Cutivate Lotion

Dosage Forms And Strengths

Lotion, 0.05%. Each gram of CUTIVATE Lotion contains 0.5 mg fluticasone propionate in a white to off-white lotion base. CUTIVATE® Lotion is supplied in 120 mL bottles.

Storage And Handling

CUTIVATE® (fluticasone propionate) Lotion, 0.05% is white to off-white in color, and supplied as follows:

120 mL bottle NDC 10337-434-04

Store between 15° and 30°C (59° and 86° F).

Do not refrigerate, and keep container tightly closed.

Distributed by: PharmaDerm, a division of Fougera Pharmaceuticals Inc., Melville, New York 11747. Revised: Jan 2015

• Allergy Drugs: Prescription and OTC
• Atopic Dermatitis

CUTIVATE® Lotion is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of atopic dermatitis in patients 3 months of age or older.

Apply a thin film of CUTIVATE® Lotion to the affected skin areas once daily. Rub in gently.

Discontinue use when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary.

The safety and efficacy of CUTIVATE® Lotion have not been established beyond 4 weeks of use.

Avoid use with occlusive dressings or application to the diaper area [see Warnings and Precautions (5.1) and (5.2)].

CUTIVATE® Lotion is for topical use only, and not for ophthalmic, oral, or intravaginal use.

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

Topical corticosteroids, including CUTIVATE® Lotion, can produce reversible HPA axis suppression with the potential for glucocorticoid insufficiency. Risk factors that predispose to HPA axis suppression include the use of high-potency topical corticosteroids, large treatment surface areas, prolonged use, use under occlusion, concomitant use of more than one corticosteroid-containing product, altered skin barrier, and liver failure. 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 a less potent topical corticosteroid. Evaluation of HPA axis suppression may be done by using the cosyntropin stimulation test.

The effects of CUTIVATE® Lotion on HPA axis function in pediatric patients were investigated in two trials. Among a total of 89 evaluable subjects from the two trials who were treated with CUTIVATE® Lotion twice daily for 3 to 4 weeks, a single subject with >90% body surface area treated showed laboratory evidence of transient suppression immediately post-treatment. The post cosyntropin stimulation test serum cortisol returned to a normal level (22.1µg/dL) within one week of the final treatment visit [see Use In Specific Populations (8.4) and Clinical Pharmacology (12.2)].

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.

Local Adverse Reactions

CUTIVATE® Lotion may cause local adverse reactions, including skin atrophy [see Adverse Reactions (6.1 , 6.2)]. The risk is greater with use under occlusion and with higher potency products.

CUTIVATE® Lotion contains the excipient imidurea which releases formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin. Avoid using CUTIVATE® Lotion in individuals with hypersensitivity to formaldehyde as it may prevent healing or worsen dermatitis.

If irritation develops, discontinue CUTIVATE® Lotion and institute appropriate therapy.

Allergic Contact Dermatitis
Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. Such an observation can be corroborated with appropriate diagnostic patch testing. Discontinue CUTIVATE® Lotion if appropriate.

Concomitant Skin Infections

If skin infections are present or develop at the treatment site, an appropriate antimicrobial agent should be used. If a favorable response does not occur promptly, discontinue use of CUTIVATE® Lotion 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® Lotion in atopic dermatitis is unknown.

Pharmacodynamics

Vasoconstrictor Assay

Trials performed with CUTIVATE® Lotion 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.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

In an open label HPA axis suppression trial (Trial A), 42 pediatric subjects (ages 4 months to <6 years) with moderate to severe atopic dermatitis covering ≥ 35% Body Surface Area (BSA) who were treated with an exaggerated dosing regimen of CUTIVATE® Lotion twice daily (rather than the indicated dosing regimen of once daily) for at least 3 to 4 weeks were assessed for HPA axis suppression. The mean BSA treated was 65%. None of the 40 evaluable subjects were suppressed. The criterion for HPA axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter at 30-minutes after cosyntropin stimulation.

Another open label HPA axis suppression trial (Trial B) enrolled 56 pediatric subjects (ages 3 months to 11 months) with moderate to severe atopic dermatitis covering ≥ 35% BSA. Subjects were treated with an exaggerated dosing regimen for of CUTIVATE® Lotion twice daily over a period of 3 or 4 weeks. The mean BSA treated was 54%. Out of 56 subjects, 49 were considered evaluable with respect to their adrenal axis function post-treatment. One of 49 subjects showed laboratory evidence of suppression immediately post treatment. The criterion for HPA axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter at 30-minutes after cosyntropin stimulation. Repeated test one week later showed the post cosyntropin stimulation testing serum cortisol returned to normal level (22.1 µg/dL). This 4-month old subject had a baseline treatment BSA of 94% and was reported to have received 100% of the twice-daily applications of CUTIVATE® Lotion over the 27 day treatment period.

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.

Plasma fluticasone levels were measured in a subset of subjects 2 to 5 years and 11 months of age in HPA axis suppression trial (Trial A) described above. A total of 13 (62%) of 21 subjects tested had measurable fluticasone at the end of 3 to 4 weeks of treatment. The mean ± SD fluticasone plasma concentration was 0.16 ± 0.23 ng/mL. Three subjects aged 3, 4, and 4 years had fluticasone concentrations over 0.30 ng/mL, with one of them having a concentration of 0.82 ng/mL. No data were obtained for subjects < 2 years of age.

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.

CUTIVATE® (fluticasone propionate) Lotion, 0.05% is white to off-white in color, and supplied as follows:

120 mL bottle NDC 10337-434-04

Store between 15° and 30°C (59° and 86° F).

Do not refrigerate, and keep container tightly closed.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Administration Instructions
Advise the patient of appropriate CUTIVATE® Lotion administration instructions, including those that will mitigate HPA-Axis suppression [see Warnings and Precautions (5.1)] and local adverse reactions [see Warnings and Precautions (5.2)]:

Local Adverse Reactions
Advise the patient to report any signs of local adverse reactions to their healthcare provider [see Warnings and Precautions (5.2)].

Patent No. 7300669

46154831B/46155409B
Revised: 07/2015
#192

PharmaDerm® NDC 10337-434-04

CUTIVATE®
(fluticasone propionate)
Lotion, 0.05%

For topical use only –
Not for ophthalmic, oral
or intravaginal use.

Rx only

120 mL