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  • CLASSES

    Ophthalmological Corticosteroids
    Otic Corticosteroids
    Plain Topical Corticosteroids
    Topical Scalp Anti-inflammatories, with Corticosteroids

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic, low to medium potency fluorinated corticosteroid
    Used topically to treat corticosteroid-responsive dermatoses
    Used intravitreally for the treatment of chronic non-infectious uveitis and diabetic macular edema

    COMMON BRAND NAMES

    Capex, Derma-Smoothe/FS, DermOtic Oil, Fluonid, Iluvien, Retisert, Synalar

    HOW SUPPLIED

    Capex Topical Shampoo: 12mg
    Capex/Fluocinolone/Fluocinolone Acetonide/Fluonid/Synalar Topical Sol: 0.01%, 12mg
    Derma-Smoothe/FS/Fluocinolone/Fluocinolone Acetonide Topical Oil: 0.01%
    DermOtic Oil/Fluocinolone/Fluocinolone Acetonide Auricular (Otic) Oil: 0.01%
    Fluocinolone/Fluocinolone Acetonide/Synalar Topical Cream: 0.01%, 0.025%
    Fluocinolone/Fluocinolone Acetonide/Synalar Topical Ointment: 0.025%
    Iluvien Intravitreal Insert: 0.19mg
    Retisert Intravitreal Imp: 0.59mg

    DOSAGE & INDICATIONS

    For the treatment of mild to moderate inflammatory manifestations of corticosteroid-responsive dermatitis such as alopecia areata, atopic dermatitis, contact dermatitis, exfoliative dermatitis, Rhus dermatitis due to plants like poison ivy, or seborrheic dermatitis (facial and intertriginous areas), discoid lupus erythematosus (facial and intertriginous areas), eczema, granuloma annulare, intertrigo, cutaneous lichen planus, lichen simplex chronicus, polymorphous light eruption, pompholyx (dyshidrosis), nodular prurigo, anogenital or senilis pruritus, psoriasis (facial and intertriginous areas), or xerosis (inflammatory phase).
    For atopic dermatitis.
    Topical dosage (topical oil)
    Adults

    Apply topically as a thin film to the affected area 3 times per day.

    Adolescents, Children, and Infants 3 months and older

    Moisten skin and apply topically as a thin film to the affected areas twice daily. Do not treat longer than 4 weeks continuously. The FDA-approved use of Derma-Smoothe/FS oil in pediatric patients 3 months and older is limited to patients with moderate to severe atopic dermatitis. Do not apply to the face or diaper area. Avoid application to intertriginous areas.

    For psoriasis of the scalp.
    Topical dosage (topical oil)
    Adults

    Wet or dampen hair and scalp thoroughly prior to use. Apply a thin film of oil once daily, massage well and cover the scalp with the supplied shower cap. Leave on overnight or for a minimum of 4 hours before washing off. Wash hair with regular shampoo and rinse thoroughly. In a vehicle-controlled study, after 21 days of treatment 60% of patients receiving fluocinolone topical oil and 21% of patients receiving drug vehicle achieved a good to excellent clinical response.

    For seborrheic dermatitis of the scalp.
    Topical dosage (shampoo)
    Adults

    No more than one (1) ounce of shampoo should be applied to the scalp area once daily, worked into a lather and allowed to remain on the scalp for approximately 5 minutes. Rinse the hair and scalp completely twice. In vehicle-controlled studies, after 14 days of treatment, 84% of patients on fluocinolone and 29% of patients on drug vehicle had cleared or markedly improved.

    Topical dosage (cream, ointment, or topical solution)
    Adults

    Apply sparingly to the affected area 2 to 4 times per day, depending on the severity of the condition. In hairy sites, the hair should be parted to allow direct contact with the lesion. Occlusive dressings may be used for the management of recalcitrant conditions.

    Children and Adolescents

    Apply sparingly to the affected area 2 to 4 times per day, depending on the severity of the condition. In hairy sites, the hair should be parted to allow direct contact with the lesion. Occlusive dressings may be used for the management of recalcitrant conditions.

    For the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.
    Intravitreal implant dosage (Retisert)
    Adults

    One implant containing 1 tablet of 0.59 mg fluocinolone acetonide is surgically implanted into the posterior segment of the affected eye. Fluocinolone acetonide is initially released at a rate of 0.6 mcg/day, decreasing over the first month to a steady state of 0.3 to 0.4 mcg/day and continues at this rate for approximately 30 months. If there is a recurrence of uveitis after the fluocinolone acetonide has been depleted from the implant, the implant may be replaced.

