NDC 0085-0517 Diprolene Af

Betamethasone Dipropionate

NDC Product Code 0085-0517

NDC 0085-0517-01

Package Description: 1 TUBE in 1 BOX > 15 g in 1 TUBE

NDC 0085-0517-04

Package Description: 1 TUBE in 1 BOX > 50 g in 1 TUBE

NDC Product Information

Diprolene Af with NDC 0085-0517 is a a human prescription drug product labeled by Merck Sharp & Dohme Corp.. The generic name of Diprolene Af is betamethasone dipropionate. The product's dosage form is cream and is administered via topical form.

Labeler Name: Merck Sharp & Dohme Corp.

Dosage Form: Cream - An emulsion, semisolid3 dosage form, usually containing > 20% water and volatiles5 and/or < 50% hydrocarbons, waxes, or polyols as the vehicle. This dosage form is generally for external application to the skin or mucous membranes.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Diprolene Af Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • BETAMETHASONE DIPROPIONATE .5 mg/g

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • WATER (UNII: 059QF0KO0R)
  • CHLOROCRESOL (UNII: 36W53O7109)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • PETROLATUM (UNII: 4T6H12BN9U)
  • WHITE WAX (UNII: 7G1J5DA97F)
  • CYCLOMETHICONE (UNII: NMQ347994Z)
  • SORBITOL (UNII: 506T60A25R)
  • GLYCERYL OLEATE (UNII: 4PC054V79P)
  • CETEARETH-30 (UNII: 1R9DCZ5FOX)
  • CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Topical - Administration to a particular spot on the outer surface of the body. The E2B term TRANSMAMMARY is a subset of the term TOPICAL.
  • Topical - Administration to a particular spot on the outer surface of the body. The E2B term TRANSMAMMARY is a subset of the term TOPICAL.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Corticosteroid - [EPC] (Established Pharmacologic Class)
  • Corticosteroid Hormone Receptor Agonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Merck Sharp & Dohme Corp.
Labeler Code: 0085
FDA Application Number: NDA019555 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 04-27-1987 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Information for Patients

Betamethasone Topical

Betamethasone Topical is pronounced as (bay ta meth' a sone)

Why is betamethasone topical medication prescribed?
Betamethasone is used to treat the itching, redness, dryness, crusting, scaling, inflammation, and discomfort of various skin conditions.This medication is sometimes pres...
[Read More]

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Diprolene Af Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

DIPROLENE® AF Cream is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age or older.

2 Dosage And Administration

Apply a thin film of DIPROLENE AF Cream to the affected skin areas once or twice daily.Therapy should be discontinued when control is achieved. DIPROLENE AF Cream is a high-potency corticosteroid. Treatment with DIPROLENE AF Cream should not exceed 50 g per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis [see Warnings and Precautions (5.1)].DIPROLENE AF Cream should not be used with occlusive dressings unless directed by a physician.Avoid contact with eyes. Wash hands after each application. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site.DIPROLENE AF Cream is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

3 Dosage Forms And Strengths

Cream, 0.05%. Each gram of DIPROLENE AF Cream, 0.05% contains 0.643 mg betamethasone dipropionate (equivalent to 0.5 mg betamethasone) in a white cream base.

4 Contraindications

DIPROLENE AF Cream 0.05% is contraindicated in patients who are hypersensitive to betamethasone dipropionate, to other corticosteroids, or to any ingredient in this preparation.

5.1 Effects On Endocrine System

DIPROLENE AF Cream can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test. DIPROLENE AF Cream 0.05% was applied once daily at 7 grams per day for 1 week to diseased skin, in adult subjects with psoriasis or atopic dermatitis, to study its effects on the HPA axis. The results suggested that the drug lowered adrenal corticosteroid secretion, although plasma cortisol levels did not go below the lower limit of the normal range.In an open-label pediatric trial of 60 evaluable subjects (3 months to 12 years of age), 19 subjects showed evidence of HPA axis suppression. Four (4) subjects were tested 2 weeks after discontinuation of DIPROLENE AF Cream 0.05%, and 3 of the 4 (75%) had complete recovery of HPA axis function. The proportion of subjects with adrenal suppression in this trial was progressively greater, the younger the age group.If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Cushing's syndrome and hyperglycemia may also occur with topical corticosteroids. These events are rare and generally occur after prolonged exposure to excessively large doses, especially of high-potency topical corticosteroids.Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios [see Use in Specific Populations (8.4)].

5.2 Visual Disturbance

Use of topical corticosteroids, including DIPROLENE AF Cream, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing with the use of topical corticosteroid products, including DIPROLENE AF Cream [see Adverse Reactions (6.2)].Avoid contact of DIPROLENE AF Cream with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

5.3 Allergic Contact Dermatitis

Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing. If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.

6.1 Clinical Trials 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 controlled clinical trials, involving 242 adult subjects, the adverse reaction associated with the use of DIPROLENE AF Cream reported at a frequency of 0.4% was stinging. It occurred in 1 subject. In a controlled clinical trial involving 67 pediatric subjects from 3 months to 12 years of age, the adverse reactions associated with the use of DIPROLENE AF Cream occurred in 7 of 67 (10%) subjects. Reported reactions included signs of skin atrophy (telangiectasia, bruising, shininess).

