<5.00 pg/mL) of Gentacort (Betamethasone Sodium Phosphate) dipropionate, while the metabolites, betamethasone-17-propionate and Gentacort (Betamethasone Sodium Phosphate), were detected in the majority of subjects (Table 2). There was high variability in the data but there was a trend toward higher systemic exposure at Day 15 and lower systemic exposure at Day 29.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Gentacort (Betamethasone Sodium Phosphate) dipropionate.

In a 90-day repeat-dose toxicity study in rats, topical administration of Gentacort (Betamethasone Sodium Phosphate) dipropionate spray formulation at dose concentrations of 0.05% and 0.1% (providing dose levels up to 0.5 mg/kg/day in males and 0.25 mg/kg/day in females) resulted in a toxicity profile consistent with long-term exposure to corticosteroids including reduced body weight gain, adrenal atrophy, and histological changes in bone marrow, thymus and spleen indicative of severe immune suppression. A no observable adverse effect level (NOAEL) could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk of carcinogenesis.

Gentacort (Betamethasone Sodium Phosphate) was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in vitro human lymphocyte chromosome aberration assay, and equivocal in the in vivo mouse bone marrow micronucleus assay.

Studies in rabbits, mice, and rats using intramuscular doses up to 1, 33, and 2 mg/kg, respectively, resulted in dose-related increases in fetal resorptions in rabbits and mice.

14 CLINICAL STUDIES

Two multi-center, randomized, double-blind, vehicle-controlled clinical trials were conducted in subjects aged 18 years and older with moderate plaque psoriasis. In both trials, randomized subjects applied Gentacort (Betamethasone Sodium Phosphate) Spray or vehicle spray to the affected areas twice daily for 28 days. Enrolled subjects had body surface area of involvement between 10% to 20%, and an Investigator Global Assessment (IGA) score of 3 (moderate).

Efficacy was assessed as the proportion of subjects who were considered a treatment success (defined as having an IGA score of 0 or 1 [clear or almost clear] and at least a 2-grade reduction from baseline). Table 3 presents the efficacy results at Day 15 and Day 29.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied/Storage

Gentacort Spray is a slightly thickened, white to off-white, non-sterile emulsion supplied in high density polyethylene bottles with a heat induction seal lined polypropylene cap. The drug is supplied in the following volumes:

• 60 mL (NDC 67857-808-17)
• 120 mL (NDC 67857-808-04)

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) .

Each unit is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing.

16.2 Handling/Instructions for the Pharmacist

• Remove the spray pump from the wrapper.
• Remove and discard the cap from the bottle.
• Keeping the bottle upright, insert the spray pump into the bottle and turn clockwise until it is closed tightly.
• Dispense the bottle with the spray pump inserted.
• Include the date dispensed in the space provided on the carton.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Inform patients of the following:

• Discontinue therapy when control is achieved, unless directed otherwise by the physician.
• Do not use for longer than 4 consecutive weeks.
• Avoid contact with the eyes.
• Avoid use of Gentacort (Betamethasone Sodium Phosphate) Spray on the face, scalp, underarms, groin or other intertriginous areas, unless directed by the physician.
• Do not occlude the treatment area with bandage or other covering, unless directed by the physician.
• Local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids.

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

Gentacort (Betamethasone Sodium Phosphate) is a trademark of Promius Pharma, LLC.

Issued: 02/2016

007465

140728

Instructions for Use

Gentacort (Betamethasone Sodium Phosphate) (ser-ne-vo)

(betamethasone dipropionate)

Spray, 0.05%

Important: Gentacort (Betamethasone Sodium Phosphate) Spray is for use on the skin only. Do not get Gentacort (Betamethasone Sodium Phosphate) Spray near or in your eyes, mouth, or vagina.

Read this “Instructions for Use” before you start using Gentacort (Betamethasone Sodium Phosphate) Spray and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

Parts of the Gentacort (Betamethasone Sodium Phosphate) Spray bottle.

Figure A

How to apply Gentacort (Betamethasone Sodium Phosphate) Spray:

Step 1: Shake the Gentacort (Betamethasone Sodium Phosphate) Spray bottle well. Remove the cap from the pump top.

Step 2: Hold the bottle in an upright position while pointing the opening of the pump top in the direction of the affected area. To spray, push down on the pump top. Apply Gentacort (Betamethasone Sodium Phosphate) Spray to the affected area as instructed by your doctor. (See Figure B )

Figure B

Step 3: Spray only enough Gentacort (Betamethasone Sodium Phosphate) Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Gentacort (Betamethasone Sodium Phosphate) Spray gently.

Figure C

Repeat Steps 2 and 3 to apply Gentacort (Betamethasone Sodium Phosphate) Spray to other affected areas as instructed by your doctor.