    For the treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure.
    Intravitreal implant dosage (Iluvien)
    Adults

    Inject the implant (containing 0.19 mg fluocinolone acetonide) intravitreally. Monitor the patient for elevated intraocular pressure and endophthalmitis. The implant is designed to release fluocinolone acetonide at an initial rate of 0.25 mcg/day and lasting 36 months. According to the American Diabetes Association (ADA), intravitreous steroid injections are considered second-line alternative treatment options for central-involved diabetic macular edema (CIDME). These drugs are rarely used as first-line treatment options, because when compared against intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents, steroid therapies are associated with inferior visual acuity outcomes and increased rate of cataracts and glaucoma.

    For the treatment of chronic eczematous otitis externa.
    Otic topical dosage (Otic oil, e.g., DermOtic Oil 0.01%)
    Adults

    5 drops instilled into the affected ear(s) twice daily for 7 to 14 days; not to exceed 14 consecutive days of treatment.

    Children and Adolescents 2 years and older

    5 drops instilled into the affected ear(s) twice daily for 7 to 14 days; not to exceed 14 consecutive days of treatment.

    MAXIMUM DOSAGE

    NOTE: In general, corticosteroid dosage must be individualized and is highly variable depending on the nature and severity of the disease, dosage form selected, and patient age and response.

    Adults

    4 applications/day cream, ointment or topical solution; 3 applications/day topical oil, shampoo; 1 ounce/day topically; 1 Retisert implant approximately every 30 months; 1 Iluvien implant approximately every 36 months.

    Geriatric

    4 applications/day cream, ointment or topical solution; 3 applications/day topical oil, shampoo; 1 ounce/day topically; 1 Retisert implant approximately every 30 months; 1 Iluvien implant approximately every 36 months.

    Adolescents

    4 applications/day cream, ointment or topical solution; 2 applications/day topical oil. Some dosage forms not indicated.

    Children

    >=2 years: 4 applications/day cream, ointment or topical solution; 2 applications/day topical oil. Some dosage forms not indicated.
    < 2 years: 2 applications/day topical oil. Safe and effective use of cream, ointment and topical solution have not been established.

    Infants

    >= 3 months: 2 applications/day topical oil. Safe and effective use of cream, ointment and topical solution have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no topical dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Topical Administration
    Cream/Ointment/Lotion Formulations

    Cream, ointment, or topical solution: Apply sparingly in a thin film and rub gently. When applying to hairy areas, part the hair and apply a small amount to the affected area; rub in gently. Until the medication has dried, protect from washing, clothing, or rubbing. Hair may be washed as usual but not immediately after application.

    Other Topical Formulations

    Shampoo: Empty the contents of the enclosed capsule into the shampoo base prior to dispensing. Shake well prior to use. Apply to the scalp area and work into a lather. The extemporaneously prepared shampoo is stable for 2 months from the time of compounding.
    Topical oil: Shake well before using. For areas other than the scalp: moisten skin; apply a thin film of oil to the affected area and rub in gently. Do not apply to the face or diaper area. Avoid application to intertriginous areas. For use on the scalp: wet or dampen hair and scalp before using; apply a thin film of oil, massage well, and cover the scalp with the supplied shower cap.

    Otic Administration

    Otic oil: The patient should tilt their head so the affected ear is facing up. Pull the earlobe backward and upward and use the supplied ear-dropper to apply the drops. The patient should keep their head tilted for approximately one minute and use a clean cotton ball to remove any excess medication dripping form the ear. Administration may be repeated, if necessary, for the opposite ear.

    Other Administration Route(s)

