August 3, 2015
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Cutivate Lotion

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Cutivate Lotion




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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].

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 and CLINICAL PHARMACOLOGY].

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]. 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.

Patient Counseling Information

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] and local adverse reactions [see WARNINGS AND PRECAUTIONS]:

  • Discontinue therapy when control is achieved in less than 4 weeks; if no improvement is seen within 2 weeks, contact the healthcare provider.
  • Avoid contact with the eyes.
  • Do not bandage the treated skin area, or cover or wrap it to cause occlusion unless directed by the healthcare provider.
  • Do not use CUTIVATE® Lotion in the treatment of diaper dermatitis unless directed by the healthcare provider, as diapers or plastic pants may constitute occlusive dressing and enhance absorption.
  • Do not use on the face, underarms, or groin areas unless directed by the healthcare provider.
Local Adverse Reactions

Advise the patient to report any signs of local adverse reactions to their healthcare provider [see WARNINGS AND PRECAUTIONS].

  • Advise patients to report to their healthcare provider if they are allergic to formaldehyde.

Nonclinical Toxicology

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).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Therefore, CUTIVATE® Lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Systemic embryofetal development studies were conducted in mice, rats and rabbits.

Subcutaneous doses of 15, 45 and 150 μg/kg/day of fluticasone propionate were administered to pregnant female mice from gestation days 6 to 15. A teratogenic effect characteristic of corticosteroids (cleft palate) was noted after administration of 45 and 150 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 15 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Subcutaneous doses of 10, 30 and 100 μg/kg/day of fluticasone propionate were administered to pregnant female rats in two embryofetal development studies (one study administered fluticasone propionate from gestation days 6 to 15 and the other study from gestation days 7 to 17). In the presence of maternal toxicity, fetal effects noted at 100 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) included decreased fetal weights, omphalocele, cleft palate, and retarded skeletal ossification. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 10 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Subcutaneous doses of 0.08, 0.57 and 4 μg/kg/day of fluticasone propionate were administered to pregnant female rabbits from gestation days 6 to 18. Fetal effects noted at 4 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) included decreased fetal weights, cleft palate and retarded skeletal ossification. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 0.57 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Oral doses of 3, 30 and 300 μg/kg/day fluticasone propionate were administered to pregnant female rabbits from gestation days 8 to 20. No fetal or teratogenic effects were noted at oral doses up to 300 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study. However, no fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration.

Fluticasone propionate crossed the placenta following administration of a subcutaneous or an oral dose of 100 μg/kg tritiated fluticasone propionate to pregnant rats.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and can 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 CUTIVATE® Lotion is administered to a nursing woman.

Pediatric Use

CUTIVATE® Lotion may be used in pediatric patients as young as 3 months of age. The safety and effectiveness of CUTIVATE® Lotion in pediatric patients below 3 months of age have not been established.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic effects when treated with topical drugs. They are, therefore, also at greater risk of HPA axis suppression and adrenal insufficiency upon the use of topical corticosteroids [see WARNINGS AND PRECAUTIONS].

In an HPA axis suppression trial, none of the 40 evaluable pediatric subjects, 4 months old to < 6 years old, with moderate to severe atopic dermatitis covering ≥ 35% Body Surface Area (BSA) who were treated with an exaggerated dosing regimen (twice daily) of CUTIVATE® Lotion experienced adrenal suppression (defined as a 30-minute post-stimulation cortisol level ≤ 18 micrograms/dL) [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

In another HPA axis suppression trial, one of 49 (2%) evaluable pediatric subjects, 3 months to 11 months old, with moderate to severe atopic dermatitis covering ≥ 35% Body Surface Area (BSA) who applied an exaggerated dosing regimen (twice daily) of CUTIVATE® Lotion experienced reversible adrenal suppression (defined as a 30-minute post-stimulation cortisol level ≤ 18 micrograms/dL) following 4 weeks of therapy [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Systemic effects such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high-potency topical corticosteroids, or concomitant use of more than one corticosteroid product.

Local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients.

Parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis unless directed by a physician. CUTIVATE® Lotion should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing.

Geriatric Use

A limited number of patients above 65 years of age have been treated with CUTIVATE® Lotion in US and non-US clinical trials. Specifically only 8 patients above 65 years of age were treated with CUTIVATE® Lotion in controlled clinical trials. The number of patients is too small to permit separate analyses of efficacy and safety.

Last reviewed on RxList: 1/28/2015
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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