IUPAC_name = (3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)
-3-{(E)-2- [(1R,3R,4S)-4-Chloro-3
-methoxycyclohexyl] -1-methylvinyl}
-3H-pyrido [2,1-c] [1,4] oxaazacyclotricosine

width = 250

CAS_number = 137071-32-0
ATC_prefix = D11
ATC_suffix = AX15
PubChem = 6447131
DrugBank = APRD01182
C = 43 | H = 68 | Cl = 1 | N = 1 | O = 11
molecular_weight = 810.453 g/mol
bioavailability = low systemic absorption
protein_bound =74%–87%
metabolism = Hepatic CYP3A
elimination_half-life =
excretion =
pregnancy_US = C
legal_US = Rx-only
routes_of_administration = topical

Pimecrolimus is an immunomodulating agent used in the treatment of atopic dermatitis (eczema). It is currently available as a topical cream, once marketed by Novartis, (however Galderma will be promoting the molecule in Canada in early 2007) under the trade name Elidel.


Pimecrolimus is an ascomycin macrolactam derivative. It has been shown "in vitro" that pimecrolimus binds to macrophilin-12 and inhibits calcineurin. Thus pimecrolimus inhibits T-cell activation by inhibiting the synthesis and release of cytokines from T-cells. Pimecrolimus also prevents the release of inflammatory cytokines and mediators from mast cells.

General characteristics

Pimecrolimus, like tacrolimus, belongs to the ascomycin class of macrolactam immunosuppressives, acting by the inhibition of T-cell activation by the calcineurin pathway and inhibition of the release of numerous inflammatory cytokines, thereby preventing the cascade of immune and inflammatory signals. [cite article |author= Allen BR, Lakhanpaul M, Morris A, Lateo S, Davies T, Scott G, Cardno M, Ebelin ME, Burtin P, Stephenson TJ |title= Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients |journal= Arch Dis Child |year=2003 |volume=88 |issue=11 |pages=969-973 |pmid=14612358 |url=http://www.ncbi.nlm.nih.gov/pubmed/14612358] Pimecrolimus has a similar mode of action to that of tacrolimus but is more selective, with no effect on dendritic (Langerhans) cells. [cite article |author= Meingassner JG, Kowalsky E, Schwendinger H, Elbe-Bürger A, Stütz A |title= Pimecrolimus does not affect Langerhans cells in murine epidermis |journal= Br J Dermatol |year=2003 |volume=149 |issue=4 |pages=853-857 |pmid=14616380 |url=http://www.ncbi.nlm.nih.gov/pubmed/14616380] It has lower permeation through the skin than topical steroids or topical tacrolimus [cite article |author= Billich A, Aschauer H, Aszódi A, Stuetz A |title= Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus |journal=Int J Pharm |year=2004 |volume=269 |issue=1 |pages=29-35 |pmid=14698574 |url=http://www.ncbi.nlm.nih.gov/pubmed/14698574] although they have not been compared with each other for their permeation ability through mucosa. In addition, in contrast with topical steroids, pimecrolimus does not produce skin atrophy. [cite article |author= Gupta AK, Chow M |title= Pimecrolimus: a review |journal= J Eur Acad Dermatol Venereol |year=2003 |volume=17 |issue=5 |pages=493-503 |pmid=12941081 |url=http://www.ncbi.nlm.nih.gov/pubmed/12941081]

Other uses

Due to its immunosuppressive properties it is also being evaluated as the anti-proliferative agent for drug-eluting stents.

Dermatologic indications

Pimecrolimus 1% cream has been approved by the Food and Drug Administration(FDA) for the treatment of atopic dermatitis. It has been proven to be effective in various inflammatory skin diseases, eg, seborrheic dermatitis, cite journal |author= Firooz A, Solhpour A, Gorouhi F, Daneshpazhooh M, Balighi K, Farsinejad K, Rashighi-Firoozabadi M, Dowlati Y |title= Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment of facial seborrheic dermatitis: a randomized, investigator-blind, clinical trial |journal=Archives of Dermatology |volume=142 |issue= 8 |pages=1066–1067 |year=2006 |pmid= 16924062 |url=http://www.ncbi.nlm.nih.gov/pubmed/16924062] cutaneous lupus erythematosus, [cite article |author= Kreuter A, Gambichler T, Breuckmann F, Pawlak FM, Stücker M, Bader A, Altmeyer P, Freitag M |title= Pimecrolimus 1% cream for cutaneous lupus erythematosus |journal= J Am Acad Dermatol |year=2004 |volume=51 |issue=3 |pages=407-410 |pmid=15337984 |url=http://www.ncbi.nlm.nih.gov/pubmed/15337984] oral lichen planus, [cite article |author= Gorouhi F, Solhpour A, Beitollahi JM, Afshar S, Davari P, Hashemi P, Nassiri Kashani M, Firooz A |title=Randomized trial of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus |journal= J Am Acad Dermatol |year=2007 |volume=57 |issue=5 |pages=806-813 |pmid=17658663 |url=http://www.ncbi.nlm.nih.gov/pubmed/17658663] vitiligo, [cite article |author= Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert JM |title=Topical pimecrolimus in the treatment of vitiligo |journal= Eur J Dermatol |year=2007 |volume=17 |issue=1 |pages=55-61 |pmid=17081269 |url=http://www.ncbi.nlm.nih.gov/pubmed/17081269] and psoriasis. [cite article |author= Kreuter A, Sommer A, Hyun J, Bräutigam M, Brockmeyer NH, Altmeyer P, Gambichler T |title=1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study |journal= Arch Dermatol |year=2006 |volume=142 |issue=9 |pages=1138-1143 |pmid=16983001|url=http://www.ncbi.nlm.nih.gov/pubmed/16983001] , [cite article |author= Jacobi A, Braeutigam M, Mahler V, Schultz E, Hertl M |title=Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study |journal= Dermatology |year=2008 |volume=216 |issue=2 |pages=133-136 |pmid=18216475 |url=http://www.ncbi.nlm.nih.gov/pubmed/18216475]

ide effects

"See also: Immunomodulators in the treatment of eczema"