    Intravitreal Administration
    Retisert:
    Fluocinolone intravitreal implants (Retisert) are surgically implanted into the posterior segment of the affected eye.
    Implants should only be handled by the suture tab, as damage to the implant can result in an increased rate of drug release.
    During implantation, care should be taken avoid sheer forces on the implant that could disengage the silicone cup reservoir (which contains a fluocinolone acetonide tablet) from the suture tab.
    Prolonged hydration may reduce the strength of the adhesive bond between the silicone cup reservoir and the suture tab, indicating a potential for the separation of these components. Monitor the integrity of the implant during ophthalmologic examinations.
    Use aseptic techniques prior to and during the surgical procedure; do not resterilize fluocinolone intravitreal implants by any method.
    Iluvien:
    Optimal placement of the implant is inferior to the optic disc and posterior to the equator of the eye. Measure 4 millimeters inferotemporal from the limbus with the aid of calipers for point of entry into the sclera.
    The exterior of the tray should not be considered sterile. Do not use unit if there are signs of damage to the tray or lid. Do not touch the interior surface when peeling the lid from the tray. Visually check through the viewing window of the preloaded applicator to ensure that there is a drug implant inside.
    With sterile, gloved hands, remove the applicator from the tray touching only the sterile interior tray surface and applicator. The applicator tip must be kept above the horizontal plane prior to injection to ensure that the implant is properly positioned within the applicator.
    Just before inserting the needle into the eye, remove the protective cap and gently push the applicator button down and slide it to the first stop (at the curved black marks alongside the button track). At the first stop, release the button and it should move to the UP position. Do not use the unit if it does not move to the UP position.
    Inspect the tip of the needle to ensure it is not bent.
    Gently displace the conjunctiva so that after withdrawing the needle, the conjunctival and scleral needle entry sites will not align. Avoid contact between the needle and the lid margin or lashes. Insert the needle through the conjunctiva and sclera. To release the implant, while the button is in the UP position, advance the button by sliding it forward to the end of the button track and remove the needle. Do not remove the needle until the button reaches the end of the track.
    Remove the lid speculum and perform indirect ophthalmoscopy to verify placement of the implant, adequate central retinal artery perfusion and absence of any other complications.
    Immediately after the intravitreal injection, monitor the patient for elevation in intraocular pressure (IOP) and endophthalmitis. Appropriate monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy 2 to 7 days following the injection. Instruct patients to promptly report any symptoms suggestive of endophthalmitis.

    STORAGE

    Generic:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Store between 59 to 77 degrees F
    Capex:
    - Product should be used within 2 months after opening
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Derma-Smoothe/FS:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    DermOtic Oil :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Fluonid :
    - Avoid excessive heat (above 104 degrees F)
    - Do not freeze
    - Store between 59 to 77 degrees F
    Iluvien:
    - Store at room temperature (between 59 to 86 degrees F)
    Retisert:
    - Protect from freezing
    - Store between 59 to 77 degrees F
    - Store in original container
    Synalar:
    - Avoid excessive heat (above 104 degrees F)
    - Do not freeze
    - Store between 59 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Cushing's syndrome, hypothalamic-pituitary-adrenal (HPA) suppression, occlusive dressing, skin abrasion

    Systemic absorption of topical corticosteroids such as fluocinolone can produce reversible hypothalamic-pituitary-adrenal (HPA) suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. To minimize risk of HPA axis suppression, patients should be treated for no more than 2 weeks at a time and only small areas should be treated. Conditions that increase systemic absorption include use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of occlusive dressings. Fluocinolone and other fluorinated topical corticosteroids should be used cautiously on areas of the body that have a thin layer of skin. Absorption of topical steroids is markedly increased when these agents are applied to areas such as the axilla, eyelids, face, scalp, or scrotum. Patients applying fluocinolone to a large surface area or to areas under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid.

    Ocular exposure, ophthalmic administration

    Care should be taken to avoid ocular exposure to topical fluocinolone products; ophthalmic administration of topical fluocinolone creams, ointments, topical solutions and topical or otic oils should be avoided.

    Children, growth inhibition, increased intracranial pressure, infants, neonates

    Neonates, infants, children, and adolescents may demonstrate a greater susceptibility to topical corticosteroid induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing's syndrome compared to adult patients because of larger skin surface area to body weight ratio. HPA axis suppression, Cushing's syndrome, and increased intracranial pressure have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include growth inhibition (linear growth retardation and delayed weight gain), low plasma cortisol levels, and absence of response in ACTH stimulation. Manifestations of intracranial hypertension including bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic use may interfere with growth and development. Use topical products with caution in young children; many topical products are not recommended for children less than 2 years of age. If children are being treated topically in the diaper area, tight-fitting diapers or plastic pants should be avoided as these garments may act as an occlusive dressing and increase systemic absorption of the drug. Safety and effectiveness of Retisert fluocinolone ophthalmic inserts have not been established in pediatric patients below the age of 12 years ; the Iluvien insert has not been studied in pediatric patients. The safety and efficacy of fluocinolone oil otic drops have not been established in pediatric patients under 2 years of age.
     

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

    Topical corticosteroids should be used with caution in individuals with dermatological infections; the normal inflammatory response to local infections can be masked by corticosteroids such as fluocinolone. Application of topical corticosteroids to areas of infection, including tuberculosis of the skin, dermatologic fungal infection, and cutaneous or systemic viral infection (e.g., herpes infection, measles, varicella), should be initiated or continued only if the appropriate antiinfective treatment is instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled. Fluocinolone intravitreal implants (Retisert and Iluvien) are contraindicated for use in ocular infection, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, or varicella, as well as ophthalmic bacterial, mycobacterial, viral, and fungal infections. Corticosteroid implants are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection. Corticosteroids reduce resistance to infections; do not perform simultaneous bilateral intravitreal implantation in order to limit the possibility of post-operative bilateral ophthalmic infection or other adverse effects.

