Tepsim

Indication

La crème VANOS (fluocinonide), 0,1%, est indiquée pour le soulagement des manifestations inflammatoires et prurigineuses des dermatoses sensibles aux corticostéroïdes chez les patients de 12 ans ou plus.

Limitation d'utilisation

Le traitement au-delà de 2 semaines consécutives n'est pas recommandé et la posologie totale ne doit pas dépasser 60 g par semaine car la sécurité de la crème VANOS pendant plus de 2 semaines n'a pas été établie et en raison du potentiel du médicament à supprimer l'hypothalamic-hypophyse-adrénal (HPA). Le traitement doit être interrompu lorsque le contrôle de la maladie est atteint. Si aucune amélioration n'est observée dans les 2 semaines, une réévaluation du diagnostic peut être nécessaire. N'utilisez pas plus de la moitié du tube de 120 g par semaine.

La crème VANOS ne doit pas être utilisée dans le traitement de la rosacée ou de la dermatite périorale et ne doit pas être utilisée sur le visage, l'aine ou les axilles.

La crème Tepsim (fluocinonide) est indiquée pour le soulagement des manifestations inflammatoires et prurigineuses des dermatoses sensibles aux corticostéroïdes.

Pour usage topique uniquement. La crème VANOS n'est pas destinée à un usage ophtalmique, oral ou intravaginal.

Pour le psoriasis, appliquez une fine couche de crème VANOS une ou deux fois par jour sur les zones cutanées affectées selon les directives d'un médecin. Il a été démontré que deux fois l'application quotidienne du traitement du psoriasis est plus efficace pour réussir le traitement pendant 2 semaines de traitement.

Pour la dermatite atopique, appliquez une fine couche de crème VANOS une fois par jour sur les zones cutanées affectées selon les directives d'un médecin. Une fois par jour, l'application du traitement de la dermatite atopique s'est avérée aussi efficace qu'un traitement deux fois par jour pour réussir le traitement pendant 2 semaines de traitement.

Pour les dermatoses sensibles aux corticostéroïdes, autres que le psoriasis ou la dermatite atopique, appliquez une fine couche de crème VANOS une ou deux fois par jour sur les zones affectées selon les directives d'un médecin.

La crème Tepsim (fluocinonide) est généralement appliquée sur la zone affectée sous forme de film mince de deux à quatre fois par jour en fonction de la gravité de la maladie.

Des pansements occlusifs peuvent être utilisés pour la gestion du psoriasis ou des conditions récalcitrantes.

Si une infection se développe, l'utilisation des pansements occlusifs doit être interrompue et un traitement antimicrobien approprié doit être instauré.

Aucun.

Les corticostéroïdes topiques sont contre-indiqués chez les patients ayant des antécédents d'hypersensibilité à l'un des composants de la préparation.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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.

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.

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.

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

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.

Nonclinical Toxicology

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 assay.

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

Pregnancy

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.

Nursing Mothers

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.

Pediatric Use

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.

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 (ACTH_1-24) stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Geriatric Use

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.

WARNINGS

No information provided.

PRECAUTIONS

General

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.

Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings.

Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing 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. 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.

As with any topical corticosteroid product, prolonged use may produce atrophy of the skin and subcutaneous tissues. When used on intertriginous or flexor areas, or on the face, this may occur even with short-term use.

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 the 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 or the effect on fertility of topical corticosteroids.

Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results.

Pregnancy Category C

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women or 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 could 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, caution should be exercised when topical corticosteroids are administered to a nursing woman.

Pediatric Use

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced hypothalmic-pituitary-adrenal (HPA) axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio. 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.

Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

Expérience des essais cliniques

Étant donné que les études cliniques sont menées dans des conditions très variables, les taux d'effets indésirables observés dans les études cliniques d'un médicament ne peuvent pas être directement comparés aux taux dans les études cliniques d'un autre médicament et peuvent ne pas refléter les taux observés dans la pratique.

Dans les essais cliniques, un total de 443 sujets adultes atteints de dermatite atopique ou de psoriasis de type plaque ont été traités une fois par jour ou deux fois par jour avec de la crème VANOS pendant 2 semaines. Les effets indésirables les plus fréquemment observés dans ces essais cliniques étaient les suivants:

Tableau 1: Effets indésirables les plus fréquemment observés (≥ 1%) dans les essais cliniques pour adultes

La sécurité chez les patients âgés de 12 à 17 ans était similaire à celle observée chez les adultes.

Expérience de post-marquage

Les effets indésirables suivants ont été identifiés lors de l'utilisation post-approbation de la crème VANOS :

Conditions du site d'administration: décoloration, érythème, irritation, prurit, gonflement, douleur et état aggravés.

Troubles du système immunitaire: hypersensibilité.

Troubles du système nerveux: maux de tête et vertiges.

Troubles de la peau et des tissus sous-cutanés: acné, peau sèche, éruption cutanée, exfoliation cutanée et oppression cutanée.

Étant donné que ces réactions sont rapportées volontairement à partir d'une population de taille incertaine, il n'est pas toujours possible d'estimer de manière fiable leur fréquence ou d'établir une relation causale avec l'exposition au médicament.

Les effets indésirables locaux suivants sont rarement rapportés avec les corticostéroïdes topiques, mais peuvent survenir plus fréquemment avec l'utilisation de pansements occlusifs. Ces réactions sont répertoriées dans un ordre d'occurrence décroissant approximatif :

La crème VANOS appliquée par voie topique peut être absorbée en quantités suffisantes pour produire des effets systémiques.

Les corticostéroïdes appliqués par voie topique peuvent être absorbés en quantités suffisantes pour produire des effets systémiques (voir PRÉCAUTIONS).