Pharmacokinetics

General -

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from 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.

Patients applying a potent 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 the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol 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 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.

Fluticasone propionate cream, 0.05% caused depression of A.M. plasma cortisol levels in 1 of 6 adult patients when used daily for 7 days in patients with psoriasis or eczema involving at least 30% of the body surface. After 2 days of treatment, this patient developed a 60% decrease from pretreatment values in the A.M. plasma cortisol level.

There was some evidence of corresponding decrease in the 24-hour urinary free cortisol levels. The A.M. plasma cortisol level remained slightly depressed for 48 hours but recovered by day 6 of treatment.

Fluticasone propionate cream, 0.05%, caused HPA axis suppression in 2 of 43 pediatric patients, ages 2 and 5 years old, who were treated for 4 weeks covering at least 35% of the body surface area. Follow-up testing 12 days after treatment discontinuation, available for 1 of the 2 subjects, demonstrated a normally responsive HPA axis (see PRECAUTIONS - Pediatric Use).

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).

The following 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 approximately decreasing order of occurrence: irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infections, skin atrophy, striae, hypertrichosis, and miliaria.

Fluticasone Propionate Cream, 0.05% may cause local cutaneous adverse reactions (see ADVERSE REACTIONS).

If irritation develops, Fluticasone Propionate Cream, 0.05% 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 Fluticasone Propionate Cream, 0.05% should be discontinued until the infection has been adequately controlled.

Fluticasone Propionate Cream, 0.05% should not be used in the presence of preexisting skin atrophy and should not be used where infection is present at the treatment site. Fluticasone Propionate Cream, 0.05% should not be used in the treatment of rosacea and perioral dermatitis.

Information for Patients -

Patients using topical corticosteroids should receive the following information and instructions:

1.

This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.

2.

This medication 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 as well as non-healing or worsening of skin condition.

5.

Parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis. Fluticasone Propionate Cream, 0.05% should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing (see DOSAGE AND ADMINISTRATION).

6.

This medication should not be used on the face, underarms, or groin areas unless directed by a physician.

7.

As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.

8.

Patients should report to their physician if they are allergic to formaldehyde.

Laboratory Tests -

The following tests may be helpful in evaluating patients for HPA axis suppression:

ACTH stimulation test

A.M. plasma cortisol test

Urinary free cortisol test

Carcinogenesis, Mutagenesis, Impairment of Fertility -

Two 18-month studies were performed in mice to evaluate the carcinogenic potential of fluticasone propionate when given topically (as an 0.05% ointment) and orally. No evidence of carcinogenicity was found in either study.

Fluticasone propionate was not mutagenic in the standard Ames test, E. coli fluctuation test, S. cerevisiae gene conversion test, or Chinese Hamster ovarian cell assay. It was not clastogenic in mouse micronucleus or cultured human lymphocyte tests.

In a fertility and general reproductive performance study in rats, fluticasone propionate administered subcutaneously to females at up to 50 mcg/kg per day and to males at up to 100 mcg/kg per day (later reduced to 50 mcg/kg per day) had no effect upon mating performance or fertility. These doses are approximately 15 and 30 times, respectively, the human systemic exposure following use of the recommended human topical dose of fluticasone propionate cream, 0.05%, assuming human percutaneous absorption of approximately 3% and the use in a 70-kg person of 15 g/day.

Pregnancy:

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 human milk. Because many drugs are excreted in human milk, caution should be exercised when Fluticasone Propionate Cream, 0.05% is administered to a nursing woman.

Pediatric Use -

Fluticasone Propionate Cream, 0.05% contains the excipient imidurea which releases formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin. Fluticasone Propionate Cream, 0.05% should not be used in individuals with hypersensitivity to formaldehyde as it may prevent healing or worsen dermatitis.

Fluticasone Propionate Cream, 0.05% should be discontinued if control is achieved before 4 weeks. If no improvement is seen within 2 weeks, contact a physician. The safety and efficacy of drug use for longer than 4 weeks in this population have not been established.

The safety and efficacy of Fluticasone Propionate Cream, 0.05% in pediatric patients below 3 months of age have not been established.

Parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis unless directed by the physician. Fluticasone Propionate Cream, 0.05% should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing.

Fluticasone propionate cream, 0.05% caused HPA axis suppression in 2 of 43 pediatric patients, ages 2 and 5 years old, who were treated for 4 weeks covering at least 35% of the body surface area. Follow-up testing 12 days after treatment discontinuation, available for 1 of the 2 subjects, demonstrated a normally responsive HPA axis (see ADVERSE REACTIONS). Adverse effects including striae have been reported with use of topical corticosteroids in pediatric patients.

HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an 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.

