Cutivate

Fluticasone, a corticosteroid, is used to reduce inflammation and relieve itching, redness, dryness, and scaling associated with various skin conditions.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression and Other Adverse Endocrine Effects

Topical corticosteroids, including Cutivate® Ointment, can produce reversible HPA axis suppression with the potential for clinical glucocorticoid insufficiency. Factors that predispose to HPA axis suppression include large treatment surface areas, prolonged use, use under occlusion, altered skin barrier, liver failure, and young age. Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.

If HPA axis suppression is suspected, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression.

Pediatric patients may be at greater risk of HPA axis suppression due to their higher skin surface area to body mass ratios [see Use in Specific Populations (8.4)].

HPA axis suppression may occur during or after withdrawal of treatment. If HPA axis suppression is suspected, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. Evaluation of HPA axis suppression may be done by using the cosyntropin stimulation test.

Local Adverse Reactions

Cutivate® Ointment may cause local adverse reactions, including skin atrophy [see Adverse Reactions (6.1 , 6.2)]. The risk is greater with use under occlusion.

Allergic Contact Dermatitis

Allergic contact dermatitis with topical corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation can be corroborated with appropriate diagnostic patch testing. Discontinue Cutivate® Ointment if appropriate.

Skin Infections

If concomitant skin infections are present or develop, use an appropriate antimicrobial. If a favorable response does not occur promptly, discontinue use of Cutivate® Ointment until the infection has been adequately controlled.

Mechanism of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Cutivate® Ointment in corticosteroid-responsive dermatoses is unknown.

Pharmacodynamics

Vasoconstrictor Assay

Studies performed with Cutivate® Ointment indicate that it is in the medium range of potency as demonstrated in vasoconstrictor trials in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

Pharmacokinetics

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

In a study of 6 healthy subjects applying 25 g of fluticasone propionate ointment 0.005% twice daily to the trunk and legs for up to 5 days under occlusion, plasma levels of fluticasone ranged from 0.08 to 0.22 ng/mL.

Distribution
The percentage of fluticasone propionate bound to human plasma proteins averaged 91%. Fluticasone propionate is weakly and reversibly bound to erythrocytes. Fluticasone propionate is not significantly bound to human transcortin.

Metabolism
No metabolites of fluticasone propionate were detected in an in vitro study of radiolabeled fluticasone propionate incubated in a human skin homogenate.

Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5-fluoromethyl carbothiolate grouping. This transformation occurs in 1 metabolic step to produce the inactive 17β-carboxylic acid metabolite, the only known metabolite detected in man. This metabolite has approximately 2000 times less affinity than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In an oral (gavage) mouse carcinogenicity study, doses of 0.1, 0.3 and 1 mg/kg/day fluticasone propionate were administered to mice for 18 months. Fluticasone propionate demonstrated no tumorigenic potential at oral doses up to 1 mg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study.

In a dermal mouse carcinogenicity study, 0.05% fluticasone propionate ointment (40 μl) was topically administered for 1, 3 or 7 days/week for 80 weeks. Fluticasone propionate demonstrated no tumorigenic potential at dermal doses up to 6.7 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study.

Fluticasone propionate revealed no evidence of mutagenic or clastogenic potential based on the results of five in vitro genotoxicity tests (Ames assay, E. coli fluctuation test, S. cerevisiae gene conversion test, Chinese hamster ovary cell chromosome aberration assay and human lymphocyte chromosome aberration assay) and one in vivo genotoxicity test (mouse micronucleus assay).

No evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to 50 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Cutivate® (fluticasone propionate) Ointment, 0.005% is a white to off-white translucent ointment supplied as follows: supplied as follows:

30 gram tubes NDC 10337-333-30
60 gram tubes NDC 10337-333-60

Store between 2° and 30°C (36° and 86° F).

PharmaDerm® NDC 10337-333-30

Cutivate®
(fluticasone propionate)
Ointment, 0.005%

For topical use only – Not for ophthalmic use.

Rx only

30 g

Applies to fluticasone topical: topical application cream, topical application lotion, topical application ointment

Along with its needed effects, fluticasone topical (the active ingredient contained in Cutivate) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fluticasone topical:

• Burning, itching, redness, or stinging of the skin
• hives or welts, skin rash
• raised, dark red, wart-like spots on the skin, especially when used on the face

• Burning, itching, and pain in hairy areas, pus at the root of the hair

• Darkening of the skin
• diarrhea
• dizziness
• fainting
• loss of appetite
• mental depression
• nausea
• thinning of the skin with easy bruising, especially when used on the face or where the skin folds together (eg, between the fingers)
• unusual tiredness or weakness
• vomiting

Some side effects of fluticasone topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Body aches or pain
• change in hearing
• chills
• common cold
• cough
• difficulty with breathing
• dry skin
• ear congestion
• ear drainage
• earache or pain in the ear
• fever
• headache
• increased hair growth on the forehead, back, arms, and legs
• lightheadedness
• loss of voice
• nasal congestion
• runny nose
• sneezing
• sore throat