    Acne rosacea, acne vulgaris, perioral dermatitis

    High-potency topical corticosteroids should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis. Fluocinolone may aggravate these conditions. Topical corticosteroids may delay the healing of non-infected wounds, such as venous stasis ulcers.

    Diabetes mellitus

    Topical corticosteroids, like fluocinolone, should be used with caution in patients with diabetes mellitus. Exacerbation of diabetes may occur with systemic absorption of the topical corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in diabetic patients.

    Geriatric, skin atrophy

    Topical corticosteroids, like fluocinolone, should be used for brief periods, or under close medical supervision in patients with evidence of pre-existing skin atrophy. Geriatric patients may be more likely to have preexisting skin atrophy secondary to aging. Purpura and skin lacerations that may raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the use of topical corticosteroids in geriatric patients. Use of lower potency topical corticosteroids also may be necessary in some patients.

    Pregnancy

    Fluocinolone is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. However, corticosteroids have been shown to be teratogenic in animals when administered systemically at relatively low dosages. Some corticosteroids have been shown to be teratogenic after dermal application in animals. Thus, topical fluocinolone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

    Breast-feeding

    Caution should be exercised when topical or systemic corticosteroids, like fluocinolone, are prescribed during breast-feeding. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in small quantities and while not likely to have a deleterious effect in most infants, could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Consider therapy with less-potent agents, like hydrocortisone (topical or otic alternative) or triamcinolone (topical alternative), in nursing mothers requiring long-term therapy with a topical corticosteroid. Topical corticosteroids should not be applied to the nipples or surrounding breast area prior to nursing.

    Peanut hypersensitivity

    Derma-Smoothe/FS contains peanut oil. Avoid using this product in patients with peanut hypersensitivity as hypersensitivity reactions have been reported. If wheal and flare type reactions, which may be limited to pruritus, or other manifestations of hypersensitivity develop, the products should be discontinued immediately. In one study, topical fluocinolone 0.01% in peanut oil was well tolerated even in patients with peanut allergic sensitivity. Another article concurred.

    Corticosteroid hypersensitivity

    Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to fluocinolone should not receive any form of fluocinolone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.

    Glaucoma

    The Iluvien fluocinolone intravitreal implant is contraindicated for use in patients with glaucoma who have a cup to disc ratio > 0.8. Patients with an absent or torn posterior capsule of the lens are at increased risk of migration of the intravitreal implant into the anterior chamber.

    ADVERSE REACTIONS

    Severe

    ocular hypertension / Delayed / 34.0-90.0
    visual impairment / Early / 10.0-40.0
    ocular hemorrhage / Delayed / 10.0-40.0
    macular edema / Delayed / 10.0-40.0
    retinal detachment / Delayed / 5.0-9.0
    retinal hemorrhage / Delayed / 5.0-9.0
    renal failure (unspecified) / Delayed / 9.0-9.0
    optic atrophy / Delayed / 2.0-2.0
    skin atrophy / Delayed / Incidence not known
    papilledema / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    wound dehiscence / Delayed / Incidence not known
    endophthalmitis / Delayed / Incidence not known

    Moderate

    cataracts / Delayed / 50.0-90.0
    conjunctival hyperemia / Early / 3.0-40.0
    hypotonia / Delayed / 10.0-40.0
    blurred vision / Early / 10.0-40.0
    anemia / Delayed / 11.0-11.0
    erythema / Early / 1.0-10.0
    photophobia / Early / 2.0-9.0
    ocular inflammation / Early / 5.0-9.0
    blepharitis / Early / 5.0-9.0
    corneal edema / Early / 4.0-9.0
    hyphema / Delayed / 5.0-9.0
    photopsia / Delayed / 5.0-9.0
    conjunctivitis / Delayed / 4.0-4.0
    withdrawal / Early / Incidence not known
    growth inhibition / Delayed / Incidence not known
    hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
    Cushing's syndrome / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    ocular infection / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known