Geriatric Use -

A limited number of patients above 65 years of age (n=126) have been treated with fluticasone propionate cream, 0.05% in US and non-US clinical trials. While the number of patients is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger patients. Based on available data, no adjustment of dosage of Fluticasone Propionate Cream, 0.05% in geriatric patients is warranted.

Clinical Trial Experience -

In controlled clinical trials of twice-daily administration, the total incidence of adverse reactions associated with the use of fluticasone propionate cream, 0.05% was approximately 4%. These adverse reactions were usually mild; self-limiting; and consisted primarily of pruritus, dryness, numbness of fingers, and burning. These events occurred in 2.9%, 1.2%, 1.0%, and 0.6% of patients, respectively.

Two clinical studies compared once- to twice-daily administration of fluticasone propionate cream, 0.05% for the treatment of moderate to severe eczema. The local drug-related adverse events for the 491 patients enrolled in both studies are shown in Table 1. In the study enrolling both adult and pediatric patients, the incidence of local adverse events in the 119 pediatric patients ages 1 to 12 years was comparable to the 140 patients ages 13 to 62 years.

Fifty-one pediatric patients ages 3 months to 5 years, with moderate to severe eczema, were enrolled in an open-label HPA axis safety study. Fluticasone propionate cream, 0.05% was applied twice daily for 3 to 4 weeks over an arithmetic mean body surface area of 64% (range, 35% to 95%). The mean morning cortisol levels with standard deviations before treatment (prestimulation mean value = 13.76 ± 6.94 mcg/dL, poststimulation mean value = 30.53 ± 7.23 mcg/dL) and at end treatment (prestimulation mean value = 12.32 ± 6.92 mcg/dL, poststimulation mean value = 28.84 ± 7.16 mcg/dL) showed little change. In 2 of 43 (4.7%) patients with end-treatment results, peak cortisol levels following cosyntropin stimulation testing were ≤18 μg/dL, indicating adrenal suppression. Follow-up testing after treatment discontinuation, available for 1 of the 2 subjects, demonstrated a normally responsive HPA axis. Local drug-related adverse events were transient burning, resolving the same day it was reported; transient urticaria, resolving the same day it was reported; erythematous rash; dusky erythema, resolving within 1 month after cessation of fluticasone propionate cream, 0.05%; and telangiectasia, resolving within 3 months after stopping fluticasone propionate cream, 0.05%.

Post Marketing Experience -

Systemic adverse events with fluticasone propionate cream, 0.05% and fluticasone propionate ointment have included: immunosuppression/Pneumocystis carinii pneumonia/leukopenia/thrombocytopenia; hyperglycemia/glycosuria; Cushing’s syndrome; generalized body edema/blurred vision; and acute urticarial reaction (edema, urticaria, pruritus, and throat swelling).

The following localized adverse reactions have been reported during post approval use of fluticasone propionate cream, 0.05%: skin discoloration, erythema, irritation, edema/swelling, atrophy, contusion, dermatitis, pain, sepsis, hemorrhage, acneiform eruptions.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Atopic Dermatitis -

Apply a thin film of Fluticasone Propionate Cream, 0.05% to the affected skin areas once or twice daily. Rub in gently.

Other Corticosteroid-Responsive Dermatoses -

Apply a thin film of Fluticasone Propionate Cream, 0.05% to the affected skin areas twice daily. Rub in gently.

As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Fluticasone Propionate Cream, 0.05% should not be used with occlusive dressings. Fluticasone Propionate Cream, 0.05% should not be applied in the diaper area, as diapers or plastic pants may constitute occlusive dressings.

Geriatric Use -

In studies where geriatric patients (65 years of age or older, see PRECAUTIONS) have been treated with fluticasone propionate cream, 0.05%, safety did not differ from that in younger patients; therefore, no dosage adjustment is recommended.

Psoriasis Studies -

In 2 vehicle-controlled studies, fluticasone propionate cream, 0.05% applied twice daily was significantly more effective than the vehicle in the treatment of moderate to severe psoriasis. The investigator's global evaluation after 28 days of treatment is shown in Table 3.

The clinical signs of psoriasis were scored on a scale of 0=absent, 1=mild, 2=moderate, and 3=severe. The mean improvements over baseline in the clinical signs at the end of treatment are shown in Table 4.

Atopic Dermatitis Studies -

In 2 controlled 28-day studies, fluticasone propionate cream, 0.05% once daily was equivalent to fluticasone propionate cream, 0.05% twice daily in the treatment of moderate to severe eczema. The investigator's global evaluation after 28 days of treatment is shown in Table 5.

The clinical signs and symptoms of atopic dermatitis were scored on a scale of 0=absent, 1=mild, 2=moderate, and 3=severe. The mean improvements over baseline at the end of treatment are shown in Table 6.