VANOS® (fluocinonide) cream, 0.1% contains fluocinonide, a synthetic corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. Fluocinonide has the chemical name 6 alpha, 9 alpha-difluoro-11 beta, 21-dihydroxy-16 alpha, 17 alpha-isopropylidenedioxypregna-1, 4-diene-3,20-dione 21-acetate. Its chemical formula is C₂₆H₃₂F₂O₇ and it has a molecular weight of 494.58.

It has the following chemical structure:

Fluocinonide is an almost odorless white to creamy white crystalline powder. It is practically insoluble in water and slightly soluble in ethanol.

Each gram of VANOS® cream contains 1 mg micronized fluocinonide in a cream base of propylene glycol USP, dimethyl isosorbide, glyceryl stearate (and) PEG-100 stearate, glyceryl monostearate NF, purified water USP, carbopol 980 NF, diisopropanolamine, and citric acid USP.

Last updated on RxList: 12/29/2008

VANOS® (fluocinonide) cream, 0.1%, is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses in patients 12 years of age or older (See PRECAUTIONS: Pediatric Use).

Treatment beyond 2 consecutive weeks is not recommended and the total dosage should not exceed 60 g/week because the safety of VANOS® cream for longer than 2 weeks has not been established and because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Therapy should be discontinued when control of the disease is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. Do not use more than half of the 120 g tube per week.

For psoriasis, apply a thin layer of VANOS® cream once or twice daily to the affected skin areas as directed by a physician. Twice daily application for the treatment of psoriasis has been shown to be more effective in achieving treatment success during 2 weeks of treatment.

For atopic dermatitis, apply a thin layer of VANOS® cream once daily to the affected skin areas as directed by a physician. Once daily application for the treatment of atopic dermatitis has been shown to be as effective as twice daily treatment in achieving treatment success during 2 weeks of treatment (See Clinical Studies).

For corticosteroid responsive dermatoses, other than psoriasis or atopic dermatitis, apply a thin layer of VANOS® cream once or twice daily to the affected areas as directed by a physician.

Treatment with VANOS® cream should be limited to 2 consecutive weeks, and no more than 60 g/week should be used. Do not use more than half of the 120 g tube per week.

Therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

VANOS® (fluocinonide) cream 0.1% is supplied in tubes as follows:

30 g (NDC 99207-525-30)
60 g (NDC 99207-525-60)
120 g (NDC 99207-525-10)

Store at controlled room temperature: 15º to 30ºC (59º to 86ºF).

Manufactured for: Medicis, The Dermatology Company, Scottsdale, AZ 85258. Manufactured by: Contract Pharmaceuticals Ltd. Mississauga, Ontario Canada L5N 6L6. Prescribing information as of December 2007. FDA Rev date: 12/13/2006

Last updated on RxList: 12/29/2008

In clinical trials, a total of 443 adult patients with atopic dermatitis or plaque-type psoriasis were treated once daily or twice daily with VANOS® cream for 2 weeks. The most commonly observed adverse events in these clinical trials were as follows:

Table 3: most Commonly Observed Adverse Events in Adult Clinical Trials

Adverse Event	VANOS® cream, once daily (n=216)	VANOS® cream, twice daily (n=227)	Vehicle cream, once or twice daily (n=211)
Headache	8/216 (3.7%)	9/227 (4.0%)	6/211 (2.8%)
Application Site Burning	5/216 (2.3%)	4/227 (1.8%)	14/211 (6.6%)
Nasopharyngitis	2/216 (0.9%)	3/227 (1.3%)	3/211 (1.4%)
Nasal Congestion	3/216 (1.4%)	1/227 (0.4%)	0
Unspecified Application Site Reaction	1/216 (0.4%)	1/227 (0.4%)	3/211 (1.4%)

No other adverse events were reported by more than 1 subject receiving active treatment. The incidence of all adverse events was similar between the active treatment groups and the vehicle control groups. Safety in patients 12 to 17 years of age was similar to that observed in adults.

The following additional local adverse reactions have been reported with topical corticosteroids, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.

Systemic absorption of topical corticosteroids has produced hypothalamic-pituitary-adrenal (HPA) axis suppression manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

No information provided.

Last updated on RxList: 12/29/2008

No information provided.

General

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for gluococorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure.

Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA-axis suppression. This may be done by using cosyntropin (ACTH_1-24) stimulation testing. Patients should not be treated with VANOS® cream for more than 2 weeks at a time and only small areas should be treated at any time due to the increased risk of HPA axis suppression.

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 corticosteroid. Recovery of HPA-axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

Application of VANOS® cream, 0.1% twice daily for 14 days in 18 adult patients with plaque-type psoriasis (10–50% BSA, mean 19.6% BSA) and 31 adult patients (17 treated once daily; 14 treated twice daily) with atopic dermatitis (2–10% BSA, mean 5% BSA) showed demonstrable HPA-axis suppression in 2 patients with psoriasis (with 12% and 25% BSA) and 1 patient with atopic dermatitis (treated once daily, 4% BSA) where the criterion for HPA-axis suppression is a serum cortisol level of less than or equal to 18 micrograms per deciliter 30 minutes after stimulation with cosyntropin (ACTH_1-24) (See CLINICAL PHARMACOLOGY).

