Pimecrolimus

Overview

Pimecrolimus is an immunosuppressant drug of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema). WP

It is available as a topical cream. It was developed and formerly marketed by Novartis under the trade name Elidel. WP

Uses, dosage and effects

Medical uses

It has been proven to be effective in various inflammatory skin diseases, e.g., seborrheic dermatitis, cutaneous lupus erythematosus, oral lichen planus, vitiligo, and psoriasis. Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants.[1–7] WP

Atopic dermatitis

If topical corticosteroids and moisturisers fail in the treatment of atopic dermatitis, short-term treatment with topical calcineurin inhibitors such as tacrolimus or pimecrolimus may be tried. Both tacrolimus and pimecrolimus are effective and safe to use in AD.[8][9] WP

Risks and side effects

Side effects

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 cancer, 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.[10] WP

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. Another recent review of evidence concluded that postmarketing surveillance shows no evidence for this systemic immunosuppression or increased risk for any malignancy.[11][12] WP

A 2023 systematic review and meta-analysis published in The Lancet Child & Adolescent Health further concluded with moderate-certainty evidence that the two drugs were not associated with any increased risk of cancer. However, strong debates and controversies continue regarding the exact indications of immunomodulators and their duration of use in the absence of active controlled trials. Dermatologists' and allergists' professional societies, the American Academy of Dermatology, 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."[9][13][14][15] WP

Pharmacology

Pharmacology

Pimecrolimus is an ascomycin macrolactam derivative. It has been shown in vitro that pimecrolimus binds to FKBP1A and also 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. WP⚠ Wikipedia itself has flagged this text: citation needed.

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. Pimecrolimus has a similar mode of action to that of tacrolimus but is more selective, with no effect on dendritic (Langerhans) cells. It has lower permeation through the skin than topical steroids or topical tacrolimus 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.[16–19] WP

Chemistry

Formula

C43H68ClNO11 PC

CAS number

137071-32-0 PC

Molar mass (g/mol)

810.4 PC

IUPAC name (computed by PubChem)

(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-12-[(E)-1-[(1R,3R,4R)-4-chloro-3-methoxycyclohexyl]prop-1-en-2-yl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone PC

SMILES

CC[C@@H]1/C=C(/C[C@@H](C[C@@H]([C@@H]2[C@H](C[C@H]([C@@](O2)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@@H]([C@@H]([C@H](CC1=O)O)C)/C(=C/[C@@H]4CC[C@H]([C@@H](C4)OC)Cl)/C)O)C)OC)OC)C)\C PC

