HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
DIPROLENE Ointment safely and effectively. See full prescribing
information for DIPROLENE Ointment.
DIPROLENE® (augmented betamethasone dipropionate) ointment,
for topical use
Initial U.S. Approval: 1983----------------------------INDICATIONS AND USAGE ---------------------------DIPROLENE Ointment is a corticosteroid indicated for the relief of theinflammatory and pruritic manifestations of corticosteroid-responsive
dermatoses in patients 13 years of age and older. (1)----------------------- DOSAGE AND ADMINISTRATION ----------------------•
Apply a thin film to the affected skin areas once or twice daily. (2)•Discontinue therapy when control is achieved. (2)•Limit therapy to no more than 2 consecutive weeks. (2)•Use no more than 50 g per week. (2)•Do not use with occlusive dressings unless directed by aphysician. (2)•Avoid use on the face, groin, or axillae, or if skin atrophy ispresent at the treatment site. (2)•Not for oral, ophthalmic, or intravaginal use. (2)--------------------- DOSAGE FORMS AND STRENGTHS --------------------•Ointment, 0.05% (3)•Hypersensitivity to any component of this medicine. (4)----------------------- WARNINGS AND PRECAUTIONS ----------------------•
Effects on endocrine system: DIPROLENE Ointment can cause
reversible HPA axis suppression with the potential for
glucocorticosteroid insufficiency during and after withdrawal oftreatment. Risk factor(s) include the use of high-potency topicalcorticosteroids, use over a large surface area or to areas underocclusion, prolonged use, altered skin barrier, liver failure, and use
in pediatric patients. Modify use should HPA axis suppression
develop. (5.1, 8.4)
•Ophthalmic Adverse Reactions: DIPROLENE Ointment may
increase the risk of cataracts and glaucoma. If visual symptoms
occur, consider referral to an ophthalmologist for evaluation. (5.2)------------------------------ ADVERSE REACTIONS -----------------------------Most common adverse reactions (<1%) are: erythema, folliculitis,
pruritus, and vesiculation. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Organon
LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling.
Revised: 2/2022-------------------------------CONTRAINDICATIONS ------------------------------FULL PRESCRIBING INFORMATION: CONTENTS*1234568INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATIONDOSAGE FORMS AND STRENGTHSCONTRAINDICATIONSWARNINGS AND PRECAUTIONS
5.1 Effects on Endocrine System
5.2 Ophthalmic Adverse Reactions
5.3 Allergic Contact Dermatitis
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation

111213141617

8.4 Pediatric Use
8.5 Geriatric Use
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIESHOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information
are not listed.

FULL PRESCRIBING INFORMATION
1

INDICATIONS AND USAGE

DIPROLENE® Ointment 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 Ointment to the affected skin areas once or twice daily.
Therapy should be discontinued when control is achieved. If no improvement is seen within 2weeks, reassessment of diagnosis may be necessary. DIPROLENE Ointment is a super-high-potency
topical corticosteroid. Treatment with DIPROLENE Ointment should not exceed 50 g per week becauseof the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis [see Warnings andPrecautions (5.1)].
DIPROLENE Ointment should not be used with occlusive dressings unless directed by a physician.
Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site.
Avoid contact with eyes. Wash hands after each application.
DIPROLENE Ointment is for topical use only. It is not for oral, ophthalmic, or intravaginal use.
3DOSAGE FORMS AND STRENGTHSOintment, 0.05%. Each gram of DIPROLENE Ointment, 0.05% contains 0.643 mg betamethasone
dipropionate (equivalent to 0.5 mg betamethasone) in a white to off-white ointment base.
4CONTRAINDICATIONSDIPROLENE Ointment is contraindicated in patients who are hypersensitive to betamethasone
dipropionate, to other corticosteroids, or to any ingredient in this preparation.
5WARNINGS AND PRECAUTIONS

5.1

Effects on Endocrine System
DIPROLENE Ointment can produce reversible hypothalamic-pituitary-adrenal (HPA) axis
suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment orafter withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of highpotency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skinbarrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using theadrenocorticotropic hormone (ACTH) stimulation test.
In a trial evaluating the effects of DIPROLENE Ointment on the HPA axis, at 14 g per day,
DIPROLENE Ointment was shown to suppress the plasma levels of adrenal cortical hormones following
repeated application to diseased skin in subjects with psoriasis. These effects were reversible upon
discontinuation of treatment. At 7 g per day, DIPROLENE Ointment was shown to cause minimal
inhibition of the HPA axis when applied 2 times daily for 2 to 3 weeks in healthy subjects and in subjects
with psoriasis and eczematous disorders.
With 6 g to 7 g of DIPROLENE Ointment applied once daily for 3 weeks, no significant inhibition of
the HPA axis was observed in subjects with psoriasis and atopic dermatitis, as measured by plasma
cortisol and 24-hour urinary 17-hydroxy-corticosteroid levels.
If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency ofapplication, 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 highpotency topical corticosteroids.
Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface tobody mass ratios [see Use in Specific Populations (8.4)].

