Included as part of the PRECAUTIONS section.
Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression And
Other Unwanted Systemic Glucocorticoid Effects
SERNIVO Spray can produce reversible
hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for
glucocorticosteroid insufficiency. This may occur during or after withdrawal of
treatment. Factors that predispose to HPA axis suppression include the use of high-potency
corticosteroids, 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.
In a study including 48 evaluable subjects 18 years of
age or older with moderate to severe plaque psoriasis, abnormal ACTH
stimulation test results suggestive of adrenal suppression were identified in 5
out of 24 (20.8%) subjects after treatment with SERNIVO Spray twice daily for 15
days . No subject (0 out of 24) had abnormal ACTH stimulation test results
after treatment with SERNIVO Spray twice daily for 29 days [see CLINICAL
If HPA axis suppression is documented, gradually withdraw
the drug, reduce the frequency of application, or substitute with a less potent
corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental
systemic corticosteroids may be required.
Systemic effects of topical corticosteroids may also
manifest as Cushing's syndrome, hyperglycemia, and glucosuria. These events are
rare and generally occur after prolonged exposure to larger than recommended
doses, particularly with high-potency topical corticosteroids.
Minimize the unwanted risks from endocrine effects by
mitigating the risk factors favoring increased systemic bioavailability and by
using the product as recommended [see DOSAGE AND ADMINISTRATION].
Pediatric patients may be more susceptible to systemic
toxicity due to their larger skin surface to body mass ratios. Use of SERNIVO
Spray is not recommended in pediatric patients [see Use In Specific
Use of topical corticosteroids, including SERNIVO Spray,
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 betamethasone dipropionate [see ADVERSE
Avoid contact of SERNIVO Spray with eyes. Advise patients
to report any visual symptoms and consider referral to an ophthalmologist for
Allergic Contact Dermatitis
Allergic contact dermatitis with corticosteroids is
usually diagnosed by observing failure to heal rather than noting a clinical
exacerbation. Corroborate such an observation with appropriate diagnostic patch
testing. If irritation develops, discontinue the topical corticosteroid and
institute appropriate therapy.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION and Instructions for Use).
Inform patients of the following:
- Discontinue therapy when control is achieved, unless
directed otherwise by the physician.
- Do not use for longer than 4 consecutive weeks.
- Avoid contact with the eyes.
- Avoid use of SERNIVO Spray on the face, scalp, underarms,
groin or other intertriginous areas, unless directed by the physician.
- Do not occlude the treatment area with bandage or other
covering, unless directed by the physician.
- Local reactions and skin atrophy are more likely to occur
with occlusive use, prolonged use, or use of higher potency corticosteroids.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term animal studies have not been performed to
evaluate the carcinogenic potential of betamethasone dipropionate.
In a 90-day repeat-dose toxicity study in rats, topical
administration of betamethasone dipropionate spray formulation at dose
concentrations of 0.05% and 0.1% (providing dose levels up to 0.5 mg/kg/day in
males and 0.25 mg/kg/day in females) resulted in a toxicity profile consistent
with long-term exposure to corticosteroids including reduced body weight gain, adrenal
atrophy, and histological changes in bone marrow, thymus and spleen indicative
of severe immune suppression. 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 of
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.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in
pregnant women. SERNIVO Spray 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
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 SERNIVO Spray is administered
to a nursing woman.
Safety and effectiveness of SERNIVO Spray in patients
younger than 18 years of age have not been studied; therefore use in pediatric
patients is not recommended. Because of a higher ratio of skin surface area to
body mass, pediatric patients are at greater risk of systemic toxicity, including
HPA axis suppression and adrenal insufficiency, when treated with topical
drugs. [see WARNINGS AND PRECAUTIONS]
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.
Clinical studies of SERNIVO Spray did not include
sufficient numbers of subjects who were 65 years of age or older to determine
whether they respond differently from younger subjects.