DIPROLENE® AF Cream 0.05% contains betamethasone dipropionate, USP, a synthetic adrenocorticosteroid, for dermatologic use in an emollient 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 an emollient cream base of purified water, USP; chlorocresol; propylene glycol, USP; white petrolatum, USP; white wax, NF; cyclomethicone; sorbitol solution, USP; glyceryl oleate/propylene glycol; ceteareth-30; carbomer 940, NF; and sodium hydroxide R.

Last updated on RxList: 10/14/2008

DIPROLENE AF Cream 0.05% is a high-potency corticosteroid indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years and older.

Apply a thin film of DIPROLENE AF Cream 0.05% to the affected skin areas once or twice daily. Treatment with DIPROLENE AF Cream 0.05% should be limited to 45 g per week.

DIPROLENE AF Cream 0.05% is not to be used with occlusive dressings.

DIPROLENE AF Cream 0.05% is supplied in 15-g (NDC 0085-0517-01) and 50-g (NDC 0085-0517-04) tubes; boxes of one.

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

Schering Corporation, Kenilworth, NJ 07033, USA. Rev. 10/05. FDA Rev date: 8/28/2006

Last updated on RxList: 10/14/2008

The only local adverse reaction reported to be possibly or probably related to treatment with DIPROLENE AF Cream 0.05% during adult controlled clinical studies was stinging. It occurred in 1 patient, 0.4%, of the 242 patients or subjects involved in the studies.

Adverse reactions reported to be possibly or probably related to treatment with DIPROLENE AF Cream 0.05% during a pediatric clinical study include signs of skin atrophy (telangiectasia, bruising, shininess). Skin atrophy occurred in 7 of 67 (10%) patients, involving all age groups from 3 months – 12 years of age.

The following local adverse reactions are reported infrequently when topical corticosteroids are used as recommended. These reactions dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

No information provided.

Last updated on RxList: 10/14/2008

No information provided.

General

Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

Conditions which augment systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure. (See DOSAGE AND ADMINISTRATION section.)

Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation 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 steroid.

Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. In an open-label pediatric study of 60 evaluable patients, of the 19 who showed evidence of suppression 4 patients 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. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids.

Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. (See PRECAUTIONS - Pediatric Use.)

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

In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

Laboratory Tests

The following tests may be helpful in evaluating HPA axis suppression:

Urinary free cortisol test
ACTH stimulation test

Carcinogenesis, Mutagenesis, and 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. This pattern of response is similar to that of dexamethasone and hydrocortisone.

Reproductive studies with betamethasone dipropionate carried out in rabbits at doses of 1.0 mg/kg by the intramuscular route and in mice up to 33 mg/kg by the intramuscular route indicated no impairment of fertility except for dose-related increases in fetal resorption rates in both species. These doses are approximately 5- and 38-fold the human dose based on a mg/m² comparison, respectively.

Pregnancy

Teratogenic Effects: Pregnancy Category C

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels.

Betamethasone dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. This dose is approximately 0.2- fold the maximum human dose based on a mg/m² comparison. The abnormalities observed included umbilical hernias, cephalocele and cleft palates.

Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

Nursing Mothers

It is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. Nevertheless, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Use of DIPROLENE AF Cream 0.05% in pediatric patients 12 years of age and younger is not recommended. (See CLINICAL PHARMACOLOGY and ADVERSE REACTIONS sections.) In an open-label study, 19 of 60 (32%) evaluable pediatric patients (aged 3 months-12 years old) using DIPROLENE AF Cream 0.05% for treatment of atopic dermatitis demonstrated HPA axis suppression. The proportion of patients with adrenal suppression in this study was progressively greater, the younger the age group. (See CLINICAL PHARMACOLOGY - Pharmacokinetics.)

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio. The study described above supports this premise, as adrenal suppression in 9-12 year olds, 6-8 year olds, 2-5 year olds, and 3 months-1 year old was 17%, 32%, 38% and 50% respectively.

Hypothalamic-pituitary-adrenal (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. Chronic corticosteroid therapy may interfere with the growth and development of children.

Geriatric Use

Clinical studies of DIPROLENE AF Cream 0.05% 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.

Last updated on RxList: 10/14/2008

Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)

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.

Last updated on RxList: 10/14/2008

The corticosteroids are a class of compounds comprising steroid hormones secreted by the adrenal cortex and their synthetic analogs. In pharmacologic doses, corticosteroids are used primarily for their anti-inflammatory and/or immunosuppressive effects.

Topical corticosteroids, such as betamethasone dipropionate, are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, antipruritic, and vasoconstrictive actions. However, while the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in each disease are uncertain. Betamethasone dipropionate, a corticosteroid, has been shown to have topical (dermatologic) and systemic pharmacologic and metabolic effects characteristic of this class of drugs.

Pharmacokinetics

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 section.)

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 section.)

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.

