Remicin

Gentamicin Sulfate USP, Betamethasone Valerate, USP and Clotrimazole, USP Ointment
Veterinary
For Otic Use in Dogs Only
Anada #200-229, Approved by FDA
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 gentamicin-betamethasone-clotrimazole ointment contains gentamicin sulfate USP equivalent to 3 mg gentamicin base; betamethasone valerate, USP equivalent to 1 mg betamethasone and 10 mg clotrimazole, USP in a mineral oil-based system contained a plasticized hydrocarbon gel.

Pharmacology:

Gentamicin: Gentamicin sulfate is an aminoglycoside antibiotic active against a wide variety of pathogenic gram-negative and gram-positive bacteria. In vitro tests have determined that gentamicin is bactericidal and acts by inhibiting normal protein synthesis is susceptible microorganisms. Specifically, gentamicin is active against the following organisms commonly isolated from canine ears: Staphylococcus aureus, other Staphylococcus spp., Pseudomonas aeruginosa, Proteus spp. And Escherichia coli.

Betamethasone: Betamethasone valerate is a synthetic adrenocorticoid for dermatologic use. Betamethasone, an analog of prednisolone, has a high degree of corticosteroid activity and a slight degree of mineralocosteroid activity. Betamethasone valerate, the 17-valerate ester or betamethasone, has been shown to provide anti-inflammatory and antipruritic activity in the topical management or corticosteroid-responsive otitis externa. 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 anti-fungal angent that is used for the treatment of dermal infectionals caused by various species of pathogenic dermatophytes and yeasts. 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, 1% clotrimazole in gentamicin-betamethasone-clotrimazole ointment vehicle was effective both microbiologically and clinically in terms of reduction of exudates odor or swelling.

In studies of the mechanism in action, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phorphorus 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.

Gentrimacin-Betamethasone-Clotrimazole:
By virtue of its three active ingredients, gentamicin-betamethasone-clotrimazole ointment has antibacterial, anti-inflammatory and antifungal activity.

In component of efficacy studies, the compatibility and additive effect of each of the components were demonstrated. In clinical field trials, gentamicin-betamethasone-clotrimazole was effective in the treatment of otitis externa associated with bacteria and Malassezia pachydermatis. Gentamicin sulfate USP, Betamethasone valerate, USP and Clotrimazole USP ointment reduced discomfort, redness, swelling, exudates and odor and exerted a strong antimicrobial effect.

Indications: Gentamicin-betamethasone-clotrimazole ointment is indicated for the treatment of canine acute and chronic otitis externa associated with yeast (Malassezia pachydermatis, formerly Pityrosporum canis) and/or bacteria susceptible to gentamicin.

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 gentamicin-betamethasone-clotrimazole ointment has been associated with deafness or partial hearing loss in a small number of sensitive dogs (e.g. geriatric). The hearing deficit is usually temporary. If hearing or vestibular dysfunction is noted during the course of treatment, discontinue use of gentamicin-betamethasone-clotrimazole ointment immediately and flush the ear canal thoroughly with a non-ototoxic solution. Corticosteroids administered to dogs, rabbits and rodents during pregnancy have resulted in cleft palate in offspring. Other congenital anomalies including deformed forelegs, phocornelia and anasarca have been reported in offspring of dogs which received corticosteroids during pregnancy.

Clinical and experimental data have demonstrated that corticosteroids 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.

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

Precautions:
Identification of infecting organisms should be made either by microscopic roll smear evaluation or by culture as appropriate. Antibiotic susceptibility of the pathogenic organism(s) should be determined prior to use of this preparation.

If overgrown or nonsusceptible bacteria, fungi or yeasts occur, or if hypersensitivity develops, treatment should be discontinued and appropriate therapy instituted.

Administration of recommended doses of gentamicin-betamethasone-clotrimazole ointment beyond seven days may result in delayed wound-healing.

Avoid ingestion. Adverse systemic reactions have been observed following oral ingestions of some topical corticosteroid preparations. Patients should be closely observed for the usual sighs 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 the 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 situation.

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

Toxicology:
Clinical and safety studies with Gentamicin sulfate USP, Betamethasone valerate, USP and Clotrimazole USP ointment has been shown a wide safety margin as recommended dose level in dogs (see Precautions/Side Effects).

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

Betamethasone: Side effects such as SAP and SGPT enzyme elevations, weight loss, anorexia, polydipsia and polyuria have occurred following the use of parenteral or systemic synthetic corticosteroids in dogs. Vomiting and diarrhea (occasionally bloody) have been observed in dogs and cats. Cushing’s syndrome in dogs have been reported in association with prolonged or repeated steroid therapy.

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

Dosage and Administration:
The external ear should be thoroughly cleaned and dried before treatment. Remove foreign material, debris, crusted exudates, etc., with suitable nonirritating solutions. Excessive hair should be clipped from the treatment area. After verifying that the eardrum is intact, instill 4 drops (2 drops from the 214 g. bottle) of gentamicin-betamethasone-clotrimazole ointment twice daily into the ear canal of dogs weighing 30 lbs. or more. Therapy should continue for 7 consecutive days.

How Supplied: Gentamicin-betamethasone-clotrimazole ointment is available in 7.5 gram and 15 gram tubes as well as in 10 gram, 15 gram, 25 gram and 215 gram plastic bottles.

Store between 2° and 25°C (36°F and 77°F). Shake well before use when using the 215 gram bottle.

January 2001

MED-PHARMEX, Inc.
Pomona, CA 91767