DERMATOP Ointment, Cream Ref.[49818] Active ingredients: Prednicarbate

Warnings

When used under occlusive dressing, over extensive areas, or on the face, scalp, axillae and scrotum, sufficient absorption of the topical corticosteroid may occur, giving rise to adrenal suppression and other systemic effects.

Visual disturbance may be associated with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR).

Precautions

General

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitaryadrenal (HPA) axis suppression. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids.

DERMATOP (prednicarbate ointment/emollient cream, 0.1%) applied to human skin at 30 gm daily for 7 days did not produce any indication of systemic effects on the HPA axis. Conditions which augment systemic absorption include application of the more potent steroids, use over large surface areas, prolonged use, and use of occlusive dressings. Patients receiving a large dose of potent topical steroids to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression. This may be done using ACTH stimulation test or other recognized, validated test. 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 steroid. Recovery of HPA axis is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Occlusive dressings should not be applied if body temperature is elevated.

To minimize systemic absorption when long-term therapy or large surface area for treatment is likely, periodic interruption of treatment or treatment of one area of the body at a time should be considered.

Children may be more susceptible to systemic toxicity from equivalent dosing due to larger skin surface to body mass ratios (see PRECAUTIONS – Pediatric Use).

If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favourable response does not occur promptly, use of DERMATOP should be discontinued until the infection has been adequately controlled.

If irritation develops, DERMATOP should be discontinued and appropriate therapy instituted.

Allergic contact dermatitis from corticosteroids is usually diagnosed by observing “failure to heal” rather than clinical exacerbations as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

Suitable precautions should be taken when using topical corticosteroids in patients with stasis dermatitis and other skin diseases associated with impaired circulation.

Topical corticosteroids, particularly the more potent ones, should be used with caution on lesions close to the eye because systemic absorption may cause increased intraocular pressure, glaucoma or cataracts.

Prolonged use of topical corticosteroid preparations may produce stria or atrophy of the skin or sub-cutaneous tissue. Topical corticosteroids should be used with caution on lesions of the face, groin and axillae as these areas are more prone to atrophic changes than other areas of the body. Frequent observation is important if these areas are to be treated. If skin atrophy is observed, treatment should be discontinued.

Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.

DERMATOP contains a paraffin, which can cause leaking or breaking of latex condoms. Contact between DERMATOP and latex condoms must therefore be avoided.

Use in Pregnancy

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage. Prednicarbate has been shown to be teratogenic and embryotoxic in rats and rabbits when administered subcutaneously.

There are no adequate and well-controlled studies in pregnant women on teratogenic effects of prednicarbate. DERMATOP should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus, particularly in the first trimester of pregnancy. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for hypoadrenalism.

Lactation / Nursing Mothers

Systemically administered corticosteroids are secreted into human milk, and could suppress growth, interfere with endogenous corticosteroid production or cause untoward effects. Caution should be exercised when DERMATOP is administered to a nursing mother.

Pediatric Use

DERMATOP EMOLLIENT CREAM (prednicarbate emollient cream 0.1%) has been shown to be safe and effective in children and infants and is indicated in this population. A systemic tolerance study using this formulation in patients from 4 to 143 months (mean age = 5 years), found no effects on HPA axis function when it was used to treat at least 20% of their total body surface for 21 consecutive days.

The safety and effectiveness of DERMATOP OINTMENT (prednicarbate ointment, 0.1%) in children and infants has not been established. Because of the higher ratio of skin surface area to body mass, children are at a greater risk than adults for HPA axis suppression when treated with topical corticosteroids. They are also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment. Adverse effects including striae have been reported with use of topical corticosteroids in infants and children. HPA axis suppression, Cushing’s syndrome and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches and bilateral papilledema.

Administration of topical corticosteroids to children should be limited to the latest amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

DERMATOP EMOLLIENT CREAM should not be used in the treatment of diaper dermatitis.

