What is calcipotriene?

What is Calcipotriene?

Calcipotriene (also known as calcipotriol) is a synthetic vitamin D3 analogue used topically to treat psoriasis by binding to vitamin D receptors, which inhibits keratinocyte proliferation and enhances keratinocyte differentiation, thereby normalizing the accelerated cell turnover characteristic of psoriatic skin. 1, 2

Chemical Structure and Formulation

• Calcipotriene is chemically designated as 24-cyclopropyl-(1α,3β,5Z,7E,22E,24S)-9,10-Secochola-5,7,10(19),22-tetraene-1,3,24-triol with molecular formula C27H40O3 and molecular weight of 412.62 3
• It is available in multiple formulations in the United States including ointment (0.005%), foam, cream, solution, and in fixed-dose combination with betamethasone dipropionate 1, 3

Mechanism of Action

Calcipotriene works through two complementary mechanisms:

• Inhibits keratinocyte proliferation and DNA synthesis in psoriatic plaques, addressing the hyperproliferative state of psoriatic skin 2
• Promotes keratinocyte differentiation, helping normalize the accelerated cell turnover seen in psoriasis 1, 2
• At the molecular level, it modulates immune responses by increasing interleukin-10 (anti-inflammatory) and decreasing interleukin-8 (pro-inflammatory) levels within lesions 4

Clinical Efficacy

Treatment outcomes are time-dependent, with full therapeutic effect requiring 8 weeks:

• 65-70% of patients experience marked improvement or clearing with calcipotriene monotherapy 2, 5
• Efficacy is limited at 4 weeks but becomes significant at 8 weeks 1, 2
• For scalp psoriasis specifically, calcipotriene foam achieved clear or almost clear status in 40.9% versus 24.2% with vehicle after 8 weeks 1, 6

Combination therapy with betamethasone dipropionate demonstrates superior efficacy:

• 69-74% achieve clear or almost clear status in 52-week studies versus 27% with vehicle 2
• This combination is more effective than either agent alone and is recommended as first-line topical treatment by American and European guidelines 1, 7

Pharmacokinetics

• Approximately 6% (±3%) of applied calcipotriene is absorbed systemically when applied to psoriatic plaques, or 5% (±2.6%) on normal skin 3
• Absorbed drug is rapidly converted to inactive metabolites within 24 hours of application 3
• Metabolism follows a similar pathway to natural vitamin D, with excretion via bile 3

Dosing and Administration

Standard dosing regimen:

• Apply twice daily to affected areas for 8 weeks 2, 8
• Maximum weekly dose: 100g/week for adults to prevent hypercalcemia 2, 9
• Pediatric dosing: limited to 50g/week/m² for calcipotriol to prevent hypercalcemia 2, 9

For combination therapy with betamethasone dipropionate:

• Apply once daily (more convenient than twice-daily monotherapy) 2
• Can be used for up to 52 weeks for long-term management 9

Safety Profile

Calcipotriene has an excellent safety profile with minimal systemic effects:

• At recommended doses, systemic effects on calcium metabolism are rare 2
• No serious adverse events including hypothalamic-pituitary-adrenal axis suppression observed in 52-week studies 6
• Most adverse events are mild, transient local reactions occurring in approximately 1-2% of subjects 8
• Unlike topical corticosteroids, calcipotriene does not cause skin atrophy or striae 10

Use with caution in:

• Patients with disorders of calcium metabolism 2, 6
• Patients with renal disease 2, 6

Critical Drug Interactions and Application Pitfalls

Never combine calcipotriene with salicylic acid - the acidic pH inactivates calcipotriene and eliminates its effectiveness 2, 6

Phototherapy considerations:

• Apply calcipotriene after UV treatment, as UVA radiation decreases calcipotriene concentration on the skin 2, 6
• Thick layers can block UVB radiation, potentially increasing the minimal erythema dose 9

Special Indications

Facial and inverse psoriasis:

• Calcipotriene combined with hydrocortisone is efficacious for facial psoriasis treatment for up to 8 weeks 1, 9
• Particularly valuable for these sensitive areas due to its corticosteroid-sparing function 2

Scalp psoriasis:

• Calcipotriene foam is specifically effective for scalp involvement 1, 6

Long-Term Management Strategy

The American Academy of Dermatology-National Psoriasis Foundation supports long-term use up to 52 weeks for mild to moderate psoriasis 9, 6

Maintenance regimen options:

• Vitamin D analogues twice daily on weekdays combined with high-potency topical corticosteroids twice daily on weekends 9
• Rotational therapy with topical calcineurin inhibitors, emollients, tar-based therapies, and topical corticosteroids as steroid-sparing regimens 9