Daivobet® is the first and only dual-action therapy offering the benefit of two complementary mechanisms of action, a topical steroid in the form of betamethasone dipropionate and a vitamin D3 analogue, calcipotriol.
This newly available therapeutic option is the result of scientific advancements in formation chemistry for topical therapies that created a dose-stable, penetration-enhanced mixture.
Relative to either individual ingredient, Daivobet® is clinically proven to achieve:
Faster clearance of plaques
Greater total PASI reduction and physician global assessment of improvement
Higher rates of patient compliance and satisfaction
Product names
The trademarks registered by LEO Pharma for the combination product are: Daivobet® ointment, Dovobet® ointment, Psorcutan Beta® ointment, Delcibel® ointment and Taclonex® ointment. The product name Daivobet® is used in Denmark, the first country of launch. In Canada and the UK, the product name is Dovobet®.
Formulation
One gram of Daivobet® ointment contains calcipotriol 50mcg (as hydrate) and betamethasone 0.5mg (as dipropionate).
Packaging
Daivobet® is available in pack sizes of 3g (sample pack), 15g, 30g, 60g, and 120g. Not all pack sizes may be marketed.
Daivobet® is a two-compound product containing calcipotriol 50 mcg (as hydrate) and betamethasone 0.5 mg (as dipropionate). Vitamin D3 analogues and topical steroids work on psoriasis vulgaris in different ways. Treatment with a combined formulation of these two agents controls psoriasis by optimizing the antiproliferative and anti-inflammatory mechanisms inherent to both products.
Calcipotriol (the active agent in Daivonex®) affects keratinocyte differentiation (Reichrath et al. 1997). The binding of calcipotriol to the vitamin D receptor in skin cells initiates a series of cellular events that result in inhibition of cell proliferation, stimulation of cell differentiation, and regulation of the inflammatory response.
Betamethasone dipropionate is anti-inflammatory (Ortonne et al. 1994). Topical steroids are absorbed through the epidermis where they bind to the glucocorticoid receptor, eliciting an anti-inflammatory response as well as reducing keratinocyte cell division.
Vitamin D3 analogues such as calcipotriol primarily exhibit antiproliferative effects on the skin, while steroids have both antiinflammatory and antiproliferative properties. By using the two compounds together, greater efficacy may be achieved with a rapid response. The potential efficacy of such combinations (with separate application of calcipotriol and topical steroid) has been confirmed in clinical trials (Ortonne et al. 1994; Kragballe et al. 1998; Ruzicka & Lorenz 1998; Lebwohl et al. 1996).
Until the development of Daivobet®, calcipotriol and topical steroids could not be applied simultaneously. Calcipotriol and betamethasone dipropionate have optimal stability at different pH levels.
Calcipotriol requires an alkaline environment for stability, whereas betamethasone dipropionate requires an acidic environment. The calcipotriol molecule is relatively unstable and is inactivated by low pH.
As a consequence, simultaneous application of the two marketed products may result in degradation of one or both active substances. Likewise, mixing of the two marketed products is not recommended. Mixing topical corticosteroids with other topical agents may introduce uncertainty as to the shelf life of the preparation. Evidence suggests that calcipotriol can also be unstable when mixed with other topical preparations (Patel et al. 1998). One or both ingredients may be inactivated after a few hours or days.
Daivobet® has been developed in order to combine calcipotriol and betamethasone dipropionate, two otherwise incompatible substances, into one application. Simultaneous application of both agents is not only more convenient for the patient, it also maximises the opportunities for an additive or even synergistic effect.
In Daivobet®, calcipotriol is dissolved in a water-free vehicle, in which micronised betamethasone dipropionate is suspended. A penetration enhancer, polyoxypropylene-15-stearyl ether (Arlamol® E), was added at a concentration of 1% to increase penetration of the two components from the vehicle into the skin.
The resulting product, Daivobet®, is stable for up to 2 years with regards to both calcipotriol and betamethasone dipropionate, and is formulated for optimal penetration of both compounds from the vehicle.
Directions:
Daivobet® should be applied to the affected area once daily. The recommended treatment period is 4 weeks. After this period repeated treatment with Daivobet® can be initiated under medical supervision.