InChIKey

KASDHRXLYQOAKZ-ZPSXYTITSA-N PC

PubChem CID

16051947

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Firooz A, Solhpour A, Gorouhi F, Daneshpazhooh M, Balighi K, Farsinejad K, Rashighi-Firoozabadi M, Dowlati Y. Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment of facial seborrheic dermatitis: a randomized, investigator-blind, clinical trial. Archives of Dermatology. August 2006. doi:10.1001/archderm.142.8.1066 · PMID 16924062
2. Journal / agency Kreuter A, Gambichler T, Breuckmann F, Pawlak FM, Stücker M, Bader A, Altmeyer P, Freitag M. Pimecrolimus 1% cream for cutaneous lupus erythematosus. Journal of the American Academy of Dermatology. September 2004. doi:10.1016/j.jaad.2004.01.044 · PMID 15337984
3. Journal / agency Gorouhi F, Solhpour A, Beitollahi JM, Afshar S, Davari P, Hashemi P, Nassiri Kashani M, Firooz A. Randomized trial of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus. Journal of the American Academy of Dermatology. November 2007. doi:10.1016/j.jaad.2007.06.022 · PMID 17658663
4. Journal / agency Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert JM. Topical pimecrolimus in the treatment of vitiligo. European Journal of Dermatology. 2007. doi:10.1684/ejd.2007.0093 · PMID 17324829
5. Journal / agency Kreuter A, Sommer A, Hyun J, Bräutigam M, Brockmeyer NH, Altmeyer P, Gambichler T. 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study. Archives of Dermatology. September 2006. doi:10.1001/archderm.142.9.1138 · PMID 16983001
6. Journal / agency Jacobi A, Braeutigam M, Mahler V, Schultz E, Hertl M. Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study. Dermatology. 2008. doi:10.1159/000111510 · PMID 18216475
7. Journal / agency Scheinfeld N. The use of topical tacrolimus and pimecrolimus to treat psoriasis: a review. Dermatology Online Journal. July 2004. doi:10.5070/D35ZK7V6CS · PMID 15347485
8. Journal / agency Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM. Topical tacrolimus for atopic dermatitis. The Cochrane Database of Systematic Reviews. July 2015. doi:10.1002/14651858.CD009864.pub2 · PMID 26132597 · PMC6461158
9. Journal / agency Devasenapathy N, Chu A, Wong M, Srivastava A, Ceccacci R, Lin C, MacDonald M, Wen A, Steen J, Levine M, Pyne L, Schneider L, Chu DK. Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis. The Lancet. Child & Adolescent Health. January 2023. doi:10.1016/S2352-4642(22)00283-8 · PMID 36370744
10. Other Cox NH, Smith CH. Advice to dermatologists re topical tacrolimus. December 2002
11. Journal / agency Berger TG, Duvic M, Van Voorhees AS, VanBeek MJ, Frieden IJ. The use of topical calcineurin inhibitors in dermatology: safety concerns. Report of the American Academy of Dermatology Association Task Force. Journal of the American Academy of Dermatology. May 2006. doi:10.1016/j.jaad.2006.01.054 · PMID 16635663
12. Journal / agency Spergel JM, Leung DY. Safety of topical calcineurin inhibitors in atopic dermatitis: evaluation of the evidence. Current Allergy and Asthma Reports. July 2006. doi:10.1007/s11882-006-0059-7 · PMID 16822378
13. Journal / agency Stern RS. Topical calcineurin inhibitors labeling: putting the "box" in perspective. Archives of Dermatology. September 2006. doi:10.1001/archderm.142.9.1233 · PMID 16983018
14. Other Statement Regarding FDA Decision On Two Eczema Medications By American Academy Of Dermatology
15. Journal / agency Fonacier L, Spergel J, Charlesworth EN, Weldon D, Beltrani V, Bernhisel-Broadbent J, Boguniewicz M, Leung DY. Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology. The Journal of Allergy and Clinical Immunology. June 2005. doi:10.1016/j.jaci.2005.04.006 · PMID 15940142
16. Journal / agency Allen BR, Lakhanpaul M, Morris A, Lateo S, Davies T, Scott G, Cardno M, Ebelin ME, Burtin P, Stephenson TJ. Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients. Archives of Disease in Childhood. November 2003. doi:10.1136/adc.88.11.969 · PMID 14612358 · PMC1719352
17. Journal / agency Meingassner JG, Kowalsky E, Schwendinger H, Elbe-Bürger A, Stütz A. Pimecrolimus does not affect Langerhans cells in murine epidermis. The British Journal of Dermatology. October 2003. doi:10.1046/j.1365-2133.2003.05559.x · PMID 14616380
18. Journal / agency Billich A, Aschauer H, Aszódi A, Stuetz A. Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus. International Journal of Pharmaceutics. January 2004. doi:10.1016/j.ijpharm.2003.07.013 · PMID 14698574
19. Journal / agency Murrell DF, Calvieri S, Ortonne JP, Ho VC, Weise-Riccardi S, Barbier N, Paul CF. A randomized controlled trial of pimecrolimus cream 1% in adolescents and adults with head and neck atopic dermatitis and intolerant of, or dependent on, topical corticosteroids. The British Journal of Dermatology. November 2007. doi:10.1111/j.1365-2133.2007.08192.x · PMID 17935515

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