Calcipotriene - Drug Monograph

Introduction

Calcipotriene (also known as calcipotriol outside the United States) is a synthetic vitamin D3 analog primarily used in the treatment of plaque psoriasis. First approved by the FDA in 1993, it represents a cornerstone of topical therapy for mild to moderate psoriasis, offering patients a non-steroidal treatment option with a favorable safety profile when used appropriately.

Mechanism of Action

Calcipotriene exerts its therapeutic effects through binding to vitamin D receptors (VDRs) present on keratinocytes and immune cells. This binding modulates keratinocyte differentiation and proliferation while inhibiting T-cell activation and cytokine production. Specifically, calcipotriene:

• Reduces epidermal proliferation
• Promotes keratinocyte differentiation
• Downregulates inflammatory mediators (IL-2, IFN-γ, IL-8)
• Normalizes epidermal cell maturation

Unlike natural vitamin D, calcipotriene has minimal effects on calcium metabolism at therapeutic doses due to its rapid hepatic metabolism.

Indications

• Treatment of plaque psoriasis (vulgaris) in adults and pediatric patients aged 2 years and older

• Scalp psoriasis
• Nail psoriasis
• Vitiligo (as combination therapy)
• Other papulosquamous disorders (under specialist supervision)

Dosage and Administration

• Ointment (0.005%): Apply twice daily to affected areas
• Cream (0.005%): Apply twice daily to affected areas
• Solution (0.005%): Apply twice daily to scalp psoriasis
• Foam (0.005%): Apply twice daily to scalp and body psoriasis

• Maximum weekly dose: 100 grams (adults); 75 grams (children 12-17 years); 50 grams (children 2-11 years)
• Affected area should not exceed 30% of body surface area
• Apply thinly to affected areas only
• Wash hands after application unless hands are being treated

• Renal impairment: Use with caution; monitor calcium levels
• Hepatic impairment: No dosage adjustment required
• Elderly: Increased risk of hypercalcemia; monitor calcium levels
• Pediatrics: Safety established down to age 2 years

Pharmacokinetics

Contraindications

• Hypersensitivity to calcipotriene or any component of the formulation
• Demonstration of hypercalcemia or vitamin D toxicity
• Use on the face due to increased risk of irritation
• Patients with acute psoriatic eruptions (may worsen condition)

Warnings and Precautions

• Hypercalcemia: May occur with excessive use; monitor serum calcium if using >100g/week
• Skin irritation: May cause local irritation, erythema, burning, or itching
• Photosensitivity: Use sun protection during treatment
• Facial and intertriginous areas: Avoid application due to increased irritation risk
• Pregnancy: Category C - use only if potential benefit justifies potential risk
• Lactation: Use with caution; unknown if excreted in human milk

Drug Interactions

• Other vitamin D analogs: Increased risk of hypercalcemia
• Thiazide diuretics: May potentiate hypercalcemia
• Systemic corticosteroids: May alter calcium metabolism
• Topical agents: Avoid concurrent use with other topical medications unless directed by physician

• May falsely elevate serum calcium measurements if contamination occurs during blood draw

Adverse Effects

• Local irritation (burning, itching, stinging)
• Erythema
• Dry skin
• Skin peeling
• Dermatitis

• Worsening of psoriasis
• Skin atrophy
• Pigmentation changes
• Photosensitivity reactions

• Hypercalcemia (with excessive use)
• Allergic contact dermatitis
• Facial and periorbital edema

Monitoring Parameters

• Serum calcium (if risk factors present)
• Assessment of psoriatic involvement (% BSA)
• Renal function (if concerns exist)

• Clinical response (PASI score improvement)
• Local skin reactions
• Serum calcium every 3-6 months if using high doses or with risk factors
• Signs of hypercalcemia (fatigue, nausea, constipation)

• Annual calcium monitoring with chronic use
• Skin examination for signs of atrophy or hypopigmentation

Patient Education

• Apply only to affected areas, not surrounding healthy skin
• Use sparingly; a thin layer is sufficient
• Wash hands thoroughly after application
• Avoid contact with eyes, mouth, and mucous membranes

• Avoid excessive sun exposure; use sunscreen
• Do not occlude treated areas unless directed
• Moisturizers may be used 30 minutes after application

• Report any severe skin irritation or worsening of condition
• Watch for signs of high calcium: nausea, vomiting, constipation, fatigue
• Do not exceed prescribed amount or frequency
• Inform all healthcare providers about calcipotriene use

• Store at room temperature (15-30°C)
• Keep tube tightly closed
• Do not freeze

References

1. FDA Prescribing Information: Calcipotriene Ointment, 2023 2. Lebwohl MG, et al. J Am Acad Dermatol. 2021;84(2):432-440 3. Mason AR, et al. Cochrane Database Syst Rev. 2013;(3):CD010056 4. van de Kerkhof PCM, et al. Br J Dermatol. 2018;179(5):1069-1077 5. American Academy of Dermatology Psoriasis Guidelines, 2019 6. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier; 2021 7. Bolognia JL, et al. Dermatology. 4th ed. Elsevier; 2018 8. UpToDate: Calcipotriene drug information, 2023 9. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023 10. National Psoriasis Foundation Treatment Guidelines, 2022