Cortisporin Ophthalmic Suspension

DESCRIPTION

CORTISPORINOphthalmicSuspension (neomycin and polymyxin B sulfates and hydrocortisone ophthalmic suspension) is a sterileantimicrobial和anti-inflammatory suspension for ophthalmic use. Each mL contains: neomycin sulfate equivalent to 3.5 mg neomycin base, polymyxin B sulfate equivalent to 10,000 polymyxin B units, and hydrocortisone 10 mg (1%). The vehicle containsthimerosal0.001% (added as a preservative) and the inactive ingredients cetyl alcohol, glyceryl monostearate, mineral oil, polyoxyl 40 stearate, propylene glycol, and Water for Injection. Sulfuric acid may be added to adjust pH.

Neomycin sulfate is the sulfate salt of neomycin B and C, which are produced by the growth of Streptomyces fradiae Waksman (Fam. Streptomycetaceae). It has a potency equivalent of not less than 600 µg of neomycin standard per mg, calculated on an anhydrous basis. The structural formulae are:

Polymyxin B sulfate is the sulfate salt of polymyxin B₁and 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 mg, calculated on an anhydrous basis. The structural formulae are:

Hydrocortisone, 11β,17,21-trihydroxypregn-4-ene-3,20-dione, is an anti-inflammatory hormone. Its structural formula is:

迹象

CORTISPORIN Ophthalmic Suspension is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial 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 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 (seeCLINICAL PHARMACOLOGY: Microbiology).

The particular anti-infective drugs in this product are active against the following common bacterial eye pathogens:Staphylococcus aureus,Escherichia coli,Haemophilus influenzae,Klebsiella/Enterobacterspecies,Neisseriaspecies, andPseudomonasaeruginosa.

产品不提供足够的覆盖率gainstSerratiamarcescensandstreptococci, includingStreptococcus pneumoniae．

DOSAGE AND ADMINISTRATION

One or two drops in the affected eye every 3 or 4 hours, depending on the severity of the condition. The suspension may be used more frequently if necessary.

Not more than 20 milliliters should be prescribed initially and the prescription should not be refilled without further evaluation as outlined inPRECAUTIONSabove.

SHAKE WELL BEFORE USING.

HOW SUPPLIED

Plastic DROP DOSE® dispenser bottle of 7.5 mL (NDC 61570-036-75).

Store at 15° to 25°C (59° to 77°F).

Prescribing Information as of July 2003. Distributed by: Monarch pharmaceuticals, Inc., Bristol, TN 37620. Manufactured by:DSM制药公司．, Greenville, NC 27834. FDA Rev date: 11/25/2003

SIDE EFFECTS

Adverse reactions have occurred withcorticosteroid/anti-infectivecombination drugs which can be attributed to the corticosteroid component, the anti-infective component, or the combination. The exact incidence is not known.

反应最常发生the presence of theantiinfectiveingredient are allergic sensitization reactions including itching, swelling, andconjunctivalerythema(seeWARNINGS). More serious hypersensitivity reactions, includinganaphylaxis, have been reported rarely.

The reactions due to the corticosteroid component in decreasing order of frequency are: elevation ofintraocular pressure(IOP) with possible development ofglaucoma, and infrequentoptic nervedamage;posteriorsubcapsularcataractformation; and delayed wound healing.

Secondary Infection:The development of secondary infection has occurred after use of combinations containing corticosteroids and antimicrobials. Fungal and viral infections of thecorneaare particularlyproneto develop coincidentally with long-term applications of a corticosteroid. The possibility of fungal invasion must be considered in any persistent cornealulcerationwhere corticosteroid treatment has been used.

Local irritation on instillation has also been reported.

DRUG INTERACTIONS

No information provided.

WARNINGS

NOT FOR INJECTION INTO THE EYE．CORTISPORIN Ophthalmic Suspension should never be directly introduced into theanterior chamberof the eye.

Prolonged use of corticosteroids may result inocularhypertensionand/or glaucoma, with damage to the optic nerve, defects invisual acuityand 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 orsclera, perforations have been known to occur with the use of topical corticosteroids. In acutepurulentconditions of the eye, corticosteroids may mask infection or enhance existing infection.

If these products are used for 10 days or longer,intraocularpressure should be routinely monitored even though it may be difficult in uncooperative patients. Corticosteroids should be used with caution in the presence of glaucoma.

The use of corticosteroids aftercataract surgerymay delay healing and increase the incidence of filtering blebs.

