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  • CLASSES

    Ophthalmological Corticosteroids

    DEA CLASS

    Rx

    DESCRIPTION

    Ophthalmic corticosteroid
    Used for postoperative ocular pain and inflammation and endogenous anterior uveitis
    Safety and efficacy comparable to betamethasone 0.1% ophthalmic solution

    COMMON BRAND NAMES

    Durezol

    HOW SUPPLIED

    Durezol Ophthalmic Emulsion: 0.05%

    DOSAGE & INDICATIONS

    For the treatment of postoperative ocular pain and postoperative ocular inflammation.
    Ophthalmic dosage
    Adults

    Instill 1 drop into the conjunctival sac of the affected eye(s) 4 times daily beginning 24 hours after surgery; continue giving 4 times/day for the first 2 weeks of the postoperative period, then administer 2 times daily for 1 week. At the end of the third week, taper dose based on response.

    Infants, Children, and Adolescents

    Instill 1 drop into the conjunctival sac of the affected eye(s) 4 times daily beginning 24 hours after surgery; continue giving 4 times/day for the first 2 weeks of the postoperative period, then administer 2 times daily for 1 week. At the end of the third week, taper dose based on response. In a double-blind trial in pediatric patients (aged 0 to 3 years) who underwent cataract surgery, a similar safety profile was observed in patients who received difluprednate 0.05% (n = 39) compared to those who received prednisolone acetate ophthalmic suspension 1% (n = 40).

    For the treatment of endogenous anterior uveitis.
    Ophthalmic dosage
    Adults

    Instill 1 drop into the conjunctival sac of the affected eye(s) 4 times daily for 14 days followed by tapering as clinically indicated.

    MAXIMUM DOSAGE

    Adults

    4 drops/day in each affected eye.

    Geriatric

    4 drops/day in each affected eye.

    Adolescents

    4 drops/day in each affected eye.

    Children

    4 drops/day in each affected eye.

    Infants

    4 drops/day in each affected eye.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage guidelines are available; it appears no dosage adjustment is needed.

    Renal Impairment

    No dosage guidelines are available; it appears no dosage adjustment is needed.

    ADMINISTRATION

     
    NOTE: Care should be taken not to discontinue therapy prematurely. If ocular signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. Intraocular pressure should be monitored after 10 days of therapy, and an ophthalmologic exam should occur after 14 days of therapy.

    Ophthalmic Administration

    Difluprednate is administered topically to the eye. Shake well before use.
    Do not to touch the tip of the dropper to the eye, fingertips, or other surface.
    Instruct patient on proper instillation of eye solution.
    When using difluprednate, the patient should not wear contact lenses.

    STORAGE

    Durezol :
    - Protect from freezing
    - Protect from light
    - Store between 59 to 77 degrees F
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Corticosteroid hypersensitivity, glycerin hypersensitivity, polysorbate 80 hypersensitivity

    Difluprednate is contraindicated in individuals with glycerin hypersensitivity, hypersensitivity to difluprednate, corticosteroid hypersensitivity, polysorbate 80 hypersensitivity, or any of the other product ingredients (boric acid, castor oil, polysorbate 80, sodium acetate, sodium EDTA, sodium hydroxide).

    Fungal infection, herpes simplex keratitis (dendritic keratitis), mycobacterial infection, ocular infection, varicella, viral infection

    The use of ocular steroids may prolong the course and exacerbate the severity of ocular infections. Ophthalmic steroid use may result in delayed or impaired wound healing of the eye or cornea, or mask the signs of ocular infection. Difluprednate, as with other ophthalmic corticosteroids, is contraindicated in most cases of viral infection of the cornea and conjunctiva, such as epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella. Difluprednate is also contraindicated in any mycobacterial infection of the eye or fungal infection of ocular structures. Fungal infections of the cornea may develop with long-term ocular application of steroids. Fungal invasion should be evaluated in any persistent corneal ulceration where corticosteroid treatment has been used. Fungal cultures should be taken when appropriate. Corticosteroid therapy can also exacerbate purulent bacterial infections of the eye.

    Glaucoma, increased intraocular pressure, open-angle glaucoma

    Increased intraocular pressure (intraocular hypertension) is most likely to occur in patients receiving prolonged ophthalmic corticosteroids and in patients with glaucoma. Intraocular pressure elevations are usually greater in eyes with open-angle glaucoma. If difluprednate is used for 10 days or longer, intraocular pressure should be monitored.

    Cataracts, diabetes mellitus

    Long-term ocular administration of corticosteroids, like difluprednate, for several years has been associated with the formation of posterior subcapsular (PSC) cataracts. Patients with diabetes mellitus appear to be more susceptible to developing PSC cataracts during ocular steroid use. Patients should be monitored for the development of lens opacities during long-term corticosteroid therapy.

