Prenacid

Prenacid^® (desonide) Foam, 0.05% is indicated for the treatment of mild to moderate atopic dermatitis in patients 3 months of age and older.

Patients should be instructed to use Prenacid Foam for the minimum amount of time necessary to achieve the desired results because of the potential for Prenacid Foam to suppress the hypothalamicpituitary- adrenal (HPA) axis. Treatment should not exceed 4 consecutive weeks.

Prenacid Foam is not for oral, ophthalmic, or intravaginal use.

A thin layer of Prenacid Foam should be applied to the affected area(s) twice daily. Shake the can before use. Prenacid Foam should be dispensed by inverting the can (upright actuation will cause loss of the propellant which may affect product delivery). Dispense the smallest amount of foam necessary to adequately cover the affected area(s) with a thin layer.

The medication should not be dispensed directly on the face. Dispense in hands and gently massage into affected areas of the face until the medication disappears. For areas other than the face, the medication may be dispensed directly onto the affected area. Take care to avoid contact with the eyes or other mucous membranes.

Patients should dispense the smallest amount of foam necessary to adequately cover the affected area with a thin layer. Therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, reassessment of diagnosis may be necessary. The safety and efficacy of Prenacid Foam has not been established beyond 4 weeks of use. Treatment should not exceed 4 consecutive weeks.

Unless directed by a physician, Prenacid Foam should not be used with occlusive dressings.

None.

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Hypothalamic-Pituitary-Adrenal Axis Suppression

Prenacid Foam has been shown to reversibly suppress the HPA axis.

Topical application of Prenacid Foam may result in systemic absorption and effects including HPA axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, facial swelling, glycosuria, withdrawal, and growth retardation in children. Use of Prenacid Foam for longer than 4 weeks may suppress the immune system.

Conditions that augment systemic absorption include the application of topical corticosteroids over large body surface areas, prolonged use, or the addition of occlusive dressings. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression.

An adrenocorticotropic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.

The effect of Prenacid Foam on HPA axis function was investigated in pediatric subjects in one trial. In this trial, subjects with atopic dermatitis covering at least 25% of their body applied Prenacid Foam twice daily for 4 weeks. Three out of 75 subjects (4%) displayed adrenal suppression after 4 weeks of use based on the cosyntropin stimulation test. The laboratory suppression was transient; all subjects had returned to normal when tested 4 weeks post-treatment.

Pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of Prenacid Foam due to their larger skin surface-to-body mass ratios..

Concomitant therapy with topical corticosteroids should be used with caution because a cumulative effect may occur.

Skin Irritation

Prenacid Foam may cause local skin adverse reactions. If irritation develops, Prenacid Foam should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing.

Concomitant Skin Infections

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

Flammable Contents

The contents of Prenacid Foam include alcohol and propane/butane, which are flammable. Avoid fire, flame, and/or smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

Laboratory Tests

The cosyntropin (ACTH_1-24) stimulation test may be helpful in evaluating patients for HPA axis suppression.

Patient Counseling Information

See FDA-Approved Patient Labeling (PATIENT INFORMATION)

Patients using topical corticosteroids should receive the following information and instructions:

1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes or other mucous membranes. The medication should not be dispensed directly onto the face. Dispense in hands and gently massage into affected areas of the face until the medication disappears. For areas other than the face, the medication may be dispensed directly on the affected area. Wash hands after use.
2. This medication should not be used for any disorder other than that for which it was prescribed.
3. The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician
4. Patients should report any signs of local or systemic adverse reactions to the physician.
5. Patients should inform their physicians that they are using Prenacid Foam if surgery is contemplated.
6. Therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician.
7. Do not use other corticosteroid-containing products while using Prenacid Foam without first consulting your physician.
8. The propellant in Prenacid Foam is flammable. Avoid fire, flame or smoking during and immediately following application.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Prenacid Foam or desonide. The effects of desonide on fertility have not been evaluated.

In a 90-day repeat-dose toxicity study in rats, topical administration of Prenacid Foam at dose concentrations from 0.025% to 0.125% or from 0.075 to 0.375 mg/kg/day of desonide resulted in a toxicity profile consistent with long-term exposure to corticosteroids including adrenal atrophy, histopathological changes in several organ systems indicative of severe immune suppression, and opportunistic fungal and bacterial infections. A no observable adverse effect level (NOAEL) could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk for carcinogenesis.

