(sulfacetamide sodium-prednisolone acetate ophthalmic suspension, USP) 10%10.2%
BLEPHAMIDE ophthalmic suspension is a topical antHnflammatory/anti-infective
combination product for ophthalmic use.
Sulfacetamlde sodium: N·sulfanilytacetamide monosodium salt monohydrate.
Prednisolone acetate: 11 B, 17, 21-1lihydroxypregna-1, 4-diene-3, 2O-dione at-acetate.
suUacetamide sodium 10%, prednisolone acetate (microfme suspension) 0.2%.
benzalkonium chloride (0.004%). lnactlves: edetate disodium; po/ysofbate 80; polyvinyl ak:ohol 1.4%; potassium phosphate, monobasic; purified water; sodium phosphate, dibasic; sodium Ihiosu”ate; hydrochloric acid andIor sodium hydroxide to adjust the pH (6.6 to 7.2).
Corticosteroids suppress the inflaITmalOry response to a variety 01 agents
and they probably delay Of slow healing. Since corticosteroids may inhibit the body’s delense mechanismagainst Inlection, a concomitant antibacterial dnJg may be used when this inhibftion is considered to beclinicalty signiflC8rlt in a particular case.
Wheo a decision to administer both a oorticosIeroid and an antibacterial Is made, the administration of suchdrugs In combination has the advantage of greater patient compliance and convenience, with the addedassurance that the appropriate dosage 01 both drugs is administered. When both types 01 drugs are In thesame formulation, compatibility of ingredients Is assured and the correct volume 01 drug is delivered andretained. The relative potency of cortk:osteroids depends on the mokK:ular structure, concentration andrelease from the vehicle.
Sulfacetamide sodium exerts a bacteriostatic effect against susceptible bacteria byrestricting the synthesis of tone acid required for growth through competition with p-aminobenzoic acid.Some strains 01 these bacteria may be reslstant tosuHacetamide or resistent strains may emerge in vivo.The anli-infective component in these products is included to provide action against specific organismssusceptible to lt. Sullacetamide sodium is active in vitro against susceptible strains of the following
microorganisms: ESCherichia coil, Staphylococcus eereus. Streptococcus pneumoniae, Streptococcus(viridans group), Haemophilus influenzae, Klebsiella species, and Enterobacter species. This product doesnot provide adequate coverage against: Neisseria species, Pseudomonas species, and Serratia
rnarcescene (see INDICATIONS AND USAGE).
INDICATIONS AND USAGE:
A sterofdIanlHnfectiYe””combinatlon is indicated for steroid-responsive
inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocularinfection or a risk of bacterial ocular infection exists.
Ocular corticosteroids are indicated in inHammatory conditions of the palpebral and bulbar conjunctiva,comea, and anterior segment of the globe where the inherent risk of OOfticosteroid use in certain infectiveconjunctivitides is accepted to obtain diminution in edema and ntlammation. They are also micated inchronic anterior uveitis and corneal injury from chemical, radiation or thennaJ bums or penetration 01 foreignbodies.
The use of a combination drug with an antHnfective component is indicated where the risk of superficialocular infection Is high or where there Is an expectation that potentially dangerous numbers of bacteria willbe present in the eye.
The particular antibacterial drug in this product is active against the loIklwing common bacterial eyepathogens: Escherichia coli, Staphylococcus aureus, streptcccccce pneumonlae, Streptococcus (viridansgroup), Haemophilus oncenaae. Klebsiella species, and Enterobacter species. This product does notprovide adequate coverage against: Neisseria species, Pseudomonas species, and Serratia marcescens.
A signiflC8nt percentage of staphylococcal isolates are completety resistant to sulta drugs.
BLEPHAMIDE ophthalmic suspension is contraindicated In most viral diseases 01
the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitls), vaccinia, andvaricella, and also In mycobacteriallnlection 01 the eye and fungal diseases 01 ocular structures.This product Is also contraindicated in individuals with known or suspected hypersensitivity to any of theingredients 01 this preparation, to other suUonamides and to other corticosteroids. See WARNINGS.
(Hypersensitivity to the antimicrobial component occurs at a higher rate than for other components.)
NOT FOR INJECTION INTO THE EYE.
