Sulfacetamide Sodium and Prednisolone Sodium Phosphate

INDICATIONS AND USAGE Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution is indicated for corticosteroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. Ocular corticosteroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe where the inherent risk of corticosteroid use in certain infective conjunctivitides is accepted to obtain 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 superficial ocular 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 drug in this product is active against the following common bacterial eye pathogens: Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus (viridans group), Haemophilus influenzae, Klebsiella species, and Enterobacter species. This product does not provide adequate coverage against: Neisseria species, Serratia marcescens . A significant percentage of staphylococcal isolates are completely resistant to sulfa drugs.

DOSAGE AND ADMINISTRATION Instill two drops of Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution topically in the eye(s) every four hours. Not more than 20 mL should be prescribed initially. If signs and symptoms fail to improve after two days, patients should be re-evaluated (see PRECAUTIONS ). Care should be taken not to discontinue therapy prematurely. In chronic conditions, withdrawal of treatment should be carried out by gradually decreasing the frequency of application. FOR OPHTHALMIC USE ONLY

WARNINGS NOT FOR INJECTION INTO THE EYE. Prolonged use of corticosteroids may result in ocular hypertension/glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Acute anterior uveitis may occur in susceptible individuals, primarily Blacks. Prolonged use of Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution 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 topical corticosteroids. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection. If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Corticosteroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently. The use of corticosteroids after cataract surgery may delay healing and increase the incidence of filtering blebs. The use of ocular corticosteroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of corticosteroid medication in the treatment of herpes simplex requires great caution. A significant percentage of staphylococcal isolates are completely resistant to sulfonamides. Topical corticosteroids are not effective in mustard gas keratitis and Sjögren's keratoconjunctivitis. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this preparation. Cross-sensitivity among corticosteroids have been demonstrated (see ADVERSE REACTIONS ). Do not administer this product to patients who are sensitive/allergic to thimerosal or any other mercury containing ingredient.

CONTRAINDICATIONS Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. This product is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation, to other sulfonamides, or to other corticosteroids. (Hypersensitivity to the antimicrobial components occurs at a higher rate than for other components).

Drug Interactions Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution is incompatible with silver preparations. Local anesthetics related to p-aminobenzoic acid may antagonize the action of the sulfonamides.

ADVERSE REACTIONS Adverse reactions have occurred with corticosteroid/anti-infective combination drugs which can be attributed to the corticosteroid 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 ingredient are allergic sensitizations. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias (see WARNINGS ). Sulfacetamide sodium may cause local irritation. The reactions due to the corticosteroid 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 occurrences of systemic hypercorticoidism after use of topical corticosteroids. Corticosteroid-containing preparations can also cause acute anterior uveitis or perforation of the globe. Mydriasis, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids. Secondary Infection The development of secondary infection has occurred after use of combinations containing corticosteroids and antimicrobials. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of corticosteroid. The possibility of fungal invasion must be considered in any persistent corneal ulceration where corticosteroid treatment has been used. Secondary bacterial ocular infection following suppression of host responses also occurs. To report SUSPECTED ADVERSE REACTIONS, contact Bausch + Lomb, a division of Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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. 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, plus assured compatibility of ingredients when both types of drugs are in the same formulation and, particularly, that the correct amount of drug is delivered and retained. The relative potency of a corticosteroid depends on the molecular structure, concentration, and release from the vehicle. Microbiology Sulfacetamide sodium exerts a bacteriostatic effect against susceptible bacteria by restricting the synthesis of folic acid required for growth through competition with p-aminobenzoic acid. Some strains of bacteria may be resistant to sulfacetamide or resistant strains may emerge in vivo . The anti-infective component in Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution is included to provide action against specific organisms susceptible to it. Sulfacetamide sodium is active in vitro against susceptible strains of the following microorganisms: Escherichia coli, Staphylococcus aureus, Streptococcus (viridans group) , Haemophilus influenzae, Klebsiella species and Enterobacter species. The product does not provide adequate coverage against: Neisseria species, Pseudomonas species, Serratia marcescens (see INDICATIONS AND USAGE ).