Calcipotriol

Calcipotriol
Names
Trade namesDaivonex, Dovonex, Sorilux, others
Other namescalcipotriene (USAN US)
IUPAC name
  • (1R,3S,5E)-5-{2-[(1R,3aS,4Z,7aR)-1-[(2R,3E)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
Clinical data
Drug classForm of vitamin D[1]
Main usesPsoriasis.[2]
Side effectsSkin irritation, itchiness, worsening psoriasis[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    use    		Topical
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa608018
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability5 to 6%
    MetabolismLiver
    ExcretionBiliary
    Chemical and physical data
    FormulaC27H40O3
    Molar mass412.614 g·mol−1
    3D model (JSmol)
    SMILES
    • O[C@@H]1CC(\C(=C)[C@@H](O)C1)=C\C=C2/CCC[C@]4([C@H]2CC[C@@H]4[C@@H](/C=C/[C@@H](O)C3CC3)C)C
    InChI
    • InChI=1S/C27H40O3/c1-17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-26,28-30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,25-,26+,27-/m1/s1 checkY
    • Key:LWQQLNNNIPYSNX-UROSTWAQSA-N checkY

    Calcipotriol, also known as calcipotriene, is a medication used to treat psoriasis.[2] It is applied to the skin.[2] It is also available in combination with betamethasone.[2]

    Common side effects include skin irritation, itchiness, and worsening psoriasis.[2] Other side effects may include increased sensitivity to UV radiation and high calcium.[2] Safety in pregnancy is unclear.[2] It is a manufactured derivative of calcitriol, a form of vitamin D.[1]

    Calcipotriol was patented in 1985 and approved for medical use in 1991.[3] It is on the World Health Organization's List of Essential Medicines.[4] It is available as a generic medication.[5] In the United States 60 grams costs about 70 USD as of 2021.[5]

    Medical uses

    Chronic plaque psoriasis is the chief medical use of calcipotriol.[6] It has also been used successfully in the treatment of alopecia areata.[7]

    • Psoriasis pre-calcipotriol
      Psoriasis pre-calcipotriol
    • Psoriasis post-calcipotriol
      Psoriasis post-calcipotriol

    Contraindications

    Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol use.[8]

    Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity.[8]

    Side effects

    Side effects by frequency:[6][8][9][10]

    Very common (> 10% frequency)
    • Burning
    • Itchiness
    • Skin irritation
    Common (1–10% frequency)
    Uncommon (0.1–1% frequency)
    Rare (< 0.1% frequency)

    Interactions

    No drug interactions are known.[8]

    Pharmacology

    Mechanism of action

    The efficacy of calcipotriol in the treatment of psoriasis was first noticed by the observation of patients receiving various forms of vitamin D in an osteoporosis study. Unexpectedly, some patients who also suffered from psoriasis experienced dramatic reductions in lesion counts.[11]

    The precise mechanism of calcipotriol in remitting psoriasis is not well understood. However, it has been shown to have comparable affinity with calcitriol for the vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. The vitamin D receptor belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kidney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes.

    In mouse studies, topical calcipotriol administration to the ear and dorsal skin led to a dose-dependent increase in the production of the epithelial cell-derived cytokine TSLP by keratinocytes, and triggered atopic dermatitis at high concentrations.[12] This upregulation of TSLP production due to calcipotriol application is thought to be mediated through the coactivation of vitamin D receptor/RXRα and vitamin D receptor/RXRβ heterodimers. As psoriasis is typically thought to be partially driven by Th1/Th17 inflammatory cytokines,[13] calcipotriol treatment at appropriate concentrations may alleviate psoriasis symptoms by repressing Th1/Th17 inflammation through TSLP production, which is linked to a Th2 response. However, it is important to note that this has not yet been confirmed.

    Pharmacokinetics

    After application and systemic uptake, calcipotriol undergoes rapid liver metabolism. Calcipotriol is metabolized to MC1046 (the α,β−unsaturated ketone analog), which is subsequently metabolized to its primary metabolite, the saturated ketone analog MC1080. MC1080 is then slowly metabolized to calcitroic acid.[14]

    The metabolites of calcipotriol are less potent than the parent compound.

    Chemistry

    Calcipotriol is a white to almost white crystalline compound.

    Society and culture

    It is marketed under the trade name "Dovonex" in the United States, "Daivonex" outside North America, and "Psorcutan" in Germany.

    References

    1. 1 2 "Calcipotriol". SPS - Specialist Pharmacy Service. 28 April 2015. Archived from the original on 11 October 2021. Retrieved 29 December 2021.
    2. 1 2 3 4 5 6 7 8 "Calcipotriene Monograph for Professionals". Drugs.com. Archived from the original on 26 July 2017. Retrieved 29 December 2021.
    3. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 452. ISBN 9783527607495. Archived from the original on 2021-01-22. Retrieved 2021-03-03.
    4. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
    5. 1 2 "Calcipotriene Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 25 October 2016. Retrieved 29 December 2021.
    6. 1 2 Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
    7. ↑ Kim DH, Lee JW, Kim IS, Choi SY, Lim YY, Kim HM, et al. (August 2012). "Successful treatment of alopecia areata with topical calcipotriol". Annals of Dermatology. 24 (3): 341–4. doi:10.5021/ad.2012.24.3.341. PMC 3412244. PMID 22879719.
    8. 1 2 3 4 "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 2 February 2014. Retrieved 26 January 2014.
    9. ↑ "CALCIPOTRIENE (calcipotriene) solution [E. FOUGERA & CO. A division of Fougera Pharmaceuticals Inc.]". DailyMed. E. FOUGERA & CO. A division of Fougera Pharmaceuticals Inc. May 2012. Archived from the original on 2 February 2014. Retrieved 26 January 2014.
    10. ↑ "PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g" (PDF). TGA eBusiness Services. LEO Pharma Pty Ltd. 28 April 2011. Archived from the original on 23 February 2017. Retrieved 26 January 2014.
    11. ↑ Morimoto S, Kumahara Y (March 1985). "A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3". Medical Journal of Osaka University. 35 (3–4): 51–4. PMID 4069059.
    12. ↑ Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P (August 2006). "Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis". Proceedings of the National Academy of Sciences of the United States of America. 103 (31): 11736–41. doi:10.1073/pnas.0604575103. PMC 1544239. PMID 16880407.
    13. ↑ Wong T, Hsu L, Liao W (2013-02-01). "Phototherapy in psoriasis: a review of mechanisms of action". Journal of Cutaneous Medicine and Surgery. 17 (1): 6–12. doi:10.2310/7750.2012.11124. PMC 3736829. PMID 23364144.
    14. ↑ "Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information" (PDF). Parsippany, NJ: LEO Pharma Inc. 2015. Archived from the original (PDF) on 2018-09-20. Retrieved 2021-03-03.
    Identifiers:
    • "Calcipotriene". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2021-02-25. Retrieved 2021-03-03.
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