Prolonged use of corticosteroids may result in ocular hypertensionlglauooma with damage to the opticnerve, defects in visual actJity and fiekts 01 vision, and in posterior subcapsular cataract formation.Acute anterior uveftls may occur in susceptible individuals, primarily BlacKs.Prolonged use 01 BLEPHAMIDE3 ophthalmic suspension may suppress the host response and thusincrease the hazard of secondary- OC\J1ar Infections.. In thOse diseases causing thiMing of the cornea Of
sclera. perforation has been known to occur with the use of topical corticostef’oid. In acute purulentconditions of the eye, corticosteroids may mask inlection or enhance existing infection.If the product is used for 10 days Of longer, intraoctJlar pressure should be routinety monitored even thoughit may be difficult in children and uncooperative patents. Corticosteroids should be used with caution in the
presence of glaucoma. Intraocular pressure should be checked frequentty.
A signiflC8nl pefCerltage of staphyk)coccaJ isolates are compIetety resistant to sulfonamides.
The use of steroids after cataract surgery may delay healing and increase the Incidence of filtering blabs.The use of ocular corticosteroids may prolong the course and may exacerbate the severity of many viralinlections of the eye (including herpes simplex). EmplOyment of corticosteroid medication in the treatment ofherpes slmplex requires great caution.Topical steroids are not effective in mustard gas keratitis and S~ren’s keratoconjunctivitis.Fatalities have occurred, although rarely, due to severe reactions to sulfonamides includingstevere-Jchnscn syndrome, toxic epidermal necrcrssrs, fulminant hepatic necrosis, agranulocy1osls,aplastic anemla and other blood dyscrasias. Sensitization may recur when a sutlonamide is read ministered,irrespective 01 the route 01 administration.If signs 01 hypersensitivity or other serious reactions occur, discontinue use 01 this preparation.
Cross-sensitivity among corticosterolds has been demonstrated (see ADVERSE REACTIONS).
General: The initial prescription and renewal of the medication oroer beyond 20 millilitersof the suspension Should be made by a physician only after examination of the patient with the aid ofmagniflCStion. such as slit tamp biomicroscopy and, where appropriate, fluorescein staining. H signs andsymptoms laillO improve after two days, the patient Should be r&-eValuated.The possibility of fungal infections of the cornea should be considered after proionged corticosteroid dosing.Use with caution in patients with severe dry eye. Fungal cultures should be taken when appropriate.
The p-aminobenzoic acid present in purulent exudates competes with sulfonamides and can reduce theireffectiveness.
Information for Patients:
If inHammation or pain persists longer than 48 hours or becomes aggravated, thepatient should be advised to disoonlinue use of the med”1Cation and consuh a physician (see WARNINGS).Contact lenses should not be worn during the use of this product.This product Is sterile when packaged. To prevent contamination, care should be taken to avoid touchingthe applicator lip to eyelids or to any other surface. The use 01 this botne by more than one person mayspread infection. Keep bottle tightly closed when not in use. Protect from light. Sulfonamide solutions
darken on prolonged standing and exposure to heat and light. Do not use if solution has darkened.Yellowing does not affect activity. Keep out of the reach of children.
Eyelid cultures and tests to determine the susceptibility of organisms tosulfacetamide
may be indicated if signs and symptoms persist or recur in spite of the recommended course of treatmentwith BLEPHAMIDE~ ophthalmic suspension.
BlEPHAMIDE ophthalmic suspension is incompabble with silver preparations. Local
anesthetics related to p-aminobenzoic acid may antagonize the action of the sulfonamides.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Prednisolone has been reported to benoncarcinogenic. Long-term animal studies for carcinogenic potential have not been performed withsulfacetamide.
One author detected chromosomal nondisjunction in the yeast Saccharomyces cerevetae followingapplication of sulfacetamide sodium. The signilicance 01 this linding to topical ophthalmic use ofsulfacetamide sodium in the human is unknown.
Mutagenic studies with prednisolone have been negative. Studies on reproduction and fertility have notbeen performed with sulfacetamide. A long-term chronic toxicity study in dogs showed that high oral dosesof prednisolone prevented estrus. A decrease in fertility was seen in male and lemale rats thal were matedloIlowing oral dosing with another glucocorticosteroid.
