DAIVONEX OINTMENT

Indications

• Plaque psoriasis
• Mild to moderate plaque psoriasis
• Scalp psoriasis

Dosage

Children: For children aged 6–11 years, apply twice daily, with a maximum total calcipotriol of 2.5 mg in any one week. For children aged 12–17 years, apply twice daily, not exceeding 3.75 mg in any one week.

Adults: Apply calcipotriol ointment or scalp solution to the affected areas twice daily. Maximum total calcipotriol dosage should not exceed 5 mg per week.

Mechanism of action

Calcipotriol binds to vitamin D receptors in skin cells, leading to the regulation of gene expression involved in cell proliferation and differentiation. This action promotes the normal maturation of keratinocytes and reduces hyperproliferation, which is a hallmark of psoriatic lesions. Additionally, it exhibits anti-inflammatory properties, further aiding in the management of psoriasis.

Pharmacodynamics

Calcipotriol has a dose-dependent effect on keratinocyte proliferation and differentiation. It decreases the production of pro-inflammatory cytokines and chemokines, which are elevated in psoriasis. The therapeutic effects are typically observed within a few weeks of treatment, with optimal results often seen after sustained use. Side effects may include local skin irritation and an increased risk of hypercalcemia, especially if used excessively.

Pharmacokinetics

When applied topically, calcipotriol is minimally absorbed through intact skin. Systemic absorption can occur, particularly when applied to large areas or under occlusion. The half-life of calcipotriol is approximately 1.5 hours in systemic circulation, but its effects persist due to its action on skin cells. The drug is metabolized primarily in the liver, with metabolites excreted through urine and feces.

Contra-indications

• Calcium metabolism disorders
• Erythrodermic exfoliative psoriasis
• Generalised pustular psoriasis
• Do not apply under occlusion

Adverse effects

• Skin reactions
• Hypercalcaemia
• Hypercalciuria
• Photosensitivity reactions
• Increased risk of infection

Interactions

• Acitretin

Precautions

• Avoid excessive exposure to sunlight
• Avoid broken or inflamed skin
• Caution in patients with renal impairment
• Caution in patients with hepatic impairment

Pregnancy

Manufacturers advise avoidance unless essential.

Breast-feeding

No information available.

Storage

Store in a cool, dry place away from light.

Formulations

• Calcipotriol 50 micrograms/g ointment
• Calcipotriol scalp solution

Mechanism of action

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 while being less than 1% the activity in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis and are believed to undergo modulation of gene expression with binding of calcipotriol to the VDR. This modulation is thought to affect gene products related to cell differentiation and proliferation.

Pharmacodynamics

Calcipotriene is a synthetic analog of vitamin D. In humans, the natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol) in the skin.