Prednicarbate is a topical, low- to medium-potency, synthetic non-fluorinated and non-halogenated corticosteroid. It is similar in potency to hydrocortisone. It is used to relieve the inflammatory and pruritic manifestations of mild to moderate corticosteroid-responsive dermatoses. Prednicarbate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The cream may be used in pediatric patients 1 year of age and older, although the safety and efficacy of use for longer than 3 weeks has not been established. Prednicarbate was initially approved by the FDA in 1991.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-For external application to the skin only. Not for ophthalmic or intravaginal use.
-Occlusive Dressing Technique: Apply a thin film of ointment to the lesion. For the cream, gently rub a small amount into the lesion until it disappears then reapply, leaving a thin coating on the lesion. Cover the lesion with a pliable, nonporous film and seal the edges. If additional moisture is needed, apply a dampened clean cotton cloth before the nonporous film is applied or briefly wet the affected area with water immediately prior to applying the medication. The frequency of dressing changes is best determined on an individual basis. It may be convenient to apply prednicarbate under an occlusive dressing in the evening and remove the dressing in the morning (i.e. 12 hour occlusion). When utilizing the 12 hour occlusion regimen, additional prednicarbate should be applied, without occlusion, during the day. Reapplication is essential at each dressing change. If an infection develops, the use of occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.
Cream/Ointment/Lotion Formulations:
-Cream or ointment: 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, do not wash or rub the treated area or apply clothing. Hair may be washed as usual during the treatment period, but not immediately after applying the medication.
The following adverse reactions (listed in decreasing order of occurrence) are reported with topical corticosteroids such as prednicarbate and may occur more often when used with an occlusive dressing: skin irritation (including burning or edema), pruritus, xerosis (dry skin), folliculitis, erythema, hypertrichosis, acneiform rash/eruptions, skin hypopigmentation, perioral dermatitis, allergic maceration of the skin, secondary infection, skin atrophy, striae, telangiectasia (5% of 59 patients, but prior use of topical corticosteroids may have been a contributing factor), and miliaria. Maculopapular rash (< 1%) and purpura may also occur. Although skin atrophy usually occurs after prolonged use of prednicarbate, this effect may occur even with short-term use of prednicarbate on intertriginous or flexor areas, or on the face. Mild signs of skin atrophy such as shininess and thinness were noted in 1% of adults and in 8% of 59 children. If irritation develops, discontinue topical corticosteroids and institute appropriate therapy. The anti-inflammatory activity of topical corticosteroids may also mask manifestations of infection. In the presence of dermatological infections, institute the use of an appropriate antifungal or antibacterial agent. If a favorable response does not promptly occur, discontinue the corticosteroid until the infection has been adequately controlled.
Signs and symptoms of corticosteroid withdrawal may occur with prednicarbate dose reduction or discontinuation, and supplemental systemic corticosteroids may be needed. For example, disease flare may occur and HPA axis suppression may be present.
Systemic absorption of topical corticosteroids such as prednicarbate can produce reversible hypothalamic-pituitary-adrenal (HPA) suppression with possible adrenocortical insufficiency after stopping treatment. Significant HPA-axis suppression was not noted with use of either 0.1% ointment 60 grams/day for a week or 0.1% cream 30 grams/day for a week in adults with extensive psoriasis or atopic dermatitis. Also, twice daily use of the 0.1% cream for 3 weeks to > 20% of the body surface area of 59 children with extensive atopic dermatitis did not produce HPA-axis suppression. In some patients, systemic absorption can produce manifestations of Cushing's syndrome, hypertension, hyperglycemia, and glycosuria. Percutaneous absorption of prednicarbate is dependent on many factors including the vehicle, the integrity of the epidermal barrier, duration of use, and use of an occlusive dressing. Children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. Manifestations of adrenocortical insufficiency in children include linear growth inhibition and delayed weight gain. Increased intracranial pressure has also been reported in children receiving topical corticosteroids; manifestations of increased intracranial pressure include bulging fontanelles, headache, and bilateral papilledema (i.e., pseudotumor cerebri). Patients applying prednicarbate to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression (using the ACTH stimulation test, AM plasma cortisol test, and urinary free cortisol test). To minimize risk of HPA axis suppression, discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, reduce the frequency of application, or substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid.
