Prescription Drugs

CLINICAL PHARMACOLOGY Corticosteroids suppress the inflammatory response to a variety of agents and they probably delay or slow healing. Since corticosteroids may inhibit the body's defense mechanism against infection, a concomitant antimicrobial drug may be used when this inhibition is considered to be clinically significant in a particular case. The anti-infective components in POLY-PRED® (prednisolone,neomycin and polymyxin b) ophthalmic suspension are included to provide action against specific organisms susceptible to them. Neomycin sulfate and polymyxin B sulfate are considered active against the following microorganisms: Staphylococcus aureus; Escherichia coli; Hemophilus influenzae; Klebsiella/ Enterobacter species; Neisseria species; and Pseudomonas aeruginosa. When a decision to administer both a corticosteroid and an antimicrobial is made, the administration of such drugs in combination has the advantage of greater patient compliance and convenience, with the added assurance that the appropriate dosage of both drugs is administered. When both types of drugs are in the same formulation, compatibility of ingredients is assured and the correct volume of drug is delivered and retained. The relative potency of corticosteroids depends on the molecular structure, concentration and release from the vehicle.

POLY-PRED® (prednisolone acetate, neomycin sulfate, polymyxin B sulfate) Ophthalmic Suspension, USP Sterile DESCRIPTION POLY-PRED® (prednisolone acetate, neomycin sulfate, polymyxin B sulfate ophthalmic suspension, USP) is a topical anti-inflammatory/anti-infective combination product for ophthalmic use with a pH of 5.0 - 7.0 and an osmolality of 260-340 mOsm/kg. Structural Formulas: Chemical Name: Prednisolone acetate: 11β, 17, 21-Trihydroxypregna-1, 4-diene-3, 20-dione 21-acetate. Neomycin sulfate is the sulfate salt of neomycin B and neomycin C which are produced by the growth of Streptomyces fradiae (Fam. Streptomycetaceae). It has a potency equivalent to not less than 600 micrograms per milligram of neomycin base, calculated on an anhydrous basis. Polymyxin B sulfate is the sulfate salt of polymyxin B1 and polymyxin B2 which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillaceae). It has a potency of not less than 6,000 polymyxin B units per milligram, calculated on an anhydrous basis. Contains: Actives: prednisolone acetate (microfine suspension) 0.5%, neomycin sulfate equivalent to 0.35% neomycin base, polymyxin B sulfate 10,000 units/mL. Inactives: polysorbate 80; polyvinyl alcohol; propylene glycol; purified water; sodium acetate; and thimerosal 0.001% (preservative). The pH range is 5.0 - 7.0.

INDICATIONS A steroid/anti-infective combination is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial ocular infection exists. Ocular steroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in edema and inflammation. They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation, or thermal burns or penetration of foreign bodies. The use of a combination drug with an anti-infective component is indicated where the risk of infection is high or where there is an expectation that potentially dangerous numbers of bacteria will be present in the eye. The particular anti-infective drugs in this product are active against the following common bacterial eye pathogens: Staphylococcus aureus; Escherichia coli; Hemophilus influenzae; Klebsiella/ Enterobacter species; Neisseria species; and Pseudomonas aeruginosa. The product does not provide adequate coverage against: Serratia marcescens; Streptococci, including Streptococcus pneumoniae. DOSAGE AND ADMINISTRATION TO TREAT THE EYE: Instill 1 or 2 drops every 3 or 4 hours, or more frequently as required. Acute infections may require administration every 30 minutes, with frequency of administration reduced as the infection is brought under control. TO TREAT THE LIDS: Instill 1 or 2 drops in the eye every 3 to 4 hours, close the eye and rub the excess on the lids and lid margins. Not more than 20 milliliters should be prescribed initially and the prescription should not be refilled without further evaluation as outlined in the PRECAUTIONS section above. HOW SUPPLIED POLY-PRED® (prednisolone,neomycin and polymyxin b) (prednisolone acetate, neomycin sulfate, polymyxin B sulfate ophthalmic suspension, USP) is supplied sterile in opaque white LDPE plastic bottles with droppers with white high impact polystyrene (HIPS) caps as follows: 5 mL in 10 mL bottle – NDC 0023-0028-05 Note: Store at 15 - 25°C (59 - 77°F). Protect from freezing. Shake well before using. Store in an upright position. Revised: 05/2006. Allergan, Inc. Irvine, CA 92612, U.S.A.

PATIENT INFORMATION If inflammation or pain persists longer than 48 hours or becomes aggravated, the patient should be advised to discontinue use of the medication and consult a physician (See WARNINGS). This product is sterile when packaged. To prevent contamination, care should be taken to avoid touching the applicator tip to eyelids or to any other surface. The use of this bottle by more than one person may spread infection. Keep bottle tightly closed when not in use. Keep out of the reach of children. Patients should be advised not to wear contact lenses if they have signs and symptoms of ocular bacterial infections.