In January 2006, the United States Food and Drug Administration (FDA) announced that Elidel packaging would be required to carry a black box warning regarding the potential increased risk of lymph node or skin malignancy, as for the similar drug tacrolimus. Whereas current practice by UK dermatologists is not to consider this a significant real concern and they are increasingly recommending the use of such new drugs. cite web | author= N H Cox and Catherine H Smith | year = 2002 | month = December | url=http://www.bad.org.uk/healthcare/guidelines/Advice_re_topical_tacrolimus.doc | title =Advice to dermatologists re topical tacrolimus | format =DOC | work = Therapy Guidelines Committee | publisher = British Association of Dermatologists]

Importantly, although the FDA has approved updated black-box warning for tacrolimus and pimecrolimus, the recent report of the American Academy of Dermatology Association Task Force finds that there is no causal proof that topical immunomodulators cause lymphoma or nonmelanoma skin cancer, and systemic immunosuppression after short-term or intermittent long-term topical application seems an unlikely mechanism. [cite article |author= Berger TG, Duvic M, Van Voorhees AS, VanBeek MJ, Frieden IJ; American Academy of Dermatology Association Task Force |title=The use of topical calcineurin inhibitors in dermatology: safety concerns Report of the American Academy of Dermatology Association Task Force |journal= J Am Acad Dermatol |year=2006 |volume=54|pages=818-823 |url=http://www.ncbi.nlm.nih.gov/pubmed/16635663] Another recent review of evidence concluded that postmarketing surveillance shows no evidence for this systemic immunosuppression or increased risk for any malignancy. cite article |author= Stern RS |title= Topical calcineurin inhibitors labeling: putting the "box" in perspective |journal=Archives of Dermatology |year=2006 |volume=142 |pages=1233-1235 |pmid=16983018 |url=http://www.ncbi.nlm.nih.gov/pubmed/16983018] Dermatologists' and Allergists' professional societies, the American Academy of Dermatology [http://www.medicalnewstoday.com/articles/21091.php] , and the American Academy of Allergy, Asthma, and Immunology, have protested the inclusion of the black box warning. The AAAAI states "None of the information provided for the cases of lymphoma associated with the use of topical pimecrolimus or tacrolimus in AD indicate or suggest a causal relationship." [http://www.aaaai.org/members/resources/calcineurin_task_force.pdf] .
Topical corticosteroids can cause different types of systemic and local adverse effects. Systemic adverse events consist of glaucoma (in periorbital application), cataract, iatrogenic Cushing syndrome, retarded growth, and Addison crises, hyperglycemia and diabetes mellitus, osteopathy/osteoporosis, hypertension, peptic ulcer, and hypocalcemia. Local side effects encompass atrophic changes (e.g. skin atrophy, telangiectasia, striae, purpura, stellate pseudoscars, ulceration, and easy bruising), Infections (e.g. masked microbial infections, cutaneous candidiasis, herpes, or demodex aggravation, Kaposi sarcoma reactivation, granuloma gluteale infantum, Steroid acne, perioral dermatitis, allergic contact dermatitis, steroid rosacea, hirsutism, hyperpigmentation, hypopigmentation, photosensitization, psoriasis rebound flare, and epidermal barrier disturbance, hypertrichosis, delayed wound healing and aged-like effect on skin. [cite article |author= Brazzini B, Pimpinelli N |title=New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use |journal= Am J Clin Dermatol |year=2002 |volume=3 |issue=1 |pages=47-58 |pmid=11817968 |url=http://www.ncbi.nlm.nih.gov/pubmed/11817968] , [cite article |author= Hengge UR, et al |title=Adverse effects of topical glucocorticosteroids |journal= J Am Acad Dermatol |year=2006 |volume=54 |issue=1 |pages=1-15 |pmid= 16384751 |url=http://www.ncbi.nlm.nih.gov/pubmed/16384751] In light of the known side effects of steroids which are used first line for many dermatological conditions, many doctors prefer to use this drug instead. In practice, other doctors use the drug as a second-line remedy only after conventional methods of treatment have failed.


External links

* [http://www.elidel.com Elidel] official homepage
* [http://www.fda.gov/bbs/topics/news/2006/NEW01299.html FDA News]
* [http://www.npsradar.org.au/site.php?page=1&content=/npsradar/content/pimecrolimus.html NPS RADAR]
* [http://www.protopiclawyers.com Offers more information on possible cancer risks of Elidel (Pimecrolimus)]
* [http://www.medicalnewstoday.com/articles/21091.php Article about American Academy of Dermatology speaking out against black box warning]
* [http://www.aaaai.org/members/resources/calcineurin_task_force.pdf Report of the Calcineurin Task Force of the ACAAI and AAAAI]

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