Case reports describe visual impairment patients using topical corticosteroids like prednicarbate for eczema of the face. The visual impairment was secondary to the onset of ocular hypertension. Such adverse effects, if they occur, could lead to blindness. Cataracts have also been reported, usually with large doses or therapy > 6 months. Any patient who develops changes in vision during topical corticosteroid therapy such as prednicarbate should be evaluated for ocular hypertension. Low potency corticosteroids (e.g., hydrocortisone, dexamethasone) have been reported to be safer for short-term use around the eye area.
In general, excessive use of corticosteroids can lead to impaired wound healing. Since prednicarbate is a topical corticosteroid, it should not be applied directly or near healing wounds. A propensity for skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.
Tolerance may occur with the prolonged use of topical corticosteroids like prednicarbate. Tolerance is usually described as a decreased acute vasoconstrictive response to the agent after a period of days to weeks. This may explain the dramatic responses noted initially by patients early in topical corticosteroid treatment and an apparent diminished response with time. Tolerance is reversible and may be attenuated by interrupted or cyclic schedules of application.
Allergic contact dermatitis with corticosteroids such as prednicarbate is usually diagnosed by observing a failure to heal. Appropriate diagnostic patch testing may help with the diagnosis.
Prednicarbate is contraindicated in any patient with a history of prednicarbate hypersensitivity or hypersensitivity to any ingredients in the preparation. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to prednicarbate should not receive any form of prednicarbate. 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.
Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions which increase systemic absorption include application of very high-potency corticosteroids, use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of an occlusive dressing. Patients receiving large doses of a potent topical corticosteroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression using ACTH stimulation, morning plasma cortisol, and urinary free-cortisol tests. 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. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids. Due to the potential for glucose alterations, prednicarbate should be used cautiously in patients with diabetes mellitus.
There are no adequate and well-controlled studies of topical application of prednicarbate during pregnancy. Topical corticosteroids, including prednicarbate, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women. Guidelines recommend mild to moderate potency agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birthweight has been reported with use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.
It is not known whether topical administration of prednicarbate could result in sufficient systemic absorption to produce detectable quantities in breast milk. However, most dermatologists stress that topical corticosteroids can be safely used during lactation. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. Consider therapy with less-potent topical agents, like hydrocortisone or triamcinolone, in nursing mothers requiring long-term therapy with a topical corticosteroid. 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.
The normal inflammatory response to local infections can be masked by prednicarbate. Application of topical corticosteroids to areas of infection, including tuberculosis of the skin, dermatologic fungal infection, and cutaneous or systemic viral infection (i.e., herpes infection, measles or varicella), should be initiated or continued only if the appropriate antiinfective treatment is instituted. Herpes infections may be transmitted to other sites, including the eye. If the infection does not respond to the antimicrobial therapy, the concurrent use of the topical corticosteroid should be discontinued until the infection is controlled. Topical corticosteroids may delay the healing of non-infected wounds, such as venous stasis ulcers.
Prednicarbate should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis. Prednicarbate may aggravate these conditions. Prednicarbate preparations are not for vaginal administration and should not be applied to the face, groin, or axillae. Care should be taken to avoid use around the eyes; ophthalmic administration should be avoided. Visual impairment and ocular hypertension have been reported with ocular exposure to other high potency topical corticosteroids. High potency corticosteroids have been noted to promote progression of cataracts. Preexisting glaucoma may be aggravated if prednicarbate is used in the periorbital area.
Topical corticosteroids 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 prednicarbate preparations cautiously in patients with markedly impaired circulation or peripheral vascular disease due to the potential for skin ulcer. Use of lower potency topical corticosteroids also may be necessary in some patients.
Prednicarbate may be used with caution in children 1 year of age or older; the safety and efficacy of drug use for longer than 3 weeks have not been established. Safety and efficacy of prednicarbate in infants and neonates below 1 year of age have not been established and use in this age group is not recommended. Administration of topical prednicarbate to children should be limited to the least amount compatible with an effective therapeutic regimen. Children, infants, and neonates may absorb proportionally larger amounts of topical corticosteroids due to a larger skin surface area to body weight ratio, and therefore are more susceptible to developing systemic toxicity, especially with very-high-potency products. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, growth inhibition (linear growth retardation and delayed weight gain), and increased intracranial pressure have been reported in children receiving topical corticosteroids. Prednicarbate should not be used to treat diaper dermatitis. If children are being treated 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.