Controlled clinical efficacy studies of VANOS® cream in pediatric patients younger than 17 years of age have not been conducted; (See PRECAUTIONS: Pediatric Use).

HPA-axis suppression has not been evaluated in psoriasis patients who are less than 18 years of age. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. (See PRECAUTIONS: Pediatric Use).

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.

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.

VANOS® cream should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.

Information for the Patient

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:

1. 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.
2. VANOS® cream should not be used for any disorder other than that for which it was prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped, so as to be occlusive unless directed by the physician.
4. Patients should report to their physician any signs of local adverse reactions.
5. Other corticosteroid-containing products should not be used with VANOS® cream without first talking to the physician.
6. 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.
7. 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.
8. Patients should inform their physicians that they are using VANOS® cream if surgery is contemplated.
9. Patients should wash their hands after applying medication.

Laboratory Tests

The cosyntropin (ACTH_1-24) stimulation test may be helpful in evaluating patients for HPA-axis suppression.

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 fluocinonide.

Fluocinonide revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames test and an in vitro chromosomal aberration assay in human lymphocytes). However, fluocinonide was positive for clastogenic potential when tested in the in vivo mouse micronucleus assay.

Pregnancy Category C: Teratogenic Effects

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.

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.

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.

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 insuf- ficiency 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. In general, dose selection for an elderly patient should be cautious.

Last updated on RxList: 12/29/2008

Topically applied VANOS® cream can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).

VANOS® cream is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Last updated on RxList: 12/29/2008

Like other topical corticosteroids, VANOS® (fluocinonide) cream, has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of topical corticosteroids, in general, is unclear. However, corticosteroids are thought to act by induction of phospholipase A₂ inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachadonic acid. Arachadonic acid is released from membrane phospholipids by phospholipase A₂.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/ or other disease processes in the skin may increase percutaneous absorption.

Vasoconstrictor studies performed with VANOS® cream, 0.1% in healthy subjects indicate that it is in the super-high range of potency as compared with other topical corticosteroids; however, similar blanching scores do not necessarily imply therapeutic equivalence.

Application of VANOS® cream, 0.1% twice daily for 14 days in 18 adult patients with plaque-type psoriasis (10–50% BSA, mean 19.6% BSA) showed demonstrable HPA-axis suppression in 2 patients (with 12% and 25% BSA) where the criterion for HPAaxis suppression is a serum cortisol level of less than or equal to 18 micrograms per deciliter 30 minutes after stimulation with cosyntropin (ACTH_1-24) (See PRECAUTIONS: general and Pediatric Use).

HPA-axis suppression has not been evaluated in psoriasis patients who are less than 18 years of age. HPA-axis suppression has been evaluated in pediatric patients with atopic dermatitis 12 to 18 years of age (See PRECAUTIONS: Pediatric Use).

Clinical Studies

Two adequate and well-controlled efficacy and safety studies of VANOS® cream have been completed, one in adult patients with plaque-type psoriasis (Table 1), and one in adult patients with atopic dermatitis (Table 2). In each of these studies, patients with between 2% and 10% body surface area involvement at Baseline treated all affected areas either once daily or twice daily with VANOS® cream for 14 consecutive days. The primary measure of efficacy was the proportion of patients whose condition was cleared or almost cleared at the end of treatment. The results of these studies are presented in the tables below as percent and number of patients achieving treatment success at Week 2.

Table 1: Plaque-Type Psoriasis in Adults

	VANOS® cream, once daily (n=107)	Vehicle, once daily (n=54)	VANOS® cream, twice daily (n=107)	Vehicle, twice daily (n=55)
Patients cleared	0 (0)	0 (0)	6 (6%)	0 (0)
Patients achieving treatment success*	19 (18%)	4 (7%)	33 (31%)	3 (5%)
*Cleared or almost cleared

Table 2: Atopic Dermatitis in Adults

	VANOS® cream, once daily (n=109)	Vehicle, once daily (n=50)	VANOS® cream, twice daily (n=102)	Vehicle, twice daily (n=52)
Patients cleared	11 (10%)	0 (0)	17 (17%)	0 (0)
Patients achieving treatment success*	64 (59%)	6 (12%)	58 (57%)	10 (19%)
*Cleared or almost cleared

No efficacy studies have been conducted to compare VANOS® (fluocinonide) cream, 0.1% with any other topical corticosteroid product, including fluocinonide cream 0.05%.