2

5.2

Ophthalmic Adverse Reactions
Use of topical corticosteroids, including DIPROLENE Ointment, may increase the risk of posterior
subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing withthe use of topical corticosteroid products, including DIPROLENE Ointment [see Adverse Reactions (6.2)].
Avoid contact of DIPROLENE Ointment 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 andappropriate therapy instituted.
6ADVERSE REACTIONS

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 anotherdrug and may not reflect the rates observed in clinical practice.
In controlled clinical trials, adverse reactions associated with the use of DIPROLENE Ointment
reported at a frequency of less than 1% included erythema, folliculitis, pruritus, and vesiculation.
6.2

Postmarketing Experience
Because adverse reactions are reported voluntarily from a population of uncertain size, it is notalways 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: skin
atrophy, telangiectasias, burning, irritation, dryness, acneiform eruptions, hypopigmentation, perioraldermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, 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 topicalbetamethasone products.
8USE IN SPECIFIC POPULATIONS

8.1

Pregnancy
Risk Summary
There are no available data on DIPROLENE Ointment use in pregnant women to identify a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Observational studies suggest an increased risk of low birthweight infants with the use of greaterthan 300 grams of potent or very potent topical corticosteroid during a pregnancy. Advise pregnant
women that DIPROLENE Ointment may increase the risk of having a low birthweight infant and to use
DIPROLENE Ointment on the smallest area of skin and for the shortest duration possible.
In animal reproduction studies, increased malformations, including umbilical hernias, cephalocele,and cleft palate, were observed after intramuscular administration of betamethasone dipropionate topregnant rabbits. The available data do not allow the calculation of relevant comparisons between thesystemic exposure of betamethasone dipropionate in animal studies to the systemic exposure that would
be expected in humans after topical use of DIPROLENE Ointment (see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated risk of major birth defects and miscarriage in clinically recognizedpregnancies is 2 to 4% and 15 to 20%, respectively.

3

Data
Animal Data
Betamethasone dipropionate has been shown to cause malformations in rabbits when given by theintramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias,cephalocele, and cleft palate.
8.2

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

Pediatric Use
Use of DIPROLENE Ointment in pediatric patients younger than 13 years of age is notrecommended 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 byeither 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, 4subjects 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.
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 ofHPA 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 topicalcorticosteroids in pediatric patients.
Avoid use of DIPROLENE Ointment in the treatment of diaper dermatitis.
8.5

Geriatric Use
Clinical trials of DIPROLENE Ointment included 225 subjects who were 65 years of age and overand 46 subjects who were 75 years of age and over. No overall differences in safety or effectivenesswere 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.
11DESCRIPTIONDIPROLENE (augmented betamethasone dipropionate) Ointment, 0.05% contains betamethasone
dipropionate USP, a synthetic adrenocorticosteroid, for topical use. Betamethasone, an analog ofprednisolone, has a high degree of corticosteroid activity and a slight degree of mineralocorticoid activity.
Betamethasone dipropionate is the 17, 21-dipropionate ester of betamethasone.
4Chemically,
betamethasone
dipropionateis9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate, with the empirical formula C28H37FO7, amolecular weight of 504.6 and the following structural formula:

It is a white to creamy-white, odorless powder insoluble in water; freely soluble in acetone and inchloroform; sparingly soluble in alcohol.
Each gram of DIPROLENE Ointment, 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.
12CLINICAL 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 DIPROLENE Ointment in corticosteroid
responsive dermatoses is unknown.
12.2 Pharmacodynamics
Vasoconstrictor Assay
Trials performed with DIPROLENE Ointment, 0.05% indicate that it is in the super-high range ofpotency as demonstrated in vasoconstrictor trials in healthy subjects when compared with other topicalcorticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.
12.3 Pharmacokinetics
No pharmacokinetics trials have been conducted with DIPROLENE 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 otherdisease 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 tosystemically 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 topicalcorticosteroids and their metabolites are also excreted into the bile.
13NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential ofbetamethasone dipropionate.
Betamethasone was negative in the bacterial mutagenicity assay (Salmonella typhimurium andEscherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the invitro 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.

5

14

CLINICAL STUDIESThe safety and efficacy of DIPROLENE 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
DIPROLENE Ointment, were included in these trials. These trials evaluated DIPROLENE Ointment
applied twice daily, for 14 days. DIPROLENE Ointment was shown to be effective in relieving signs andsymptoms of psoriasis and atopic dermatitis.
16

HOW SUPPLIED/STORAGE AND HANDLINGDIPROLENE Ointment 0.05% is a white ointment supplied in 15-g (NDC 78206-124-01) and 50-g
(NDC 78206-124-02) tubes.
Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP Controlled RoomTemperature].
17PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient 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 of DIPROLENE Ointment and no longer than 2
consecutive weeks.
• Avoid contact with the eyes.
• Advise patients to report any visual symptoms to their healthcare providers.
• Avoid use of DIPROLENE Ointment on the face, underarms, or groin areas unless directed bythe physician.
• Do not occlude the treatment area with bandage or other covering, unless directed by thephysician.
• Note that local reactions and skin atrophy are more likely to occur with occlusive use, prolonged
use or use of higher potency corticosteroids.
• Advise a woman to use DIPROLENE Ointment on the smallest area of skin and for the shortest
duration possible while pregnant or breastfeeding. Advise breastfeeding women not to apply
DIPROLENE Ointment directly to the nipple and areola to avoid direct infant exposure.

For patent information: www.organon.com/our-solutions/patent/© 2022 Organon group of companies. All rights reserved.
uspi-og1460-ot-2202r001

6