Betamethasone Dipropionate (Page 2 of 3)

8.2 Lactation

Risk Summary
There are no data regarding the presence of betamethasone dipropionate in human milk, the effects on the breastfed infant or the effects on milk production after topical application Betamethasone Dipropionate Ointment to women who are breastfeeding.
It is possible that topical administration of betamethasone dipropionate could result in sufficient systemic absorption to product detectable quantities in human milk. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Betamethasone Dipropionate Ointment and any potential adverse effects on the breastfed infant from Betamethasone Dipropionate Ointment or from the underlying maternal condition.
Clinical Considerations
To minimize potential exposure to the breastfed infant via breast milk, use Betamethasone Dipropionate Ointment on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Betamethasone Dipropionate Ointment directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.4) ].

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 Betamethasone Dipropionate Ointment is administered to a nursing woman.

8.4 Pediatric Use

Use of Betamethasone Dipropionate Ointment 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, Betamethasone Dipropionate 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 Betamethasone Dipropionate 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.

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 Betamethasone Dipropionate Ointment in the treatment of diaper dermatitis.

8.5 Geriatric Use

Clinical trials of Betamethasone Dipropionate Ointment included 225 subjects who were 65 years of age and over and 46 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

Betamethasone Dipropionate Ointment USP, 0.05% (Augmented) contains betamethasone dipropionate USP, a synthetic adrenocorticosteroid, for topical use. 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 C28 H37 FO7 , a molecular weight of 504.6 and the following structural formula:

structural formula

It is a white to creamy-white, odorless powder insoluble in water; freely soluble in acetone and in chloroform; sparingly soluble in alcohol.

Each gram of Betamethasone Dipropionate Ointment USP, 0.05% contains 0.643 mg betamethasone dipropionate USP (equivalent to 0.5 mg betamethasone), in a white ointment base of propylene glycol; propylene glycol stearate; white petrolatum; and white wax.

12 CLINICAL PHARMACOLOGY

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 Betamethasone Dipropionate Ointment in corticosteroid responsive dermatoses is unknown.

12.2 Pharmacodynamics

Vasoconstrictor Assay

Trials performed with Betamethasone Dipropionate Ointment, 0.05% indicate that it is in the super-high range of potency as demonstrated in vasoconstrictor trials in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

12.3 Pharmacokinetics

No pharmacokinetics trials have been conducted with Betamethasone Dipropionate Ointment.

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.

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 NONCLINICAL TOXICOLOGY

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 Betamethasone Dipropionate Ointment for the treatment of corticosteroid-responsive dermatoses, psoriasis and atopic dermatitis, have been evaluated in three randomized active-controlled trials, two in psoriasis and one in atopic dermatitis. A total of 378 subjects, of whom 152 received Betamethasone Dipropionate Ointment, were included in these trials. These trials evaluated Betamethasone Dipropionate Ointment applied twice daily, for 14 days. Betamethasone Dipropionate Ointment was shown to be effective in relieving signs and symptoms of psoriasis and atopic dermatitis.

16 HOW SUPPLIED/STORAGE AND HANDLING

Betamethasone Dipropionate Ointment USP, 0.05% (Augmented) is a white ointment supplied in the following tube sizes:
15 g tube (NDC 52565-019-15)
50 g tube (NDC52565-019-51)

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

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.