Carcinogenesis, Mutagenicity, Reproduction

Long-term animal studies have not been performed to evaluate the carcinogenic potential of prednicarbate. Prednicarbate was not mutagenic in the Salmonella reversion test (Ames test) over a wide range of concentrations in the presence and absence of S-9 microsomal fraction. It was not clastogenic in the mouse micronucleus test when mice were administered doses ranging from 1 to 160 mg/kg of the drug.

Prednicarbate was tested for effects on reproduction. In a study of the effect of prednicarbate on fertility, pregnancy and postnatal development in rats, no effect was noted on the fertility or pregnancy of parent animals or postnatal development of the offspring after administration of up to 0.20 mg/kg/day of prednicarbate subcutaneously. A 0.80 mg/kg/day dose produced slight growth retardation of foetuses and placentas.

Prednicarbate has been shown to be teratogenic and embryotoxic in Wistar rats and Himalayan rabbits when administered subcutaneously during gestation at doses of 2.24 mg/kg/day and 0.018 to 0.056 mg/kg/day respectively during organogenesis.

In the rats, slightly retarded foetal development and an incidence of thickened and wavy ribs higher than the spontaneous rate were noted. In rabbits, increased liver weights and a slight increase in the foetal intrauterine death rate were observed. The foetuses that were delivered exhibited reduced placental weight, increased frequency of cleft palate, ossification disorders in the sternum, omphalocele, and anomalous posture of the forelimbs.

In controlled clinical trials in adults, the total incidence of adverse reactions associated with the use of DERMATOP OINTMENT (prednicarbate ointment 0.1%) was low (1.6%). These adverse reactions were moderate to severe and are listed in decreasing order of occurrence as follows: pruritis (0.6%), burning (0.3%), drying, scaling and cracking of the skin accompanied by pain (0.3%), and irritant dermatitis with increased pruritis (0.3%).

A similar frequency of adverse reactions (1.8%) was associated with the use of DERMATOP EMOLLIENT CREAM (prednicarbate emollient cream, 0.1%) in controlled clinical trials with patients aged 12-86 years. These adverse reactions were usually mild to moderate in severity and listed in decreasing order of occurrence are as follows: pruritis (0.9%), edema (0.4%), burning sensation (0.4%) and rash (0.4%).

In pediatric studies with patients ranging in age from 2 months to 12 years, the frequency of adverse reactions seen with DERMATOP EMOLLIENT CREAM was 5.1%. This was similar to the frequency observed with 1% hydrocortisone cream in the same study (7.8%). Adverse reactions associated with the use of DERMATOP EMOLLIENT CREAM were usually mild in severity and are listed in decreasing order of occurrence as follows: application site reaction (2.8%), skin disorder (1.1%), infection (0.6%) and rash (0.6%).

In a controlled study in pediatric patients with atopic dermatitis, mild signs of atrophy were observed in 3 (3%) of the prednicarbate treated subjects (mild telangiectasia and thinness, mild loss of elasticity, mild shininess) and 1 (1%) of the hydrocortisone treated subjects (mild shininess). In an uncontrolled study in a similar patient population, mild signs of atrophy developed in 5 patients (8%) with 2 patients exhibiting more than one sign. Two patients (3%) developed shininess, and 2 patients (3%) developed thinness. Three patients were observed with mild telangiectasia. It is unknown whether prior use of topical corticosteroids was a contributing factor in the development of telangiectasia in two of the patients.

The following local adverse reactions have been reported infrequently with topical corticosteroids but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of frequency: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, miliaria. In addition, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction of discontinuation of potent topical steroid products. Skin atrophogenic effects (such as skin thinning, skin atrophy, skin discolouration, telangiectasia) may occur with use of DERMATOP for more than three weeks.

Adrenal suppression has been reported following topical corticosteroid therapy. Posterior subcapsular cataracts have been reported following systemic use of corticosteroids.

Eye disorders such as blurred vision and chorioretinopathy have been reported.