pimecrolimus 10 MG/ML Topical Cream [Elidel]

INDICATIONS AND USAGE Pimecrolimus Cream, 1% is indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. Pimecrolimus Cream, 1% is not indicated for use in children less than 2 years of age [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ] . Pimecrolimus Cream, 1% is a calcineurin inhibitor immunosuppressant indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. ( 1 )

DOSAGE AND ADMINISTRATION Apply a thin layer of Pimecrolimus Cream, 1% to the affected skin twice daily. The patient should stop using Pimecrolimus Cream, 1% when signs and symptoms (e.g., itch, rash and redness) resolve and should be instructed on what actions to take if symptoms recur. If signs and symptoms persist beyond 6 weeks, patients should be re-examined by their healthcare provider to confirm the diagnosis of atopic dermatitis. Continuous long-term use of Pimecrolimus Cream, 1% should be avoided, and application should be limited to areas of involvement with atopic dermatitis [see Warnings and Precautions (5.1) ] . The safety of Pimecrolimus Cream, 1% under occlusion, which may promote systemic exposure, has not been evaluated. Avoid use of Pimecrolimus Cream, 1% with occlusive dressings. • Apply a thin layer of Pimecrolimus Cream, 1% to the affected skin twice daily. ( 2 ) • If signs and symptoms persist beyond 6 weeks, patients should be re-examined. ( 2 ) • Continuous long-term use of Pimecrolimus Cream, 1% should be avoided. ( 2 ) • Avoid use with occlusive dressings. ( 2 )

WARNINGS AND PRECAUTIONS • Should not be used in immunocompromised adults and children, including patients on systemic immunosuppressive medications. ( 5.1 ) • Avoid treatment on malignant or pre-malignant skin conditions, as these can present as dermatitis. ( 5.2 ) • Should not be used in patients with Netherton’s Syndrome or skin diseases with a potential for increased systemic absorption. ( 5.2 ) 5.1 Risk of Immunosuppression Prolonged systemic use of calcineurin inhibitors for sustained immunosuppression in animal studies and transplant patients following systemic administration has been associated with an increased risk of infections, lymphomas, and skin malignancies. These risks are associated with the intensity and duration of immunosuppression. Based on this information and the mechanism of action, there is a concern about a potential risk with the use of topical calcineurin inhibitors, including Pimecrolimus Cream, 1%. While a causal relationship has not been established, rare cases of skin malignancy and lymphoma have been reported in patients treated with topical calcineurin inhibitors, including Pimecrolimus Cream, 1%. Therefore: • Continuous long-term use of topical calcineurin inhibitors, including Pimecrolimus Cream, 1%, in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis. • Pimecrolimus Cream, 1% is not indicated for use in children less than 2 years of age. • Pimecrolimus Cream, 1% should not be used in immunocompromised adults and children, including patients on systemic immunosuppressive medications. • If signs and symptoms of atopic dermatitis do not improve within 6 weeks, patients should be re-examined by their healthcare provider and their diagnosis be confirmed. • The safety of Pimecrolimus Cream, 1% has not been established beyond 1 year of non-continuous use. 5.2 Application to Malignant or Pre-malignant Skin Conditions The use of Pimecrolimus Cream, 1% should be avoided on malignant or pre-malignant skin conditions. Malignant or pre-malignant skin conditions, such as cutaneous T-cell lymphoma (CTCL), can present as dermatitis. Pimecrolimus Cream, 1% should not be used in patients with Netherton’s Syndrome or other skin diseases where there is the potential for increased systemic absorption of pimecrolimus. The safety of Pimecrolimus Cream, 1% has not been established in patients with generalized erythroderma. The use of Pimecrolimus Cream, 1% may cause local symptoms such as skin burning (burning sensation, stinging, soreness) or pruritus. Localized symptoms are most common during the first few days of Pimecrolimus Cream, 1% application and typically improve as the lesions of atopic dermatitis resolve [see Adverse Reactions ( 6.1 )] . 5.3 Bacterial and Viral Skin Infections Before commencing treatment with Pimecrolimus Cream, 1%, bacterial or viral infections at treatment sites should be resolved. Trials have not evaluated the safety and efficacy of Pimecrolimus Cream, 1% in the treatment of clinically infected atopic dermatitis. While patients with atopic dermatitis are predisposed to superficial skin infections including eczema herpeticum (Kaposi’s varicelliform eruption), treatment with Pimecrolimus Cream, 1% may be independently associated with an increased risk of varicella zoster virus infection (chickenpox or shingles), herpes simplex virus infection, or eczema herpeticum. In clinical trials, 15/1544 (1%) cases of skin papilloma (warts) were observed in subjects using Pimecrolimus Cream, 1%. The youngest subject was age 2 and the oldest was age 12. In cases where there is worsening of skin papillomas or they do not respond to conventional therapy, discontinuation of Pimecrolimus Cream, 1% should be considered until complete resolution of the warts is achieved. 5.4 Patients with Lymphadenopathy In clinical trials, 14/1544 (0.9%) cases of lymphadenopathy were reported while using Pimecrolimus Cream, 1%. These cases of lymphadenopathy were usually related to infections and noted to resolve upon appropriate antibiotic therapy. Of these 14 cases, the majority had either a clear etiology or were known to resolve. Patients who receive Pimecrolimus Cream, 1% and who develop lymphadenopathy should have the etiology of their lymphadenopathy investigated. In the absence of a clear etiology for the lymphadenopathy, or in the presence of acute infectious mononucleosis, Pimecrolimus Cream, 1% should be discontinued. Patients who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. 5.5 Sun Exposure During the course of treatment, it is prudent for patients to minimize or avoid natural or artificial sunlight exposure, even while Pimecrolimus Cream, 1% is not on the skin. The potential effects of Pimecrolimus Cream, 1% on skin response to ultraviolet damage are not known. 5.6 Immunocompromised Patients The safety and efficacy of Pimecrolimus Cream, 1% in immunocompromised patients have not been studied.

CONTRAINDICATIONS Pimecrolimus Cream, 1% is contraindicated in individuals with a history of hypersensitivity to pimecrolimus or any of the components of the cream. Pimecrolimus Cream, 1% is contraindicated in individuals with a history of hypersensitivity to pimecrolimus or any of the components of the cream. ( 4 , 6.2 )

Mechanism of Action The mechanism of action of pimecrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that pimecrolimus binds with high affinity to macrophilin-12 (FKBP-12) and inhibits the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T-cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin-2 and interferon gamma (Th1-type) and Interleukin-4 and Interleukin-10 (Th2-type) cytokine synthesis in human T-cells. In addition, pimecrolimus prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/IgE.