Step 4: After applying Gentacort (Betamethasone Sodium Phosphate) Spray, place the cap back onto the pump top. (See Figure D )

Figure D

How should I store Gentacort (Betamethasone Sodium Phosphate) Spray?

• Store Gentacort (Betamethasone Sodium Phosphate) Spray at room temperature between 68°F to 77°F (20°C to 25°C).
• Throw away (discard) any unused Gentacort (Betamethasone Sodium Phosphate) Spray after 28 days.

Keep Gentacort (Betamethasone Sodium Phosphate) Spray and all medicines out of the reach of children.

This “Instructions for Use” has been approved by the U.S. Food and Drug Administration.

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

Gentacort (Betamethasone Sodium Phosphate) is a trademark of Promius Pharma, LLC.

Issued: 02/2016

007528

140693

Gentamicin Sulfate:

• Gentacort (Gentamicin Sulfate) reviews

F-27078915

NADA #141-177, Approved by FDA.

PRODUCT

INFORMATION

VETERINARY

For Otic Use in Dogs Only

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

Keep this and all drugs out of the reach of children.

DESCRIPTION Each gram of Gentacort (Gentamicin Sulfate) Otic Suspension contains Gentacort (Gentamicin Sulfate) sulfate, USP equivalent to 3 mg Gentacort (Gentamicin Sulfate) base; mometasone furoate monohydrate equivalent to 1 mg mometasone; and 10 mg clotrimazole, USP in a mineral oilbased system containing a plasticized hydrocarbon gel.

PHARMACOLOGY

Gentacort (Gentamicin Sulfate): Gentacort (Gentamicin Sulfate) sulfate is an aminoglycoside antibiotic active against a wide variety of gram-negative and grampositive bacteria. In vitro tests have determined that Gentacort (Gentamicin Sulfate) is bactericidal and acts by inhibiting normal protein synthesis in susceptible microorganisms. In clinical trials, Gentacort (Gentamicin Sulfate) was shown to have a range of activity against the following organisms commonly isolated from infected canine ears:

Pseudomonas spp. (including P. aeruginosa), coagulasepositive staphylococci, Enterococcus faecalis, Proteus mirabilis and beta-hemolytic streptococci.

Mometasone: Mometasone furoate monohydrate is a synthetic adrenocorticoid characterized by a novel (2') furoate 17-ester having chlorine at the 9 and 21 positions, which have shown to possess high topical potency.

Systemic absorption of mometasone furoate ointment was found to be minimal (2%) over 1 week when applied topically to dogs with intact skin. In a 6-month dermal toxicity study using 0.1% mometasone ointment on healthy intact skin in dogs, systemic effects typical of corticosteroid therapy were noted.

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the integrity of the epidermal barrier. Topical corticosteroids can be absorbed from normal, intact skin. Inflammation can increase percutaneous absorption. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.

Clotrimazole: Clotrimazole is a broad-spectrum antifungal agent that is used for the treatment of dermal infections caused by various species of dermatophytes and yeast. The primary action of clotrimazole is against dividing and growing organisms.

In vitro, clotrimazole exhibits fungistatic and fungicidal activity against isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, Candida spp., and Malassezia pachydermatis. Resistance to clotrimazole is very rare among the fungi that cause superficial mycoses. In an induced otitis externa study using dogs infected with Malassezia pachydermatis, 1% clotrimazole in the vehicle formulation was effective both microbiologically and clinically in terms of reduction of exudate, odor, and swelling.

In studies of the mechanism of action, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorus compounds into the ambient medium with concomitant breakdown of cellular nucleic acids and accelerated potassium efflux. These events began rapidly and extensively after addition of the drug. Clotrimazole is very poorly absorbed following dermal application.

Gentamicin-Mometasone-Clotrimazole: By virtue of its three active ingredients, Gentacort (Gentamicin Sulfate) Otic Suspension has antibacterial, anti-inflammatory, and antifungal activity. In clinical field trials, Gentacort (Gentamicin Sulfate) Otic Suspension was effective in the treatment of otitis externa associated with bacteria and Malassezia pachydermatis. Gentacort (Gentamicin Sulfate) Otic Suspension reduced discomfort, redness, swelling, exudate, and odor.

INDICATIONS Gentacort (Gentamicin Sulfate) Otic Suspension is indicated for the treatment of otitis externa in dogs caused by susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Pseudomonas spp. [including P. aeruginosa], coagulasepositive staphylococci, Enterococcus faecalis, Proteus mirabilis, and beta-hemolytic streptococci).

CONTRAINDICATIONS If hypersensitivity to any of the components occurs, treatment should be discontinued and appropriate therapy instituted. Concomitant use of drugs known to induce ototoxicity should be avoided. Do not use in dogs with known perforation of eardrums.