6.2 Postmarketing Experience

Because adverse 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.Postmarketing reports for local adverse reactions to topical corticosteroids may also include: burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, skin atrophy, striae, and miliaria.Hypersensitivity reactions, consisting of predominantly skin signs and symptoms, e.g., contact dermatitis, pruritus, bullous dermatitis, and erythematous rash have been reported.Ophthalmic adverse reactions of cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported with the use of topical corticosteroids, including topical betamethasone products.

Teratogenic Effects

Teratogenic Effects: Pregnancy Category CThere are no adequate and well-controlled studies in pregnant women. DIPROLENE AF Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Betamethasone dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias, cephalocele, and cleft palate.

8.3 Nursing Mothers

Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids can 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 DIPROLENE AF Cream is administered to a nursing woman.

8.4 Pediatric Use

Use of DIPROLENE AF Cream in pediatric patients younger than 13 years of age is not recommended due to the potential for HPA axis suppression [see Warnings and Precautions (5.1)]. In an open-label HPA axis safety trial in subjects 3 months to 12 years of age with atopic dermatitis, DIPROLENE AF Cream 0.05% was applied twice daily for 2 to 3 weeks over a mean body surface area of 58% (range 35% to 95%). In 19 of 60 (32%) evaluable subjects, adrenal suppression was indicated by either a ≤5 mcg/dL pre-stimulation cortisol, or a cosyntropin post-stimulation cortisol ≤18 mcg/dL and/or an increase of <7 mcg/dL from the baseline cortisol. Out of the 19 subjects with HPA axis suppression, 4 subjects were tested 2 weeks after discontinuation of DIPROLENE AF Cream, and 3 of the 4 (75%) had complete recovery of HPA axis function. The proportion of subjects with adrenal suppression in this trial was progressively greater, the younger the age group [see Warnings and Precautions (5.1)].Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity when treated with topical drugs. They are, therefore, also at greater risk of HPA axis suppression and adrenal insufficiency upon the use of topical corticosteroids.Rare systemic effects such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids.Local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients.Avoid use of DIPROLENE AF Cream in the treatment of diaper dermatitis.

8.5 Geriatric Use

Clinical trials of DIPROLENE AF Cream included 104 subjects who were 65 years of age and over and 8 subjects who were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. However, greater sensitivity of some older individuals cannot be ruled out.

11 Description

DIPROLENE AF (augmented betamethasone dipropionate) Cream 0.05% contains betamethasone dipropionate USP, a synthetic adrenocorticosteroid, for topical use in a cream base. Betamethasone, an analog of prednisolone, has a high degree of corticosteroid activity and a slight degree of mineralocorticoid activity. Betamethasone dipropionate is the 17,21-dipropionate ester of betamethasone.Chemically, betamethasone dipropionate is 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate, with the empirical formula C28H37FO7, a molecular weight of 504.6, and the following structural formula:Betamethasone dipropionate is a white to creamy white, odorless crystalline powder, insoluble in water.Each gram of DIPROLENE AF Cream 0.05% contains: 0.643 mg betamethasone dipropionate USP (equivalent to 0.5 mg betamethasone) in a white cream base of carbomer 940; ceteareth-30; chlorocresol; cyclomethicone; glyceryl oleate/propylene glycol; propylene glycol; purified water; sodium hydroxide; sorbitol solution; white petrolatum; and white wax.

12.1 Mechanism Of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of DIPROLENE AF Cream in corticosteroid responsive dermatoses is unknown.

12.3 Pharmacokinetics

No pharmacokinetics trials have been conducted with DIPROLENE AF Cream 0.05%. The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings [see Dosage and Administration (2)].Topical corticosteroids can be absorbed through normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids [see Dosage and Administration (2)].Once absorbed through the skin, topical corticosteroids enter pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees, are metabolized primarily in the liver, and excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of betamethasone dipropionate.Betamethasone was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in vitro human lymphocyte chromosome aberration assay, and equivocal in the in vivo mouse bone marrow micronucleus assay.Studies in rabbits, mice, and rats using intramuscular doses up to 1, 33, and 2 mg/kg, respectively, resulted in dose-related increases in fetal resorptions in rabbits and mice.

14 Clinical Studies

The safety and efficacy of DIPROLENE AF Cream for the treatment of corticosteroid-responsive dermatoses have been established in two randomized and active controlled trials in subjects with chronic plaque psoriasis. A total of 81 subjects who received DIPROLENE AF Cream were included in these trials. These trials evaluated DIPROLENE AF Cream applied once or twice daily for 14 and 21 days, respectively, on bilateral paired psoriatic lesions. DIPROLENE AF Cream was shown to be effective in relieving the signs and symptoms of chronic plaque psoriasis.

16 How Supplied/Storage And Handling

DIPROLENE AF Cream 0.05% is a white cream supplied in 15-g (NDC 0085-0517-01) and 50-g (NDC 0085-0517-04) tubes.

Storage And Handling

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

17 Patient Counseling Information

  • Inform patients of the following:Discontinue therapy when control is achieved, unless directed otherwise by the physician. Use no more than 50 grams per week.Avoid contact with the eyes.Advise patients to report any visual symptoms to their healthcare providers.Avoid use of DIPROLENE AF Cream on the face, underarms, or groin areas unless directed by the physician.Do not occlude the treatment area with bandage or other covering, unless directed by the physician.Note that local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids.

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