CLASSES

Plain Topical Corticosteroids

DEA CLASS

Rx

DESCRIPTION

Topical low-to-medium potency synthetic corticosteroid

Equivalent in efficacy to desonide and hydrocortisone

Used for corticosteroid-responsive dermatoses

COMMON BRAND NAMES

Aclovate

HOW SUPPLIED

Aclovate/Alclometasone/Alclometasone Dipropionate Topical Cream: 0.05%

Aclovate/Alclometasone/Alclometasone Dipropionate Topical Ointment: 0.05%

DOSAGE & INDICATIONS

For the treatment of mild to moderate inflammatory manifestations of corticosteroid-responsive dermatitis such as 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, anogenital or senilis pruritus, psoriasis (facial and intertriginous areas), or xerosis (inflammatory phase).

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.

Topical dosage (cream or ointment)

Adults, Adolescents, and Children >= 1 year

Apply a thin film to the affected area 2—3 times/day; massage gently until the medication disappears. An initial response to eczema or psoriasis occurs in 5—7 days, with peak effects by 14 days. If no response is seen within 2 weeks, reassess treatment options. In children, the safety and efficacy of use for more than 3 weeks has not been established.

MAXIMUM DOSAGE

Adults

Maximum dosage information not available.

Elderly

Maximum dosage information not available.

Adolescents

Maximum dosage information not available.

Children

Do not exceed 3 weeks of treatment.

Infants

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Hepatic Impairment

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

For topical dermatologic use only. Not for ophthalmic, oral, or intravaginal use.

Apply a thin film to the affected area and rub in gently but completely.

Occlusive dressings may be used for the management of refractory or chronic dermatoses or more severe conditions. Do not apply to the diaper area if the child still requires diapers or plastic pants as these garments may constitute an occlusive dressing and increase the risk of toxicity.

STORAGE

Aclovate:

- Store between 36 to 86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

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

Systemic absorption of topical preparations may result in hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing's syndrome in some patients. Alclometasone dipropionate has been shown to suppress the HPA axis in pediatric patients receiving twice daily applications for 3 weeks and in patients where 30% of body surface was treated using occlusive dressings. Conditions which 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 an occlusive dressing. Patients receiving large doses of alclometasone applied to a large surface area or 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 substitute a less potent corticosteroid.

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

The safety and efficacy of alclometasone ointment and cream in neonates and infants less than 1 year of age have not been established. Administration of alclometasone to children should be limited to the least amount compatible with an effective therapeutic regimen. Children 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. 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. Pediatric patients applying alclometasone cream or ointment to more than 20% of the body surface area are at higher risk of HPA axis suppression. Alclometasone cream or ointment should not be used for the treatment of 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.

Pregnancy

There are no adequate and well-controlled studies of topical application of alclometasone during pregnancy. Topical corticosteroids, including alclometasone, 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.

Breast-feeding

According to the manufacturer, it is not known whether topical administration of alclometasone could result in sufficient systemic absorption to produce detectable quantities in breast milk during breast-feeding. 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 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.

Acne rosacea, acne vulgaris, fungal infection, herpes infection, infection, measles, perioral dermatitis, tuberculosis, varicella, viral infection

The normal inflammatory response to local infections can be masked by alclometasone. 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 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. Topical corticosteroids should not be used to treat acne vulgaris, acne rosacea or perioral dermatitis as they may aggravated these conditions.

Ocular exposure

Care should be taken to avoid ocular exposure to alclometasone.

Geriatric, skin atrophy

Topical corticosteroids such as alclometasone 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 pre-existing 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.

Diabetes mellitus

Topical corticosteroids such as alclometasone 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.

Corticosteroid hypersensitivity

Alclometasone is contraindicated in any patient with a history of hypersensitivity to any ingredients in the preparation. Use with caution, if at all, in patients with a history of other corticosteroid hypersensitivity. True corticosteroid hypersensitivity is rare. It is possible, though also rare, that patients hypersensitive to alclometasone will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing to determine if hypersensitivity to another corticosteroid exists and should be carefully monitored following the administration of any corticosteroid.

ADVERSE REACTIONS

Severe

skin atrophy / Delayed / Incidence not known

increased intracranial pressure / Early / Incidence not known

papilledema / Delayed / Incidence not known

ocular hypertension / Delayed / Incidence not known

visual impairment / Early / Incidence not known

Moderate

erythema / Early / 1.0-2.0

withdrawal / Early / Incidence not known

growth inhibition / Delayed / Incidence not known

hyperglycemia / Delayed / Incidence not known

pseudotumor cerebri / Delayed / Incidence not known

glycosuria / Early / Incidence not known

hypertension / Early / Incidence not known

adrenocortical insufficiency / Delayed / Incidence not known

Cushing's syndrome / Delayed / Incidence not known

hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known

cataracts / 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

xerosis / Delayed / 2.0-2.0

pruritus / Rapid / 1.0-2.0

skin irritation / Early / 1.0-2.0

maculopapular rash / Early / 2.0-2.0

infection / Delayed / Incidence not known

striae / Delayed / Incidence not known

hypertrichosis / Delayed / Incidence not known

folliculitis / Delayed / Incidence not known

miliaria / Delayed / Incidence not known

acneiform rash / Delayed / Incidence not known

telangiectasia / Delayed / Incidence not known

skin hypopigmentation / Delayed / Incidence not known

purpura / Delayed / Incidence not known

headache / Early / Incidence not known

DRUG INTERACTIONS

Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.

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

There are no adequate and well-controlled studies of topical application of alclometasone during pregnancy. Topical corticosteroids, including alclometasone, 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.

According to the manufacturer, it is not known whether topical administration of alclometasone could result in sufficient systemic absorption to produce detectable quantities in breast milk during breast-feeding. 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 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

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. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.

PHARMACOKINETICS

Alclometasone is applied topically as a cream or ointment. Once in the systemic circulation, alclometasone is metabolized in the liver, but systemic metabolism has not been fully quantified. After hepatic metabolism, alclometasone metabolites are excreted by the kidney.

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. In normal volunteers, approximately 3% of the alclometasone dose is absorbed during 8 hours of contact with intact skin. Absorption after topical application of alclometasone 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 alclometasone 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 alclometasone into the skin. Because alclometasone 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. Circulating levels of alclometasone are normally below the level of detection.