Atopic dermatitis pimecrolimus

For the topical treatment of some chronic inflammatory skin diseases (like atopic dermatitis) immunosuppressive macrolides (like TRL and pimecrolimus) that permeate the inflamed epidermis are of benefit for patients. Severe side effects comparable to those after systemic application of TRL in transplanted patients (see above) have not been observed so far. For the treatment of psoriasis vulgaris these drugs are less effective. The CD2 antagonist alefacept may be a suitable alternative to allergic reactions. 

The evidence of the safety and efficacy of pimecrolimus was derived from studies primarily in patients with mild-to-moderate atopic dermatitis tacrolimus data was derived from moderate-to-severe patients. 

The topical immunomodulators tacrolimus (Protopic) and pimecrolimus (Elidel) inhibit calcineurin, which normally initiatives T-cell activation. These agents can be used on all parts of the body for prolonged periods without producing corticosteroid-induced adverse effects. Tacrolimus ointment 0.03% and 0.1% is applied twice daily the lower strength is preferred in children with moderate to severe atopic dermatitis. The most common adverse effect is transient itching and burning at the site of application. Pimecrolimus cream 1% is applied twice daily for mild to moderate atopic dermatitis in adults and children older than age 2. 

Pimecrolimus (58 Elidel ) Ascomycin Macrolactum antibiotic Semi-synthetic NP Microbial Inflammatory skin diseases and atopic dermatitis Blocks T-cell activation 505-517... 

Nghiem P, Pearson Q Langley RG. (2002) Tacrolimus and pimecrolimus From clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol 46 228-241. 

Allen BR, Lakhanpaul M, Morris A, Lateo S, Davies T, Scott G Cardno M, Ebelin ME, Burtin P, Stephenson TJ. (2003) Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients. 

Pimecrolimus (SDZ ASM 981, Elidel) is another recently approved macrolide immunosuppressant that acts by inhibiting calcineurin and blocking the release of proinflammatory cytokines from T lymphocytes. The parent compound, ascomycin, was originally isolated from Streptomyces hygroscopicus var ascomyceticus. Like tacrolimus, pimecrolimus is approved for the topical treatment of moderate to severe atopic dermatitis that is refractory to other therapies. Transient local irritation is a common side effect. 

Gisondi P, Ellis CN, Girolomoni G. Pimecrolimus in dermatology atopic dermatitis and beyond. Int J Clin Pract. 2005 59 969-974. 

Meurer, M., Fartasch, M., Albercht, G. et al. Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis. Dermatology 2004 208 365-72. 

Meurer, M., Folster-Holst, R., Wozel, G. et al. Pimecrolimus cream in the long-term management of atopic dermatitis in adults a six-month study. Dermatology 2002 205 271-7. 

Topical calcineurin inhibitors are also used to treat atopic dermatitis and include pimecrolimus (Elidel) and tacrolimus (Protopic).Treatment effects are seen in 1 to 3 weeks. Adverse reactions most commonly include burning. Although a causal relation has not been established, rare skin malignancy and lymphoma have been reported. 

Pimecrolimus is a non-steroidal ascomycin derivative with topical anti-inflammatory activity. In a 1% cream it is effective and safe in atopic dermatitis in infants, children, and adults (1-3), although its efficacy has been questioned (4). 

Eichenfield LF, Lucky AW, Boguniewicz M, Langley RG, Cherill R, Marshall K, Bush C, Graeber M. Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Acad Dermatol 2002 46(4) 495-504. 

Weinberg JM. Formulary review of therapeutic alternatives for atopic dermatitis focus on pimecrolimus. J Manag Care Pharm 2005 ll(l) 56-64. 

Anonymous. Pimecrolimus new preparation. Me-too too many risks, not beneficial enough in atopic dermatitis. Prescrire Int 2004 13(74) 209-12. 

Pimecrolimus and tacrolimus are calcineurin inhibitors capable of exerting a local immunomodulating effect that may serve to normalize hyperproliferation of epidermis. As topical agents, tacrolimus and pimecrolimus are approved for the treatment of atopic dermatitis however, regulatory approval regarding the efficacy of these agents in psoriasis is yet to be completed. 

Topical immunomodulators, tacrolimus, and pimecrolimus provide new options for patients with mild to severe cases of atopic dermatitis. 

Papp K, Ho V, Halber A, et al. Pimecrolimus (Elidel, SDZ ASM 981) cream 1 % is effective and safe in infants aged 3-23 months with atopic dermatitis. Pediatr Dermatol 2001 18(Suppl) 76 (Abstract). 

Pimecrolimus is a topical immunomodulater. It inhibits T-cell activation by blocking the transcription of early cytokines. It is indicated in short-term and intermittent longterm treatment of mild to moderate atopic dermatitis in nonimmunocompromised patients. 

Pimecrolimus 1% cream (Elidel), a macroMe derived from ascomycin, is FDA approved for the treatment of atopic dermatitis in patients older than 2 years of age. 

Recently, Novartis has begun development of a new macrolide immunosuppressant, an ascomycin derivative (pimecrolimus ASM 981 Fig. 7), in a topical formulation of a 1% cream. Preliminary data presented at several international conferences suggest that it may have benefit in mild atopic dermatitis with a good safety profile, but definitive studies have not yet been published. 

Pimecrolimus 1% cream (elidel), a macrolide derived from azomycin, is FDA-approved for the treatment of atopic dermatitis in patients >2 years of age. Its mechanism of action and side effect profile are similar to those of tacrolimus. Burning, while occurring in some patients, appears to be less common with pimecrohmus than with tacrolimus. In addition, pimecrolimus has less systemic absorption. Similar precautions with regard to UV exposure should be taken during treatment with pimecrolimus. 

Tumorigenicity The rates of tumors among patients with atopic dermatitis or eczema who used topical pimecrolimus have been evaluated in a retrospective cohort study of 953 064 subjects and controls [54 ]. The age- and sex-adjusted hazard ratio for all cancers was 1.15 (95% Cl = 0.99, 1.31). T-cell lymphoma was the only tumor associated with a significantly increased risk (HR = 3.76 95% Cl = 1.71, 8.28). However, after exclusion of patients who had had suspicious lesions before exposure the hazard ratio fell to 2.32 (95% Cl = 0.89, 6.07). 

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterised by extreme pruritus and lichenified papules and plaques that may begin in or persist in to adulthood. Topical corticosteroids are first-line prescription therapy for AD they are efficacious and have a well established safety profile. The topical calcineurin inhibitors tacrolimus and pimecrolimus have been approved as second-line topical therapy for AD. The current review evaluates the available studies on the comparative effectiveness, safety, cost, and impact on quality of life of topical corticosteroids and topical calcineurin inhibitors for the treatment of adult AD [17 ]. 

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