    Mild

    ocular pain / Early / 15.0-90.0
    ocular irritation / Rapid / 8.0-40.0
    ptosis / Delayed / 10.0-40.0
    ocular pruritus / Rapid / 3.0-40.0
    foreign body sensation / Rapid / 3.0-40.0
    xerophthalmia / Early / 10.0-40.0
    blepharedema / Early / 10.0-40.0
    headache / Early / 9.0-33.0
    xerosis / Delayed / 1.0-10.0
    maculopapular rash / Early / 1.0-10.0
    pruritus / Rapid / 1.0-10.0
    skin irritation / Early / 1.0-10.0
    diplopia / Early / 5.0-9.0
    ocular discharge / Delayed / 2.0-9.0
    miliaria / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    folliculitis / Delayed / Incidence not known
    telangiectasia / Delayed / Incidence not known
    striae / Delayed / Incidence not known
    acneiform rash / Delayed / Incidence not known
    infection / Delayed / Incidence not known
    hypertrichosis / Delayed / Incidence not known
    skin hypopigmentation / Delayed / Incidence not known

    DRUG INTERACTIONS

    Benzalkonium Chloride: (Moderate) The use of topical aluminum products (aluminum acetate, Burow's solution or aluminum chloride) with benzalkonium chloride aqueous solutions may be incompatible.
    Empagliflozin; Linagliptin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Linagliptin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Linagliptin; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metyrapone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.

    PREGNANCY AND LACTATION

    Pregnancy

    Fluocinolone is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. However, corticosteroids have been shown to be teratogenic in animals when administered systemically at relatively low dosages. Some corticosteroids have been shown to be teratogenic after dermal application in animals. Thus, topical fluocinolone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

    Caution should be exercised when topical or systemic corticosteroids, like fluocinolone, are prescribed during breast-feeding. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in small quantities and while not likely to have a deleterious effect in most infants, could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Consider therapy with less-potent agents, like hydrocortisone (topical or otic alternative) or triamcinolone (topical alternative), in nursing mothers requiring long-term therapy with a topical corticosteroid. Topical corticosteroids should not be applied to the nipples or surrounding breast area prior to nursing.

    MECHANISM OF ACTION

    Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. With topical application to affected skin, these actions correspond to decreased edema, erythema, pruritus, plaque formation, and scaling. With topical ophthalmic application, these actions correspond to decreased edema, capillary dilatation, migration of leukocytes, fibrin and collagen deposition, and scar formation associated with inflammation; it may also reduce capillary and fibroblast proliferation. Ocular application of corticosteroids also results in potentiation of epinephrine vasoconstriction, decreased macrophage movement, and stabilization of lysosomal membranes. Corticosteroids are able to increase intraocular pressures, the degree of which is related to the relative potency of the agent employed, as well as the concentration of the agent and the release from the pharmaceutical vehicle. Decreases in vascularization and scarring make these agents useful in limiting tissue damage in chemical and thermal exposures.

    PHARMACOKINETICS

    Fluocinolone is applied topically as a cream, ointment, solution, shampoo or topical oil and can be for ophthalmic use as an intravitreal implant. Anti-inflammatory effects are usually not seen for hours after fluocinolone application, since the mechanism of action requires alterations in synthesis of proteins. Because fluocinolone is fluorinated and also contains a substituted 17-hydroxyl group, it is not metabolized in the skin. Repeated application results in a cumulative depot effect in the skin, which may lead to a prolonged duration of action and increased systemic absorption. Fluocinolone is metabolized primarily in the liver and excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

    Topical Route

    The extent of percutaneous absorption of the topical corticosteroids is dependent on many factors, including the pharmaceutical vehicle and the integrity of the epidermis. Absorption after topical application of fluocinolone is increased in areas that have skin damage, inflammation, or occlusion, or in areas where the stratum corneum is thin such as the eyelids, genitalia, axillae, and face. The use of occlusive dressings with the application of fluocinolone enhances penetration into the skin, and may increase the chance of systemic absorption. Ointments have a hydrating effect, are lipophilic, and enhance the penetration of clobetasol into the skin. Fluocinolone solutions also have enhanced topical penetration versus cream preparations.

    Other Route(s)

    Ophthalmic Route
    There appears to be minimal systemic absorption following ophthalmic administration. Following intravitreal implantation of one 0.59 mg fluocinolone acetonide tablet (Retisert), fluocinolone acetonide is released at a rate of approximately 0.6 mcg/day, decreasing over the first month to a steady state of 0.3—0.4 mcg/day over approximately 30 months. In this time period, aqueous and vitreous humor concentrations are highly variable. In clinical trials, throughout an observational period of up to 34 months, aqueous and vitreous humor concentrations ranged from below the limit of detection (0.2 ng/mL) to 589 ng/mL. Following intravitreal implantation of a 0.2 mcg/day or 0.5 mcg/day fluocinolone acetonide insert, plasma concentrations of fluocinolone acetonide were below the lower limit of quantitation at all post-administration time points from day 7 through month 36 in a human pharmacokinetic study.