Teratogenic Effects: Pregnancy Category C. Animal reproduction studies have not beenconducted with sulfacetamide sodium. 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 thehuman ocular dose. Dexamethasone, hydrocortisone and prednisolone were ocularty applied to both eyes
of pregnant mice five times per day on days 10 through 13 of gestation. A significant increase in theincidence of cleft palate was observed in the fetuses of the treated mice. There are no adequateweu-controuec studies in pregnant women dosed with corncoeterclds.Kernicterus may be precipitated in infants by sullonamides being given systemically during the thirdtrimester of pregnancy. It is not known whether sulfacetamide sodium can cause fetal harm whenadministered to a pregnant woman or whether it can affect reproductive capacity.
BlEPHAMIDE/8 ophthalmic suspension should be used during pregnancy only if the potential benefitjustifies the potential risk to the fetus.
It is not known whether topical administration of corticosteroids could result in sufficientsystemic absorption to produce detectable quantities in human milk. Systemically administeredcorticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroidproduction, or cause other untoward effects. SystemicaUy administered sulfonamides are capable ofproducing kernicterus in infants 01 lactating women. Because of the potential for serious adverse reactions
in nursing infants from sulfacetamide sodium and prednisolone acetate ophthalmic suspensions, a decisionshould be made whether to discontinue nursing or to discontinue the medication.
Safety and effectiveness in pediatric patients below the age of six have not been
Adverse reactions have occurred with corticosteroidfantibacterial combination
drugs which can be attributed to the corticosteroid component, the antibacterial component, Of thecombination. Exact incidence figures are not available since no denominator of treated patients is available.Reactions OCCtJrring most·otten:.from the presence·of the-antibecterial ingredient 8f~gic-sensitizatiofts:-
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides inCluding.Stevens-Johnson syndrome, toxic epidennal necrolysis, fulminant hepatic necrosis, agranulocytosis,aplastic anemia, and other blood dysaasias (See WARNINGS).Sulfacetamide sodium may cause local irritation,
The reactions due to the corticosteroid component in decreasing order 01 frequency are: elevation of intraocular pressure (lOP) with possible development of glaucoma and infrequent optic nerve damage,posterior subcapsular cataract formation, and delayed wound healing.Atthough systemic effects are extremely uncommon, there have been rare occurrences of systemichypercorticoidism alter use of topical corticosteroids.
Corticosteroid-containing preparations can also cause acute anterior uveitis or perforation of the globe.Mydriasis, loss of eccommodation and ptosis have occasionally been reported lolbwing loCal use ofcorticosteroids.
The development of serondary infection has oocurred after use of combinations
containing corticosteroids and antibacterials. Fungal and viral infections of the cornea are partia.darty proneto develop coincidentally with Iong·term applications of corticosteroid. The possibility of fungal invasion mustbe considered in any persistent corneal ulceration where corticosteroid treatment has been used.
Secondary bacterial ocular infection following suppression 01 host responses also occurs.
DOSAGE AND ADMINISTRATION:
SHAKE WELl8EFQRE USING. Two drops should be instilled into the
conjunctival sac every four hours during the day and at bedtime.
Not more than 20 milHliters should be prescribed initially, and the prescription should not be refilled withoutfurther evaluation as outlined in PRECAUTIONS above.
BLEPHAMIDi:S dosage may be reduced, but care should be taken not to discontinue therapy prematurely.In chronic conditions, withdrawal of treatment should be carried out by gradually decreasing the frequencyof application.
If signs and symptoms fail to improve after two days, the patient should be re-evaluated (seePRECAUTIONS).
8LEPHAMIDE (sulfacetamide sodium-predisolone acetate ophthalmic suspension, USP)is supplied as 5 ml sterile in 10 ml opaque white plastic LOPE bottles and white dropper ups with whiteHOPE caps.
Protect from freezing. Shake wen before using.
Store at temp. not exceeding 25″C (77″F) in an upright position.
PROTECT FROM LIGHT.Sulfonamide solutions darken on prolonged standing and exposure to heat and light. Do not use if solutionhas oareenee. Yellowing does not aflec1 activity.
KEEP OUT OF REACH OF CHILDREN
Manufactared by :
ltyEGYPTlAN INT. PHARMACEunCAL INDUSTRIES CO.
10th OF RAMAOAN CfIY. INDUSIlUAL AREA B1., P.O. BOX= 149 TENTH. EGYPT.
UNDER UCENSE FROM AU£RGAN U.S.A.