Dexachlor

DESCRIPTION

Ophthalmic solution Dexachlor (Dexamethasone Sodium Phosphate) in the 5 mL dispenser bottle is a topical steroid solution containing dexamethasone sodium phosphate equivalent to 1 mg (0.1%) dexamethasone phosphate and 5 mg (0.1%) chloramphenicol in each milliliter of buffered solution. Phenylmercury nitrate 0.02% added as preservative. Dexamethasone sodium phosphate is 9-fluoro-11-b,17-dihydroxy-16alpha-methyl-21-(phosphonooxy)pregna-1,4-diene-3,20-dione disodium salt. Its empirical formula is C22H28FNa2O8P. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic. Dexamethasone is a synthetic analog of naturally occurring glucocorticoids (hydrocortisone and cortisone). Dexamethasone sodium phosphate is a water soluble, inorganic ester of dexamethasone. It is approximately three thousand times more soluble in water at 25°C than hydrocortisone. Its molecular weight is 516.41.

Chloramphenicol is D-threo-(-)-2,2-Dichloro-N-(b-hydroxy-a-(hydroxymethyl)-p-nitrophenethyl) acetamide.

ACTIONS/CLINICAL PHARMACOLOGY

* Dexamethasone sodium phosphate suppresses the inflammatory response to a variety of agents and it probably delays or slows healing. No generally accepted explanation of these steroid properties have been advanced.

* Chloramphenicol has a wide spectrum of antimicrobial activity and is effective against many gram-negative and gram- positive organisms such as ESCHERICHIA COLI, HAEMOPHILUS INFLUENZAE, STAPHYLOCOCCUS AUREUS, STREPTOCOCCUS HEMOLYTICUS, and MORAXELLA LACUNATA (Morax-Axenfeld bacillus).

INDICATIONS AND USAGE

* Steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe, such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitis when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation; corneal injury from chemical or thermal burns, or penetration of foreign bodies.

* Chloramphenicol is indicated for the treatment of superficial ocular infections involving the conjunctiva and/or cornea caused by chloramphenicol-susceptible organisms.

CONTRAINDICATIONS

* Epithelial herpes simplex keratitis (dendritic keratitis).

* Acute infectious stages of vaccinia, varicella, and many other viral diseases of the cornea and conjunctiva.

* Mycobacterial infection of the eye.

* Fungal diseases of ocular or auricular structures.

* Hypersensitivity to any component of this product, including sulfites (see WARNINGS).

* Perforation of a drum membrane.

* Hypersensitivity to chloramphenicol.

WARNINGS

Prolonged use may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and 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 topical corticosteroids. In acute purulent conditions of the eye or ear, corticosteroids 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 corticosteroid medication in the treatment of herpes simplex other than epithelial herpes simplex keratitis, in which it is contraindicated, requires great caution; periodic slit-lamp microscopy is essential.

Ophthalmic Solution Dexachlor contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

As with other antibiotics, prolonged use may result in overgrowth of non-susceptible organisms. If superinfection occurs, or if clinical improvement is not noted within a reasonable period, discontinue use and institute appropriate therapy. Sensitivity reactions such as stinging, itching, angioneurotic edema, urticaria, vesicular and maculopapular dermatitis may also occur in some patients. Occasionally one sees hematopoietic toxicity with the use of systemic chloramphenicol, and rarely with topical administration. This type of blood dyscrasia is generally a dose-related toxic effect on bone marrow and is usually reversible on cessation of the drug. Rare cases of aplastic anemia have been reported with prolonged (months to years) or frequent intermittent (over months and years) use of topical chloramphenicol.

PRECAUTIONS

General

The possibility of persistent fungal infections of the cornea should be considered after prolonged corticosteroid dosing.

There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. (See PRECAUTIONS, Information For Patients.)

Information For Patients

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.

Patients should also be instructed that ocular solutions, 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 solutions. (See PRECAUTIONS, General)

Patients should also be advised that if they develop an intercurrent ocular condition (e.g., trauma, ocular surgery or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container.

One of the preservatives in Ophthalmic Solution Dexachlor, phenylmercury nitrate, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling Ophthalmic Solution Dexachlor before they insert their lenses.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of Ophthalmic Solution Dexachlor.

Pregnancy

Pregnancy Category C: Dexamethasone has been shown to be teratogenic in mice and rabbits following topical ophthalmic application in multiples of the therapeutic dose.

In the mouse, corticosteroids produce fetal resorptions and a specific abnormality, cleft palate.

In the rabbit, corticosteroids have produced fetal resorptions and multiple abnormalities involving the head, ears, limbs, palate, etc.

There are no adequate or well-controlled studies in pregnant women. Ophthalmic Solution Dexachlor should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism.

Nursing Mothers

Topically applied steroids are absorbed systemically. Therefore, because of the potential for serious adverse reactions in nursing infants from dexamethasone sodium phosphate, a decision should be made whether to discontinue nursing or 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.

ADVERSE REACTIONS

* Glaucoma with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex,

perforation of the globe.

* Rarely, filtering blebs have been reported when topical steroids have been used following cataract surgery.

* Rarely, stinging or burning may occur.

* The most serious reaction reported following prolonged or frequent intermittent use of topical chloramphenicol is bone marrow aplasia.

DOSAGE AND ADMINISTRATION

The duration of treatment will vary with the type of lesion and may extend from a few days to several weeks, according to therapeutic response. Relapses, more common in chronic active lesions than in self-limited conditions, usually respond to retreatment.

Instill one or two drops of solution into the conjunctival sac every hour during the day and every two hours during the night as initial therapy. When a favorable response is observed, reduce dosage to one drop every four hours. Later, further reduction in dosage to one drop three or four times daily may suffice to control symptoms.

HOW SUPPLIED

Sterile Ophthalmic Solution Dexachlor is a clear, colorless to pale yellow solution.

Dexachlor is supplied in 5 mL white, opaque, plastic ophthalmic dispenser bottle with a controlled drop tip.

REFRIGERATE UNTIL DISPENSED.