DIPROLENE AF Cream 0.05% was applied once daily at 7 grams per day for 1 week to diseased skin, in adult patients with psoriasis or atopic dermatitis, to study its effects on the hypothalamic-pituitary-adrenal (HPA) axis. The results suggested that the drug caused a slight lowering of adrenal corticosteroid secretion, although in no case did plasma cortisol levels go below the lower limit of the normal range.

Sixty-seven pediatric patients ages 1 to 12 years, with atopic dermatitis, were enrolled in an open-label, hypothalamic-pituitary-adrenal (HPA) axis safety study. 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 patients, adrenal suppression was indicated by either a ≥ 5 mcg/dL pre-stimulation cortisol, or a cosyntropin post-stimulation cortisol ≥ 8 mcg/dL and/or an increase of < 7 mcg/dL from the baseline cortisol. Studies performed with DIPROLENE AF Cream 0.05% indicate that it is in the high range of potency as compared with other topical corticosteroids.

Last updated on RxList: 10/14/2008

Patients using topical corticosteroids should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

1. This medication is to be used as directed by the physician and should not be used longer than the prescribed time period. It is for external use only. Avoid contact with the eyes.
2. Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive. (See DOSAGE AND ADMINISTRATION section.)
4. Patients should report any signs of local adverse reactions.
5. Other corticosteroid-containing products should not be used with DIPROLENE AF Cream 0.05% without first talking to your physician.

Last updated on RxList: 10/14/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BETAMETHASONE DIPROPIONATE AUGMENTED - TOPICAL

(bay-ta-METH-a-sone)

COMMON BRAND NAME(S): Diprolene

USES: This medication is used to treat a variety of skin conditions (e.g., eczema, dermatitis, allergies, rash). Betamethasone reduces the swelling, itching, and redness that can occur in these types of conditions. This medication is a strong to very strong (high- to super-high-potency) corticosteroid. The strength depends on the form (cream, gel, or ointment) that you use. For details on the strength of your product, ask your pharmacist.

HOW TO USE: Use this medication on the skin only. However, do not use it on the face, groin, or underarms or for diaper rash unless directed to do so by your doctor.

Wash and dry your hands. Before applying the medication, clean and dry the affected area. Apply a thin film of the medication to the affected area and gently rub in, usually 1-2 times daily or as directed by your doctor. Do not cover, bandage, or wrap the area. If your doctor directs you to use this medication in the diaper area on an infant, do not use tight-fitting diapers or plastic pants.

After applying the medication, wash your hands unless you are using this medication to treat the hands. When applying this medication near the eyes, avoid getting it in the eyes as this may worsen or cause glaucoma. Also, avoid getting this medication in the nose or mouth. If you get the medication in these areas, rinse with plenty of water.

Use this medication only for the condition prescribed. Do not use it for longer than 2 weeks in a row or use more than 50 grams of the gel or more than 45 grams of the cream/ointment per week unless directed to do so by your doctor.

Inform your doctor if your condition persists or worsens after 2 weeks.

SIDE EFFECTS: Burning, itching, irritation, or dryness at the application site may occur when this medication is first applied to the skin. This should disappear in a few days as your body adjusts to the medication. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor promptly if any of these unlikely but serious side effects occur: stretch marks, skin thinning/discoloration, acne, extreme/unwanted hair growth, "hair bumps" (folliculitis).

Skin infections can become worse when this medication is used. Notify your doctor if redness, swelling, or irritation does not improve.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using betamethasone, tell your doctor or pharmacist if you are allergic to it; or to other corticosteroids (e.g., hydrocortisone, prednisone); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: poor blood circulation, immune system problems, certain skin conditions if using the gel (rosacea, perioral dermatitis).

Do not use if there is an infection or sore present in the area to be treated.

Though very unlikely, it is possible this medication will be absorbed into your bloodstream. This may have undesirable consequences that may require additional corticosteroid treatment. This is especially true for children, those who have used this drug for an extended time, and those who have serious medical problems such as serious infections, injuries, or surgeries. This precaution applies for up to one year after you stop using this drug.

Tell your doctor immediately if any of the following side effects occur: vision problems, persistent headache, increased thirst/urination, unusual weight loss, unusual weakness, dizziness.

Consult your doctor or pharmacist for more details and inform them that you use or have used this medication.

Caution is advised when using this drug in children because they may be more sensitive to the effects of too much steroid hormone. Though it is unlikely to occur with corticosteroids applied to the skin, this medication may affect growth in infants and children if used for prolonged periods. Monitor your child's height and rate of growth periodically.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk when applied to the skin. Similar medications pass into breast milk when taken by mouth. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: corticosteroids taken by mouth (e.g., prednisone), drugs that lower the immune system (e.g., cyclosporine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for other skin problems unless told to do so by your doctor. A different medication may be necessary in those cases.

Laboratory and/or medical tests (e.g., adrenal gland function tests, morning cortisol blood test) may be performed periodically to monitor your progress or check for side effects if you use this drug for 2 weeks or longer, apply it over large areas of the body, or bandage/wrap the treated areas. Consult your doctor for more details.

Inform all your doctors that you use or have used this medication.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from heat and light. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.