OVERDOSE No information provided. CONTRAINDICATIONS Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and many other viral diseases of the cornea and conjunctiva. Mycobacterial infection of the eye. Fungal diseases of the ocular structures. Hypersensitivity to a component of the medication. (Hypersensitivity to the antibiotic component occurs at a higher rate than for other components.) The use of these combinations is always contraindicated after uncomplicated removal of a corneal foreign body.

SIDE EFFECTS Adverse reactions have occurred with steroid/anti-infective combination drugs which can be attributed to the steroid component, the anti-infective component, or the combination. Exact incidence figures are not available since no denominator of treated patients is available. Reactions occurring most often from the presence of the anti-infective ingredients are allergic sensitizations including itching, swelling, and conjunctival erythema (see WARNINGS). More serious hypersensitivity reactions, including anaphylaxis, have been reported rarely. The reactions due to the steroid component in decreasing order of frequency are: elevation of intraocular pressure (IOP) with possible development of glaucoma, and infrequent optic nerve damage; posterior subcapsular cataract formation; and delayed wound healing. Although systemic effects are extremely uncommon, there have been rare occurences of systemic hypercorticoidism after use of topical steroids. Corticosteroid-containing preparations have also been reported to cause perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, and conjunctival hyperemia have occasionally been reported following local use of steroids. Secondary infection: The development of secondary infection has occurred after use of combinations containing steroids and antimicrobials. Fungal infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion must be considered in any persistent corneal ulceration where steroid treatment has been used. Secondary bacterial ocular infection following suppression of host responses also occurs. DRUG INTERACTIONS No information provided.

WARNINGS NOT FOR INJECTION INTO THE EYE. Prolonged use may result in glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of Stopical steroids. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection. If these products are used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Employment of a steroid medication in the treatment of herpes simplex requires great caution. There exists a potential for neomycin sulfate to cause cutaneous sensitization. The exact incidence of this reaction is unknown. The manifestations of sensitization to topical antibiotics are usually itching, reddening, and edema of the conjunctiva and eyelid. A sensitization reaction may manifest simply as a failure to heal. During long-term use of topical antibiotic products, periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. Symptoms usually subside quickly on withdrawing the medication. Application of products containing these ingredients should be avoided for the patient thereafter (see PRECAUTIONS: General). PRECAUTIONS General The initial prescription and renewal of the medication order beyond 20 milliliters should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. The possibility of persistent fungal infections of the cornea should be considered after prolonged steroid dosing. As with other antimicrobial preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated. Bacterial resistance to POLY-PRED® (prednisolone,neomycin and polymyxin b) ophthalmic suspension may also develop. If purulent discharge, inflammation, or pain becomes aggravated, the patient should discontinue use of the medicatioin and consult a physician. Allergic cross-reactions may occur which could prevent the use of any or all of the following antibiotics for the treatment of future infections: kanamycin, paromomycin, streptomycin, and possibly gentamicin. Carcinogenesis, Mutagenesis, Impairment of Fertility: No studies have been conducted in animals or in humans to evaluate the potential of these effects due to prednisolone. Treatment of human lymphocytes in-vitro with neomycin increased the frequency of chromosome aberrations at the highest concentration (80 µg/mL) tested; however, the effects of neomycin on carcinogenesis and mutagenesis in humans are unknown. No studies have been conducted with polymyxin B sulfate to evaluate carcinogenic or mutagenic potential. Polymyxin B has been reported to impair the motility of equine sperm, but its effects on male or female fertility are unknown. Pregnany: Teratogenic Effects Pregnancy Category C Prednisolone has been shown to be teratogenic in rabbits, hamsters, and mice. In mice, prednisolone has been shown to be teratogenic when given in doses 1 to 10 times the human ocular dose. Dexamethasone, hydrocortisone and prednisolone were applied to both eyes of pregnant mice five times per day on days 10 through 13 of gestation. A significant increase in the incidence of cleft palate was observed in the fetuses of the treated mice. There are no adequate well-controlled studies in pregnant women dosed with corticosteroids. Animal reproduction studies have not been conducted with polymyxin B sulfate or neomycin sulfate. It is also not known whether polymyxin B sulfate or neomycin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. POLY-PRED® (prednisolone,neomycin and polymyxin b) ophthalmic suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers This drug is excreted in human milk. Caution should be exercised when POLY-PRED® (prednisolone,neomycin and polymyxin b) ophthalmic suspension is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.