Topical doses of 0% (foam vehicle), 0.025%, 0.05%, and 0.125% desonide foam were evaluated in a 52-week dermal photocarcinogenicity study (40 weeks of treatment followed by 12 weeks of observation) conducted in albino hairless mice with concurrent exposure to low level ultraviolet radiation. Topical treatment with increasing concentrations of desonide foam did not have an adverse effect in this study. The results of this study suggest that topical treatment with Prenacid Foam did not enhance photocarcinogenicity.

Desonide revealed no evidence of mutagenic potential based on the results of 2 in vitro genotoxicity tests (Ames assay, mouse lymphoma cell assay) and an in vivo genotoxicity test (mouse micronucleus assay).

Use In Specific Populations

Pregnancy

Teratogenic Effects

Pregnancy Category C

There are no adequate and well-controlled trials of Prenacid Foam in pregnant women. Therefore, Prenacid Foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.

No long-term reproductive studies in animals have been performed with Prenacid Foam. Dermal embryofetal development studies were conducted in rats and rabbits with a desonide cream, 0.05% formulation. Topical doses of 0.2, 0.6, and 2.0 g cream/kg/day of a desonide cream, 0.05% formulation or 2.0 g/kg of the cream base were administered topically to pregnant rats (gestational days 6 to 15) and pregnant rabbits (gestational days 6 to 18). Maternal body weight loss was noted at all dose levels of the desonide cream, 0.05% formulation in rats and rabbits. Teratogenic effects characteristic of corticosteroids were noted in both species. The desonide cream, 0.05% formulation was teratogenic in rats at topical doses of 0.6 and 2.0 g cream/kg/day and in rabbits at a topical dose of 2.0 g cream/kg/day. No teratogenic effects were noted for the desonide cream, 0.05% formulation at a topical dose of 0.2 g cream/kg/day in rats and at a topical dose of 0.6 g cream/kg/day in rabbits. These doses (0.2 g cream/kg/day in rats and 0.6 g cream/kg/day in rabbits) are similar to the maximum recommended human dose based on body surface area comparisons.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Prenacid Foam is administered to a nursing woman.

If used during lactation, Prenacid Foam should not be applied on the chest to avoid accidental ingestion by the infant.

Pediatric Use

Safety and efficacy in pediatric patients younger than 3 months have not been established; therefore, the use of Prenacid Foam is not recommended.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and an 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 least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

The effect of Prenacid Foam on HPA axis function was investigated in pediatric subjects, aged 6 months to 17 years in one trial. In this trial, subjects with atopic dermatitis covering at least 25% of their body applied Prenacid Foam twice daily for 4 weeks. Three out of 75 subjects (4%) displayed adrenal suppression after 4 weeks of use based on the ACTH stimulation test. The suppression was transient; all subjects’ cortisol levels had returned to normal when tested 4 weeks post-treatment.

Geriatric Use

Clinical trials of Prenacid Foam did not include any subjects aged 65 or over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In a controlled clinical trial of 581 subjects aged 3 months to 17 years, adverse reactions occurred at the application site in 6% of subjects treated with Prenacid Foam and 14% of subjects treated with vehicle foam. Other commonly reported adverse reactions for Prenacid Foam and vehicle foam are noted in Table 1.

Table 1. Adverse Reactions in the Clinical Trial

Other local adverse events occurred at rates less than 1.0%. The majority of adverse reactions were transient and mild to moderate in severity, and they were not affected by age, race, or gender.

The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria.

Post-Marketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post-approval use of Prenacid Foam: application site irritation, application site erythema, application site reactions, skin reactions, and swelling face.

Topically applied Prenacid Foam can be absorbed in sufficient amounts to produce systemic effects.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids.

In an HPA axis suppression trial, three of 75 (4%) pediatric subjects with mild to moderate atopic dermatitis covering at least 25% body surface area, who applied Prenacid Foam twice daily, experienced reversible suppression of the adrenal glands (as indicated by a 30-minute post-stimulation cortisol level 18 mcg/dL) following 4 weeks of therapy..

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation, the integrity of the epidermal barrier, and age. Occlusion, inflammation, and/or other disease processes in the skin may also increase percutaneous absorption. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized primarily in the liver and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.