    Corneal abrasion

    In patients with corneal or scleral thinning, administration of topical ophthalmic corticosteroids has caused perforations. Difluprednate should be used with caution in patients with a corneal abrasion.

    Contact lenses

    Patients who wear contact lenses should be aware that Durezol (difluprednate) contains the preservative sorbic acid. As with all ophthalmic preparations containing a preservative, patients should be advised not to wear contact lenses when using Durezol.

    Pregnancy

    Difluprednate is classified as pregnancy category C. Animal studies using subcutaneous doses produced teratogenic and embryotoxic effects. Other corticosteroids have been shown to cause fetal resorptions and malformations. The systemic absorption of difluprednate following ophthalmic administration is minimal; however, according to the manufacturer, because there have been no adequate studies conducted into the safe use of difluprednate in pregnant women, it should only be used when the potential benefits to the mother outweigh possible risks to the fetus.

    Breast-feeding

    Difluprednate has not been studied during breast feeding. While the American Academy of Pediatrics does not comment on the use of ophthalmic difluprednate during breast-feeding, it does consider some systemic corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding. It is not known whether ophthalmic difluprednate results in sufficient systemic absorption to produce detectable quantities in breast milk; but pharmacokinetic studies indicate that systemic absorption after ophthalmic administration of difluprednate is limited and therefore unlikely that a significant amount of drug would be excreted into breast-milk. To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    uveitis / Delayed / 0-10.0
    ocular hypertension / Delayed / 1.0-10.0
    keratitis / Delayed / 1.0-10.0
    visual impairment / Early / 1.0-5.0
    macular edema / Delayed / 0-1.0

    Moderate

    conjunctival hyperemia / Early / 5.0-15.0
    blepharitis / Early / 5.0-15.0
    hyperemia / Delayed / 0-15.0
    corneal edema / Early / 2.0-15.0
    photophobia / Early / 2.0-15.0
    blurred vision / Early / 5.0-10.0
    iritis / Delayed / 1.0-10.0
    ocular inflammation / Early / 1.0-5.0
    cataracts / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    ocular infection / Delayed / Incidence not known

    Mild

    ocular pain / Early / 5.0-15.0
    ocular irritation / Rapid / 0-10.0
    xerophthalmia / Early / 2.0-5.0
    lacrimation / Early / 0-1.0
    foreign body sensation / Rapid / 0-1.0
    striae / Delayed / 0-1.0
    ocular pruritus / Rapid / 0-1.0

    DRUG INTERACTIONS

    There are no drug interactions associated with Difluprednate products.

    PREGNANCY AND LACTATION

    Pregnancy

    Difluprednate is classified as pregnancy category C. Animal studies using subcutaneous doses produced teratogenic and embryotoxic effects. Other corticosteroids have been shown to cause fetal resorptions and malformations. The systemic absorption of difluprednate following ophthalmic administration is minimal; however, according to the manufacturer, because there have been no adequate studies conducted into the safe use of difluprednate in pregnant women, it should only be used when the potential benefits to the mother outweigh possible risks to the fetus.

    Difluprednate has not been studied during breast feeding. While the American Academy of Pediatrics does not comment on the use of ophthalmic difluprednate during breast-feeding, it does consider some systemic corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding. It is not known whether ophthalmic difluprednate results in sufficient systemic absorption to produce detectable quantities in breast milk; but pharmacokinetic studies indicate that systemic absorption after ophthalmic administration of difluprednate is limited and therefore unlikely that a significant amount of drug would be excreted into breast-milk. To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, deposition of collagen, and scar formation associated with inflammation. There is no generally accepted explanation for the exact mechanism of action for ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
     
    Corticosteroids can increase intraocular pressure. The mechanism by which ophthalmic corticosteroids increase intraocular pressure is not clear. Corticosteroids are associated with the presence of extracellular glycosaminoglycans in ocular trabecular cells, which have been hypothesized to increase the resistance of aqueous outflow.

    PHARMACOKINETICS

    Difluprednate is administered topically to the eye. Difluprednate undergoes deacetylation in vivo to the active metabolite 6 alpha, 9-difluoroprednisolone 17-butyrate (DFB).

    Topical Route

    Limited systemic absorption of difluprednate occurs following daily administration. In clinical pharmacokinetic studies, DFB levels in blood were below the quantification limit (50 ng/mL) at all time points for all subjects after repeat ocular instillation of 2 drops of difluprednate (0.01% or 0.05%) four times daily for 7 days.