Calcipotriol/betamethasone dipropionate

Calcipotriol/betamethasone dipropionate
Combination of
Calcipotriol Vitamin D3 analog
Betamethasone dipropionate Corticosteroid
Clinical data
Trade names Daivobet, Dovobet, Enstilar, Taclonex, Xamiol
AHFS/Drugs.com Professional Drug Facts
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Topical (foam, gel, ointment)
Legal status
Legal status
Identifiers
ATC code D05AX52 (WHO)
PubChem CID 9832804
KEGG D10534

Calcipotriol/betamethasone dipropionate (INNs; trade name Daivobet, Enstilar, among others) is a fixed combination of the synthetic vitamin D3 analog calcipotriol (also known as calcipotriene) and the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis in adults. It is used in the form of foams, gels, and ointments.

Medical uses

Calcipotriol/betamethasone dipropionate is a topical medication for the treatment of trunk, limb, scalp and/or nail plaque psoriasis.[1][2] This medication is available in ointment, gel, or foam, formulations.[2][3] The ointment formulation was FDA approved in 2004 and is indicated for the once daily topical treatment of plaque-type psoriasis vulgaris amenable to topical therapy.[4] The foam formulation was approved by the FDA in 2015 and is indicated for the topical treatment of plaque psoriasis in patients 18 years of age and older.[3]

Contraindications

Calcipotriol/betamethasone dipropionate is contraindicated in patients with hypersensitivity to either glucocorticoids or vitamin D or disorders in calcium metabolism. This drug is also contraindicated for patients with erythrodermic, exfoliative, or pustular psoriasis.[5]

Adverse effects

Adverse events during treatment with the foam formulation have been evaluated in three 4-week randomized, multicenter, prospective vehicle- and/or active-controlled clinical trials of subjects with plaque psoriasis. The median weekly dose was 24.8 g. Application site irritation, application site pruritus (itching), folliculitis (inflammation of hair follicles), skin hypopigmentation (loss of skin color), hypercalcemia (increased blood calcium levels), urticaria, and exacerbation of psoriasis were reported in <1% of subjects. Local long-term adverse effects of continuous steroid exposure may include skin atrophy, stretch marks, telangiectasia (spider veins), dryness, local infections, and miliaria ("prickly heat").[4]

Pharmacology

Pharmacodynamics

A number of clinical studies have been conducted to research possible adverse effects of this drug combination, which can be expected from experiences with corticosteroids and vitamin D analogs.

Hypothalamic-pituitary-adrenal axis suppression

Potential effects on hypothalamic-pituitary-adrenal (HPA axis) function of the foam formulation were evaluated in a clinical trial of adults (N=35) with moderate to severe plaque psoriasis covering a mean of 18% of the body surface area of the trunk and limbs and 50% of the scalp.[6] The foam was applied once daily to all lesions on the trunk, limbs and scalp for 4 weeks. Mean (range) weekly exposure was 62 (13.5–113) g. After 4 weeks, no patient exhibited adrenal suppression, defined as a cortisol level ≤497 nmol/L 30 minutes after adrenocorticotropic hormone challenge. Lack of adrenal suppression over the course of four weeks does not preclude the possibility of HPA axis suppression during prolonged exposure.

Effects on calcium metabolism

Potential effects on calcium metabolism have been evaluated in three randomized, multicenter, prospective, vehicle- and/or active-controlled trials of the foam formulation enrolling 564 adults with plaque psoriasis. The foam was applied once daily for four weeks. In these trials, three subjects had serum calcium levels elevated above the upper limit of normal. Urinary calcium elevations above normal were reported in 17 subjects.[3]

In a published multicenter, open-label, single-arm trial of the foam formulation, 35 adults with plaque psoriasis applied the foam once daily to all lesions on the trunk, limbs, and scalp for four weeks.[6] No elevations of serum calcium, urinary calcium, or the ratio of urinary calcium to creatinine above the upper limit of normal were observed.

History

The foam formulation was approved in October 2015 by the US Food and Drug Administration.[3][7]

References

  1. ↑ Saraceno R, Gramiccia T, Frascione P, Chimenti S (Oct 2009). "Calcipotriene/betamethasone in the treatment of psoriasis: a review article". review. Expert Opinion on Pharmacotherapy 10 (14): 2357–65. doi:10.1517/14656560903198960. PMID 19663634.
  2. 1 2 McCormack PL (Dec 2011). "Spotlight on calcipotriene/betamethasone dipropionate in psoriasis vulgaris of the trunk, limbs, and scalp". review. American Journal of Clinical Dermatology 12 (6): 421–4. doi:10.2165/11207670-000000000-00000. PMID 21967117.
  3. 1 2 3 4 "Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information" (PDF). Parsippany, NJ: LEO Pharma Inc. 2015.
  4. 1 2 Daivobet® 50/500 ointment package insert 29 April 2011
  5. ↑ "Calcipotriene/Betamethasone Dipropionate (Professional Patient Advice)". Drugs.com.
  6. 1 2 Taraska V, Tuppal R, Olesen M, Bang Pedersen C, Papp K (Jul 2015). "A Novel Aerosol Foam Formulation of Calcipotriol and Betamethasone Has No Impact on HPA Axis and Calcium Homeostasis in Patients With Extensive Psoriasis Vulgaris". Journal of Cutaneous Medicine and Surgery. doi:10.1177/1203475415597094. PMID 26224733.
  7. ↑ Office of Medical Products and Tobacco Center for Drug Evaluation and Research Office of Generic Drugs (October 2015). "Approved Drug Products with Therapeutic Equivalence Evaluations" (PDF) (Supplement 10) (35th ed.). United States Food and Drug Administration, Department of Health and Human Services: 11.

Further reading

  • Kircik LH, Kumar S (Aug 2010). "Scalp psoriasis". review. Journal of Drugs in Dermatology 9 (8 Suppl ODAC Conf Pt 2): s101–5. PMID 20715392. 
  • Menter MA, Caveney SW, Gottschalk RW (Nov 2012). "Impact of clobetasol propionate 0.05% spray on health-related quality of life in patients with plaque psoriasis". review. Journal of Drugs in Dermatology 11 (11): 1348–54. PMID 23135087. 
  • Osier E, Gomez B, Eichenfield LF (Jul 2015). "Adolescent Scalp Psoriasis: Update on Topical Combination Therapy". review. The Journal of Clinical and Aesthetic Dermatology 8 (7): 43–7. PMC 4509585. PMID 26203320. 
  • Daudén E, Bewley A, Lambert J, Girolomoni G, Cambazard F, Reich K (May 2014). "Expert recommendations: the use of the fixed combination calcipotriol and betamethasone dipropionate gel for the topical treatment of psoriasis". review. Journal of the European Academy of Dermatology and Venereology. 28 Suppl 2: 22–32. doi:10.1111/jdv.12443. PMID 24684740. 
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