Included as part of the PRECAUTIONS section.
Effect on Endocrine System
Systemic absorption of topical corticosteroids, including Vanos Cream, can
produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with
the potential for clinical glucocorticosteroid insufficiency. This may occur
during treatment or upon withdrawal of the topical corticosteroid. In addition,
the use of VANOS Cream for longer than 2 weeks may suppress the immune system
[see Nonclinical Toxicology].
HPA axis suppression has been observed with VANOS Cream, 0.1% applied once
or twice daily in 2 out of 18 adult patients with plaque-type psoriasis, 1 out
of 31 adult patients with atopic dermatitis and 4 out of 123 pediatric patients
with atopic dermatitis [see Use in Specific Population and CLINICAL
Because of the potential for systemic absorption, use of topical corticosteroids, including Vanos Cream, may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.
An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal
insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.
Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.
Use of more than one corticosteroid-containing product at the same time may increase the total systemic absorption of topical corticosteroids.
Studies conducted in pediatric patients demonstrated reversible HPA axis suppression
after use of VANOS Cream. Pediatric patients may be more susceptible than adults
to systemic toxicity from equivalent doses of VANOS Cream due to their larger
skin surface-to-body-mass ratios [See Use In Specific Populations].
Local Adverse Reactions with Topical Corticosteroids
Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasis, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible.
Concomitant Skin Infections
If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of VANOS Cream should be discontinued until the infection has been adequately controlled.
Allergic Contact Dermatitis
If irritation develops, VANOS Cream should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.
Patient Counseling Information
[See FDA-approved patient labeling (PATIENT INFORMATION)]
Patients using VANOS Cream 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 unintended effects:
- VANOS Cream is to be used as directed by the physician. It is for external
use only. Avoid contact with the eyes. It should not be used on the face, groin, and underarms.
- VANOS Cream should not be used for any disorder other than that for which
it was prescribed.
- The treated skin area should not be bandaged or otherwise covered or wrapped,
so as to be occlusive unless directed by the physician.
- Patients should report to their physician any signs of local adverse reactions.
- Other corticosteroid-containing products should not be used with VANOS
Cream without first talking to the physician.
- As with other corticosteroids, therapy should be discontinued when control
is achieved. If no improvement is seen in 2 weeks, the patient should be instructed
to contact a physician. The safety of the use of VANOS Cream for longer than
2 weeks has not been established.
- Patients should be informed to not use more than 60 g per week of VANOS
Cream. Do not use more than half of the 120 g tube per week.
- Patients should inform their physicians that they are using VANOS Cream
if surgery is contemplated.
- Patients should wash their hands after applying medication.
Carcinogcncsis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential of VANOS Cream because of severe immunosuppression induced in a 13-week dermal rat study. The effects of fluocinonide on fertility have not been evaluated.
Fluocinonide revealed no evidence of mutagenic or clastogenic potential based
on the results of two in vitro genotoxicity tests (Ames test and chromosomal
aberration assay using human lymphocytes). However, fluocinonide was positive
for clastogenic potential when tested in the in vivo mouse micronucleus
Topical (dermal) application of 0.0003%-0.03% fluocinonide cream to rats once daily for 13 weeks resulted in a toxicity profile generally associated with long term exposure to corticosteroids including decreased skin thickness, adrenal atrophy, and severe immunosuppression. A NOAEL could not be determined in this study. In addition, topical (dermal) application of 0.1% fluocinonide cream plus UVR exposure to hairless mice for 13 weeks and 150-900 mg/kg/day of 0.1% fluocinonide cream to minipigs (a model which more closely approximates human skin) for 13 weeks produced glucocorticoid-related suppression of the HPA axis, with some signs of immunosuppression noted in the dermal minipig 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 for carcinogenesis.
Topical doses of 0% (fluocinonide cream vehicle), 0.0001%, 0.005% and 0.001% fluocinonide cream were evaluated in a 52 week dermal photo-carcinogenicity study (40 weeks of treatment followed by 12 weeks of observation) conducted in hairless albino mice with concurrent exposure to low level ultraviolet radiation. Topical treatment with increasing concentrations of fluocinonide cream did not have an adverse effect in this study. The results of this study suggest that topical treatment with VANOS Cream would not enhance photo-carcinogenesis.
Use In Specific Populations
Teratogenic Effects: Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Therefore, VANOS Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. 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.
Safety and efficacy of VANOS Cream in pediatric patients younger than 12 years of age have not been established; therefore use in pediatric patients younger than 12 years of age is not recommended.
HPA axis suppression was studied in 4 sequential cohorts of pediatric patients
with atopic dermatitis covering at least 20% of the body surface area, treated
once daily or twice daily with VANOS Cream. The first cohort of 31 patients
(mean 36.3% BSA) 12 to < 18 years old; the second cohort included 31 patients
(mean 39.0% BSA) 6 to < 12 years old; the third cohort included 30 patients
(mean 34.6% BSA) 2 to < 6 years old; the fourth cohort included 31 patients
(mean 40.0% BSA) 3 months to < 2 years old. VANOS Cream caused HPA-axis suppression
in 1 patient in the twice daily group in Cohort 1, 2 patients in the twice daily
group in Cohort 2, and 1 patient in the twice daily group in Cohort 3. Follow-up
testing 14 days after treatment discontinuation, available for all 4 suppressed
patients, demonstrated a normally responsive HPA axis. Signs of skin atrophy
were present at baseline and severity was not determined making it difficult
to assess local skin safety. Therefore, the safety of VANOS Cream in patients
younger than 12 years of age has not been demonstrated [see WARNINGS
HPA axis suppression has not been evaluated in patients with psoriasis who are less than 18 years of age.
Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA-axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.
HPA-axis suppression, Cushing's syndrome, linear growth retardation, delayed
weight gain, and intracranial hypertension have been reported in children receiving
topical corticosteroids. Manifestations of adrenal suppression in children include
low plasma cortisol levels and absence of response to cosyntropin (ACTH1-24)
stimulation. Manifestations of intracranial hypertension include bulging fontanelles,
headaches, and bilateral papilledema.
Clinical studies of VANOS Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.