Pimecrolimus
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Clinical data | |
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Trade names | Elidel |
AHFS/Drugs.com | Monograph |
Pregnancy category | |
Routes of administration | topical |
ATC code | D11AH02 (WHO) |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | low systemic absorption |
Protein binding | 74%–87% |
Metabolism | Hepatic CYP3A |
Identifiers | |
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CAS Number |
137071-32-0 ![]() |
PubChem (CID) | 16051947 |
DrugBank |
DB00337 ![]() |
ChemSpider |
10482089 ![]() |
UNII |
7KYV510875 ![]() |
ChEMBL |
CHEMBL1200686 ![]() |
ECHA InfoCard | 100.124.895 |
Chemical and physical data | |
Formula | C43H68ClNO11 |
Molar mass | 810.453 g/mol |
3D model (Jmol) | Interactive image |
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Pimecrolimus is an immunomodulating agent used in the treatment of atopic dermatitis (eczema). It is available as a topical cream, once marketed by Novartis (however, Galderma has been promoting the compound in Canada since early 2007) under the trade name Elidel.
Pharmacology
Pimecrolimus is an ascomycin macrolactam derivative. It has been shown in vitro that pimecrolimus binds to macrophilin-12 (also referred to as FKBP-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.[1] Pimecrolimus has a similar mode of action to that of tacrolimus but is more selective, with no effect on dendritic (Langerhans) cells.[2] It has lower permeation through the skin than topical steroids or topical tacrolimus[3] 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.[4] It has been proven to be effective in various inflammatory skin diseases, e.g., seborrheic dermatitis,[5] cutaneous lupus erythematosus,[6] oral lichen planus,[7] vitiligo,[8] and psoriasis.[9][10] Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants.[11]
Side effects
See also: Immunosuppressants in the treatment of dermatitis
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.[12]
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.[13] Another recent review of evidence concluded that postmarketing surveillance shows no evidence for this systemic immunosuppression or increased risk for any malignancy.[14] However, there are still some strong debates and controversies 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]
References
- ↑ 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". Arch Dis Child. 88 (11): 969–973. doi:10.1136/adc.88.11.969. PMC 1719352
. PMID 14612358.
- ↑ Meingassner JG, Kowalsky E, Schwendinger H, Elbe-Bürger A, Stütz A (2003). "Pimecrolimus does not affect Langerhans cells in murine epidermis". Br J Dermatol. 149 (4): 853–857. doi:10.1046/j.1365-2133.2003.05559.x. PMID 14616380.
- ↑ Billich A, Aschauer H, Aszódi A, Stuetz A (2004). "Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus". Int J Pharm. 269 (1): 29–35. doi:10.1016/j.ijpharm.2003.07.013. PMID 14698574.
- ↑ Firooz A, Solhpour A, Gorouhi F, Daneshpazhooh M, Balighi K, Farsinejad K, Rashighi-Firoozabadi M, Dowlati Y (2006). "Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment of facial seborrheic dermatitis: a randomized, investigator-blind, clinical trial". Archives of Dermatology. 142 (8): 1066–1067. doi:10.1001/archderm.142.8.1066. PMID 16924062.
- ↑ Firooz A, Solhpour A, Gorouhi F, Daneshpazhooh M, Balighi K, Farsinejad K, Rashighi-Firoozabadi M, Dowlati Y (2006). "Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment of facial seborrheic dermatitis: a randomized, investigator-blind, clinical trial". Archives of Dermatology. 142 (8): 1066–1067. doi:10.1001/archderm.142.8.1066. PMID 16924062.
- ↑ Kreuter A, Gambichler T, Breuckmann F, Pawlak FM, Stücker M, Bader A, Altmeyer P, Freitag M (2004). "Pimecrolimus 1% cream for cutaneous lupus erythematosus". J Am Acad Dermatol. 51 (3): 407–410. doi:10.1016/j.jaad.2004.01.044. PMID 15337984.
- ↑ Gorouhi F, Solhpour A, Beitollahi JM, Afshar S, Davari P, Hashemi P, Nassiri Kashani M, Firooz A (2007). "Randomized trial of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus". J Am Acad Dermatol. 57 (5): 806–813. doi:10.1016/j.jaad.2007.06.022. PMID 17658663.
- ↑ Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert JM (2007). "Topical pimecrolimus in the treatment of vitiligo". Eur J Dermatol. 17 (1): 55–61. doi:10.1684/ejd.2007.0093. PMID 17324829.
- ↑ Kreuter A, Sommer A, Hyun J, Bräutigam M, Brockmeyer NH, Altmeyer P, Gambichler T (2006). "1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study". Arch Dermatol. 142 (9): 1138–1143. doi:10.1001/archderm.142.9.1138. PMID 16983001.
- ↑ Jacobi A, Braeutigam M, Mahler V, Schultz E, Hertl M (2008). "Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study". Dermatology. 216 (2): 133–136. doi:10.1159/000111510. PMID 18216475.
- ↑ Scheinfeld N (2004). "The use of topical tacrolimus and pimecrolimus to treat psoriasis: a review". Dermatol. Online J. 10 (1): 3. PMID 15347485.
- ↑ N H Cox & Catherine H Smith (December 2002). "Advice to dermatologists re topical tacrolimus" (DOC). Therapy Guidelines Committee. British Association of Dermatologists.
- ↑ Berger TG, Duvic M, Van Voorhees AS, VanBeek MJ, Frieden IJ; American Academy of Dermatology Association Task Force (2006). "The use of topical calcineurin inhibitors in dermatology: safety concerns Report of the American Academy of Dermatology Association Task Force". J Am Acad Dermatol. 54 (5): 818–823. doi:10.1016/j.jaad.2006.01.054. PMID 16635663.
- ↑ Spergel JM, Leung DY (2006). "Safety of topical calcineurin inhibitors in atopic dermatitis: evaluation of the evidence". Curr Allergy Asthma Rep. 6 (4): 270–274. doi:10.1007/s11882-006-0059-7. PMID 16822378.
- ↑ Stern RS (2006). "Topical calcineurin inhibitors labeling: putting the "box" in perspective". Archives of Dermatology. 142 (9): 1233–1235. doi:10.1001/archderm.142.9.1233. PMID 16983018.
- ↑ "Statement Regarding FDA Decision On Two Eczema Medications By American Academy Of Dermatology".
- ↑
External links
- Elidel official homepage
- FDA News
- NPS RADAR
- Article about American Academy of Dermatology speaking out against black box warning
- Report of the Calcineurin Task Force of the ACAAI and AAAAI