For the treatment of corticosteroid-responsive dermatoses [e.g., alopecia areata, atopic dermatitis, contact dermatitis, exfoliative dermatitis, contact dermatitis including Rhus dermatitis due to poison ivy, discoid lupus erythematosus (facial and juxtaposed skin surface areas), eczema, granuloma annulare, keloids (reduction of associated itching), cutaneous lichen planus, lichen simplex chronicus, lichen striatus, polymorphous light eruption, pompholyx (dyshidrosis), necrobiosis lipoidica diabeticorum, pemphigus, pityriasis rosea, nodular prurigo, anogenital or senilis pruritus, psoriasis, sarcoidosis, seborrheic dermatitis (facial and juxtaposed skin surface areas), or xerosis (inflammatory phase)]:
NOTE: Acute exudative inflammation, as occurs with poison ivy, may be best treated with the cream formulation, which is drying. Dry, scaly dermatoses, as occur with eczema or psoriasis, may be best treated with the ointment formulation.
NOTE: Occlusive dressings may be required for chronic or severe cases of lichen simplex chronicus, psoriasis, eczema, atopic dermatitis, or chronic hand eczema. More potent topical corticosteroids and/or occlusive dressings may be necessary for the treatment of discoid lupus erythematosus, lichen planus, granuloma annulare, psoriatic plaques, and psoriasis of the palms, soles, elbows, or knees. This procedure should be done only as directed by a physician.
-for the general treatment of corticosteroid-responsive dermatoses:
Topical dosage (cream):
Adults: Apply a thin film topically to the affected skin area(s) 2 times daily. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassess diagnosis.
Children and Adolescents: Apply a thin film topically to the affected skin area(s) 2 times daily. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassess diagnosis.
Topical dosage (ointment):
Adults: Apply a thin film topically to the affected skin area(s) 2 times daily.
Children and Adolesents 10 to 17 years: Apply a thin film topically to the affected skin area(s) 2 times daily.
-for the treatment of psoriasis:
Topical dosage (cream):
Adults: Apply a thin film topically to the affected skin area(s) 2 times daily. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassess diagnosis. The duration of the therapy depends on factors such as the topical corticosteroid potency, disease severity and anatomic location, and age. After improvement, may consider transitioning to lower-potency corticosteroid, using intermittent therapy, and combining treatment with noncorticosteroidal agents. Taper by reducing use to every other day, then twice weekly, then discontinue if adequate control is maintained. Guidelines recommend class 1 to 5 topical corticosteroids for up to 4 weeks for plaque psoriasis not involving intertriginous areas and class 1 to 7 topical corticosteroids for a minimum of up to 4 weeks for scalp psoriasis. Use of topical corticosteroids for more than 12 weeks may be considered under careful supervision.
Children and Adolescents: Apply a thin film topically to the affected skin area(s) 2 times daily. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassess diagnosis. Guidelines recommend topical corticosteroids as monotherapy for short-term treatment of localized psoriasis.
Topical dosage (ointment):
Adults: Apply a thin film topically to the affected skin area(s) 2 times daily. The duration of the therapy depends on factors such as the topical corticosteroid potency, disease severity and anatomic location, and age. After improvement, may consider transitioning to lower-potency corticosteroid, using intermittent therapy, and combining treatment with noncorticosteroidal agents. Taper by reducing use to every other day, then twice weekly, then discontinue if adequate control is maintained. Guidelines recommend class 1 to 5 topical corticosteroids for up to 4 weeks for plaque psoriasis not involving intertriginous areas and class 1 to 7 topical corticosteroids for a minimum of up to 4 weeks for scalp psoriasis. Use of topical corticosteroids for more than 12 weeks may be considered under careful supervision.
Children and Adolesents 10 to 17 years: Apply a thin film topically to the affected skin area(s) 2 times daily. Guidelines recommend topical corticosteroids as monotherapy for short-term treatment of localized psoriasis.
Maximum Dosage Limits:
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.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no topical dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
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. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.
Prednicarbate is applied topically as a cream or ointment. The extent of percutaneous absorption of the topical corticosteroids is dependent on many factors, including the pharmaceutical vehicle and the integrity of the epidermis. Metabolism of prednicarbate occurs primarily in the skin, but the portion of the dose that reaches the systemic circulation is metabolized primarily in the liver and excreted renally. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
-Route-Specific Pharmacokinetics
Topical Route
After topical application, absorption of prednicarbate 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 prednicarbate enhances penetration into the skin, and may increase the chance of systemic absorption. Ointments have a hydrating effect, are lipophilic, and may enhance the penetration of prednicarbate into the skin. Anti-inflammatory effects are usually not seen for hours after prednicarbate application, since the mechanism of action requires alterations in synthesis of proteins. Repeated application results in a cumulative depot effect in the skin, which may lead to a prolonged duration of action and increased systemic absorption.