Last updated on RxList: 12/29/2008

Safety Information

• VANOS™ Cream is a corticosteroid (steroid hormone) approved to relieve the inflammation and itching caused by certain skin conditions that respond to treatment with corticosteroids in patients 12 years of age or older.
• Treatment should not exceed two weeks or 60 grams per week, because the safety of using VANOS™ Cream beyond two weeks has not been established and because it may reduce levels of hormones that regulate your body's immune system and energy levels (HPA-axis suppression). Do not use more than half of the 120 gram tube in a week.
• You should stop using VANOS™ Cream when your skin condition is under control. If you see no improvement in two weeks, contact your doctor.
• After you stop using VANOS Cream, your adrenal gland may temporarily be unable to make enough of the hormones your body needs to adapt to stress (glucocorticosteroid insufficiency). HPA-axis suppression occurred in two out of 18 adult patients with psoriasis treated twice daily for two weeks and in one out of 31 adult patients with atopic dermatitis treated once daily for two weeks. How often HPA-axis suppression occurs in psoriasis patients who are less than 18 years of age has not been determined. Because children have more skin compared to their body weight, they have a greater risk than adults of HPA-axis suppression and Cushing's syndrome (a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks) when they apply corticosteroids (steroid hormones) to the skin.
• If irritation develops, stop using VANOS™ Cream and call your doctor.
• VANOS™ Cream should not be used on the face, groin, or underarms; or for treatment of rosacea (flushed skin and pimples) or rash around the mouth.
• The safety and efficacy in patients younger than 12 years of age have not been established.
• The most commonly reported adverse events were headache, burning at the application site, inflammation of the nasal passages and upper throat, and nasal congestion.

Last updated on RxList: 12/29/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

FLUOCINONIDE 0.1% CREAM - TOPICAL

(flew-oh-SIH-no-nide)

COMMON BRAND NAME(S): Vanos

USES: This medication is used to treat a variety of skin conditions (e.g., psoriasis, eczema, dermatitis, allergies, rash). Fluocinonide reduces the swelling, itching, and redness that can occur in these types of conditions. It also can heal the rough, scaly patches on the skin seen with psoriasis. This medication is a very strong (super-high-potency) corticosteroid.

HOW TO USE: Use this medication on the skin only. Do not use it on the face, groin, or underarms unless directed to do so by your doctor.

Before applying the medication, clean and dry the affected area. Apply a thin film of the medication to the affected area and gently rub in, once daily if treating eczema or 1-2 times daily if treating psoriasis. If treating other skin conditions, apply this medication 1-2 times daily or as directed by your doctor. Do not wrap, cover, or bandage the area unless directed to do so by your doctor. If used in the diaper area on an infant, do not use tight-fitting diapers or plastic pants.

After applying the medication, wash your hands unless you are using this medication to treat the hands. If applying this medication near the eyes, avoid getting it in the eyes as this may worsen or cause glaucoma. Also avoid getting this medication in the nose or mouth. If you get the medication in these areas, rinse with plenty of water.

Use this medication only for the condition prescribed. Do not use it for longer than 2 weeks in a row or use more than 60 grams per week unless directed to do so by your doctor.

Inform your doctor if your condition persists or worsens after 2 weeks.

SIDE EFFECTS: Burning, stinging, itching, dryness, or redness may occur when this medication is first applied to the skin. This should disappear in a few days as your body adjusts to the medication. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor if any of these unlikely but serious side effects occur: stretch marks, skin thinning/discoloration, acne, extreme/unwanted hair growth, "hair bumps" (folliculitis).

Skin infections can become worse when this medication is used. Notify your doctor promptly if redness, swelling, or irritation does not improve.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using fluocinonide, tell your doctor or pharmacist if you are allergic to it; or to other corticosteroids (e.g., hydrocortisone, prednisone); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: poor blood circulation, immune system problems, certain skin conditions (rosacea, perioral dermatitis).

Do not use if there is an infection or sore present in the area to be treated.

Though very unlikely, it is possible this medication will be absorbed into your bloodstream. This may have undesirable consequences that may require additional corticosteroid treatment. This is especially true for children and those who have used this drug for an extended time, especially if they also have serious medical problems such as serious infections, injuries, or surgeries. This precaution applies for up to one year after stopping use of this drug. Tell your doctor immediately if any of the following side effects occur: vision problems, persistent headache, increased thirst/urination, unusual weakness, unusual weight loss, dizziness.

Consult your doctor or pharmacist for more details, and inform them that you use or have used this medication.

Children may be more sensitive to the effects of too much steroid hormone. Though it is unlikely to occur with corticosteroids applied to the skin, this medication may affect growth in infants and children if used for long periods. Monitor your child's height and rate of growth from time to time.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk when applied to the skin. Similar medications pass into breast milk when taken by mouth. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: corticosteroids taken by mouth (e.g., prednisone), drugs that lower the immune system (e.g., cyclosporine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for other skin problems unless told to do so by your doctor. A different medication may be necessary in those cases.

Laboratory and/or medical tests (e.g., adrenal gland function tests, morning cortisol blood test) may be performed periodically to monitor your progress or check for side effects if you use this drug for 2 weeks or longer, apply it over large areas of the body, or bandage/wrap the treated areas. Consult your doctor for more details.

Inform all your doctors that you use or have used this medication.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.