Pimecrolimus

Source: Wikipedia, the free encyclopedia.
Pimecrolimus
Clinical data
Trade namesElidel
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B3
immunosuppressant
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilitylow systemic absorption
Protein binding74%–87%
MetabolismHepatic CYP3A
Identifiers
  • (3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-3-{(E)-2-[(1R,3R,4S)-4-chloro-3-methoxycyclohexyl]-1-methylvinyl}-8-ethyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-14,16-dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosin-1,7,20,21(4H,23H)-tetrone
JSmol)
  • Cl[C@@H]1CC[C@H](C[C@H]1OC)\C=C(/C)[C@H]2OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@]3(O)O[C@H]([C@H](C[C@@H](C)CC(\C)=C\[C@@H](CC)C(=O)C[C@H](O)[C@H]2C)OC)[C@@H](OC)C[C@H]3C
  • InChI=1S/C43H68ClNO11/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)45-16-12-11-13-32(45)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-31(44)35(22-29)52-7/h18,20,25,27-33,35-39,46,51H,10-17,19,21-23H2,1-9H3/b24-18+,26-20+/t25-,27+,28+,29-,30+,31+,32-,33-,35+,36-,37-,38+,39+,43+/m0/s1 checkY
  • Key:KASDHRXLYQOAKZ-ZPSXYTITSA-N checkY
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Pimecrolimus is an

calcineurin inhibitor class used in the treatment of atopic dermatitis
(eczema).

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

Medical uses

It has been proven to be effective in various

seborrheic dermatitis,[2]
cutaneous lupus erythematosus,[3]
oral lichen planus,[4]
vitiligo,[5] and psoriasis.[6][7] Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants.[8]

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.[9][10]

Side effects

See also: Immunosuppressants in the treatment of dermatitis

In January 2006, the United States

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.[11]

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.[12] Another recent review of evidence concluded that postmarketing surveillance shows no evidence for this systemic immunosuppression or increased risk for any malignancy.[13]

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.[14]
However, strong debates and controversies continue regarding the exact indications of immunomodulators and their duration of use in the absence of active controlled trials.[15] Dermatologists' and allergists' professional societies, the American Academy of Dermatology,[16] 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."[17]

Pharmacology

Pimecrolimus is an

cytokines from T-cells. Pimecrolimus also prevents the release of inflammatory cytokines and mediators from mast cells.[citation needed
]

Pimecrolimus, like

cytokines, thereby preventing the cascade of immune and inflammatory signals.[18]
Pimecrolimus has a similar mode of action to that of tacrolimus but is more selective, with no effect on dendritic (Langerhans) cells.[19] It has lower permeation through the skin than topical steroids or topical tacrolimus[20] 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.[21]

Development and Production

Pimecrolimus was developed by Novartis. Its development number was ascomycin derivative ASM 981.[22]

The NDA was filed December 15, 2000. It received US FDA approval on December 13, 2001.[23] At its US approval, it was one of the first new eczema treatments introduced since the topical corticosteroids of the 1950s.[24] It is available as a topical cream, once marketed by . Since early 2007, Galderma has been promoting the compound in Canada. The trade name is Elidel.

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. PMID 16924062
    .
  3. PMID 15337984
    .
  4. PMID 17658663
    .
  5. PMID 17324829.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link
    )
  6. PMID 16983001
    .
  7. S2CID 35741213
    .
  8. PMID 15347485
    .
  9. PMID 26132597
    .
  10. S2CID 253470127
    .
  11. ^ Cox NH, Smith CH (December 2002). "Advice to dermatologists re topical tacrolimus". Therapy Guidelines Committee. British Association of Dermatologists. Archived from the original (DOC) on 2006-05-25.
  12. PMID 16635663
    .
  13. S2CID 40761750
    .
  14. S2CID 253470127
    .
  15. PMID 16983018
    .
  16. ^ "Statement Regarding FDA Decision On Two Eczema Medications By American Academy Of Dermatology". Archived from the original on 2008-04-07. Retrieved 2007-09-24.
  17. PMID 15940142
    .
  18. PMID 14612358
    .
  19. S2CID 26517363
    .
  20. PMID 14698574
    .
  21. S2CID 34706897
    .
  22. PMID 11907497
    .
  23. ^ "Application No.: 21-302 Elidel (Pimecrolimus) Cream". US DHHS. Retrieved 11 April 2024.
  24. ^ "US SEC FORM 20-F NOVARTIS AG filed January 31, 2007" (PDF). www.novartis.com. NOVARTIS Inc. 31 January 2007. Retrieved 11 April 2024.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Pimecrolimus&oldid=1218592525"