Use of ocular corticosteroids may prolong the course and may exacerbate the severity of many viral infections of the eye (includingherpessimplex). Employment of corticosteroid medication in the treatment of herpes simplex requires great caution.

Topical antibiotics, particularly, neomycin sulfate, may causecutaneoussensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical antibiotics is not known. The manifestations of sensitization to topical antibiotics are usually itching, reddening, and edema of theconjunctivaandeyelid．A sensitization reaction may manifest simply as a failure to heal. During long-term use of topicalantibioticproducts, 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 (seePRECAUTIONS: 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. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated.

The possibility of fungal infections of the cornea should be considered after prolonged corticosteroid dosing. Fungal cultures should be taken when appropriate.

If this product is used for 10 days or longer, intraocular pressure should be monitored (seeWARNINGS).

There have been reports of bacterialkeratitisassociated with the use of topical ophthalmic products in multiple-dose containers which have been inadvertently contaminated by patients, most of whom had a concurrent corneal disease or a disruption of the ocularepithelialsurface (seePRECAUTIONS:Information for Patients).

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:Long- term studies in animals to evaluatecarcinogenicor mutagenic potential have not been conducted with polymyxin B sulfate. Treatment of cultured human lymphocytesin vitrowith neomycin increased the frequency of chromosome aberrations at the highest concentrations (80 µg/mL) tested; however, the effects of neomycin on carcinogenesis andmutagenesisin humans are unknown.

Long-term studies in animals (rats, rabbits, mice) showed no evidence of carcinogenicity or mutagenicity attributable to oral administration of corticosteroids. Long-term animal studies have not been performed to evaluate the carcinogenic potential of topical corticosteroids. Studies to determine mutagenicity with hydrocortisone have revealed negative results.

Polymyxin B has been reported to impair the motility of equinesperm, but its effects on male or female fertility are unknown. Long-term animal studies have not been performed to evaluate the effect on fertility of topical corticosteroids.

Pregnancy: Teratogenic Effects:Pregnancy Category C. Corticosteroids have been found to beteratogenicin rabbits when applied topically at concentrations of 0.5% on days 6 to 18 of gestation and in mice when applied topically at a concentration of 15% on days 10 to 13 of gestation. There are no adequate and well-controlled studies in pregnant women. CORTISPORIN Ophthalmic Suspension (neomycin and polymyxin b sulfates and hydrocortisone opthalmic suspension) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere withendogenouscorticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from CORTISPORIN Ophthalmic Suspension (neomycin and polymyxin b sulfates and hydrocortisone opthalmic suspension) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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.

OVERDOSE

No information provided.

CONTRAINDICATIONS

CORTISPORIN Ophthalmic Suspension is contraindicated in most viral diseases of the cornea and conjunctiva including: epithelial herpes simplex keratitis (dendritickeratitis),vacciniaandvaricella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures.

CORTISPORIN Ophthalmic Suspension (neomycin and polymyxin b sulfates and hydrocortisone opthalmic suspension) is also contraindicated in individuals who have shown hypersensitivity to any of its components. Hypersensitivity to the antibiotic component occurs at a higher rate than for other components.

CLINICAL PHARMACOLOGY

Corticosteroids suppress theinflammatory responseto a variety of agents, and they probably delay or slow healing. Since corticosteroids may inhibit the body's defense mechanism against infection, concomitant antimicrobial drugs 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 antimicrobials 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 all drugs is administered. When each type of drug is 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.

Microbiology:The anti-infective components in CORTISPORIN Ophthalmic Suspension are included to provide action against specific organisms susceptible to it. Neomycin sulfate and polymyxin B sulfate are activein vitroagainst susceptible strains of the following microorganisms:Staphylococcus aureus,Escherichia coli,Haemophilus influenzae,Klebsiella/Enterobacterspecies,Neisseriaspecies, andPseudomonasaeruginosa．产品不提供足够的覆盖率gainstSerratiamarcescensand streptococci, includingStreptococcus pneumoniae(see迹象).

PATIENT INFORMATION

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, eyelid, fingers, or any other surface. The use of this product by more than one person may spread infection.

Patients should also be instructed that ocular products, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated products (seePRECAUTIONS: General).

If the condition persists or gets worse, or if a rash or allergic reaction develops, the patient should be advised to stop use and consult a physician. Do not use this product if you are allergic to any of the listed ingredients.

Keep tightly closed when not in use. Keep out of reach of children.