WARNINGS The use of these components has been associated with deafness or partial hearing loss in a small number of sensitive dogs (eg, geriatric). The hearing deficit is usually temporary. If hearing or vestibular dysfunction is noted during the course of treatment, discontinue use of Gentacort (Gentamicin Sulfate) Otic Suspension immediately and flush the ear canal thoroughly with a nonototoxic solution.

Corticosteroids administered to dogs, rabbits, and rodents during pregnancy have resulted in cleft palate in offspring. Other congenital anomalies including deformed forelegs, phocomelia, and anasarca have been reported in offspring of dogs that received corticosteroids during pregnancy.

Field and experimental data have demonstrated that corticostroids administered orally or parenterally to animals may induce the first stage of parturition if used during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.

PRECAUTIONS Before instilling any medication into the ear, examine the external ear canal thoroughly to be certain the tympanic membrane is not ruptured in order to avoid the possibility of transmitting infection to the middle ear as well as damaging the cochlea or vestibular apparatus from prolonged contact.

Administration of recommended doses of Gentacort (Gentamicin Sulfate) Otic Suspension beyond 7 days may result in delayed wound healing. If overgrowth of nonsusceptible bacteria or fungi occurs, treatment should be discontinued and appropriate therapy instituted.

Avoid ingestion. Adverse systemic reactions have been observed following the oral ingestion of some topical corticosteroid preparations. Patients should be closely observed for the usual signs of adrenocorticoid overdosage which include sodium retention, potassium loss, fluid retention, weight gain, polydipsia, and/or polyuria. Prolonged use or overdosage may produce adverse immunosuppressive effects.

Use of corticosteroids, depending on dose, duration, and specific steroid, may result in endogenous steroid production inhibition following drug withdrawal. In patients presently receiving or recently withdrawn from corticosteroid treatments, therapy with a rapidly acting corticosteroid should be considered in especially stressful situations.

TOXICOLOGY Field and safety studies with Gentacort (Gentamicin Sulfate) Otic Suspension have shown a wide safety margin at the recommended dose level in dogs (see PRECAUTIONS/ADVERSE REACTIONS ).

ADVERSE REACTIONS

Gentacort (Gentamicin Sulfate): While aminoglycosides are absorbed poorly from skin, intoxication may occur when aminoglycosides are applied topically for prolonged periods of time to large wounds, burns, or any denuded skin, particularly if there is renal insufficiency. All aminoglycosides have the potential to produce reversible and irreversible vestibular, cochlear, and renal toxicity.

Mometasone: ALP (SAP) and ALT (SGPT) enzyme elevations, weight loss, anorexia, polydipsia, polyuria, neutrophilia, and lymphopenia have occurred following the use of parenteral, high-dose, and/or prolonged or systemic synthetic corticosteroids in dogs. Cushing's syndrome in dogs has been reported in association with prolonged or repeated steroid therapy.

Clotrimazole: The following have been reported occasionally in humans in connection with the use of clotrimazole: erythema, stinging, blistering, peeling, edema, pruritus, urticaria, and general irritation of the skin not present before therapy.

Gentacort (Gentamicin Sulfate) Otic Suspension: In field studies following once daily teatment with Gentacort (Gentamicin Sulfate) Otic Suspension, ataxia, proprioceptive deficits, and increased water consumption were observed in less than 1% of 164 dogs. In a field study following twice-daily treatment with Gentacort (Gentamicin Sulfate) Otic Suspension, inflammation of the pinna and diarrhea were observed in less than 1% of 141 dogs.

DOSAGE AND ADMINISTRATION

The external ear canal should be thoroughly cleaned and dried before treatment. Verify that the eardrum is intact. For dogs weighing less than 30 lbs, instill 4 drops from the 7.5 g, 15 g, and 30 g bottles (2 drops from the 215 g bottle) of Gentacort (Gentamicin Sulfate) Otic Suspension once daily into the ear canal. For dogs weighing 30 lbs or more, instill 8 drops from the 7.5 g, 15 g, and 30 g bottles (4 drops from the 215 g bottle) once daily into the ear canal. Therapy should continue for 7 consecutive days.

HOW SUPPLIED Gentacort (Gentamicin Sulfate) Otic Suspension is available in 7.5 g (NDC 14043-120-75), 15 g (NDC 14043-120-15), 30 g (NDC 14043-120-30), and 215 g (NDC 14043-120-21) plastic bottles.

Store between 2° and 25°C (36° and 77°F). Shake well before use.

U.S. Patent No. 6,127,353.

Distributed by

PATTERSON VETERINARY

137 Barnum Road, Devens, MA 01434

www.pattersonvet.com

Made in Canada.

9/15

85239791