Dovobet® (Calcipotriol and Betamethasone Dipropionate) Overview

Introduction

• Dovobet (50 micrograms/gram calcipotriol and 0.5 milligrams/gram betamethasone dipropionate) is a topical ointment approved for use in Canada to treat plaque psoriasis.
• Dovobet has become the topical therapy of choice for many patients with plaque type psoriasis not involving the face or skin folds

There are limitations for regulators, pharmaceutical companies and pharmaceutical sales representatives to present clinical evidence following development of product monograph and drug approval. The product monograph is the starting point for this A-Detail™. It also contains evidence-based decision making processes, current standards of practice and clinical experience to provide a practical approach to the treatment of this condition.

Disclaimer: This A-Detail™ is meant to be a practical guide and does not necessarily reflect all risks, side-effects or situations associated with this product.

Clinical Experience

• More than six international studies involving over 6,000 patients have shown reductions in the PASI (Psoriasis Area and Severity Index) of approximately 40% after one week of treatment and 70% after four weeks.
• Dovonex (50 micrograms/gram calcipotriol) is often prescribed after four weeks of Dovobet therapy for ongoing maintenance. In practice ongoing use of Dovobet such as on weekends only is common.
• Dovobet is well tolerated. Side effects are minimal: some 5% to 10% of patients report itching or other lesional or perilesional adverse reactions.

Indications

Chronic Plaque Psoriasis

• Used to treat chronic plaque psoriasis that covers less than 30% of the body surface (see following slides for clarification).
• Dovobet is not often used to treat the scalp because the sticky base does not allow for easy application or removal.
• Caution should be used if treating the face or genital area because of the risks of side effects from using long term potent topical corticosteroids.

Patient Profile

• Patients with chronic plaque psoriasis that covers less than 30% of the body surface.
• In some cases, a patient could use it on a greater BSA if he/she wanted to as long as the use/week is 100 g per week or less. This area could be as high as 28 palm sized lesions at approximately .5 g/100 cm2 application rate.

Dosing

• Dovobet should be applied to the affected area once daily for four weeks. Several studies have shown that there are no statistically significant differences between applying the ointment once daily or twice daily.
• No more than 100 g should be used per week.
  Patients should wash their hands carefully after applying Dovobet.
• After the initial four-week treatment, Dovonex or other topicals can may be used as needed for ongoing maintenance.

Efficacy

• Six international studies involving more than 6,000 patients using Dovobet to treat psoriasis have shown PASI reductions of approximately 40% after one week of treatment and 70% after four weeks.
• Additional studies have shown that Dovobet has superior efficacy and a faster onset of action as compared to either active component (calcipotriol or betamethasone dipropionate) on its own in the same base.

Pharmacokinetics

• Patients should apply Dovobet once daily for a four-week period.
• Dovobet is a stable combination of calcipotriol and a potent corticosteroid. Calcipotriol is a proven, safe and effective treatment for psoriasis when used alone; calcipotriol affects keratinocyte differentiation. However, it has a slow onset of action. Topical corticosteroids, such as betamethasone dipropionate, are used to treat psoriasis because they inhibit the inflammatory process. Used together, the two compounds show a high success rate with fewer side effects than if used on their own.
• Dovobet has the potency and safety profile of a class III steroid.

Compliance

Compliance is aided by the convenience of the once daily dosing of Dovobet. Compliance is also less of a problem than with most products due to the rapid onset of action. Significant improvement is usually seen within the first week. The ointment base is cosmetically difficult for some patients. It is therefore normally applied at bedtime.

Side Effects, Safety and Risks

Side Effects

• Because Dovobet is a combination drug, the frequency of side effects reported is less than would be expected if using each compound on its own: for example, the anti-inflammatory action of the corticosteroid (betamethasone dipropionate) minimizes the irritation often reported when using calcipotriol alone.
• Approximately 5% to 10% of patients report itching.
• In a study of over 1000 patients, 9.9% reported lesional or perilesional adverse reactions.
• No changes have been reported in serum calcium.

Risks

• The recommended treatment period is 4 weeks. In this period the majority of patients will benefit satisfactorily. However some patients will require longer treatment than 4 weeks which should be based on physicians‘ assessment of the benefit/risks of continuing the treatment regimen, as prolonged use of steroids can interfere with collagen production and vascular stability producing skin atrophy and purpura.
• Dovobet should not be used concurrently with other corticosteroid creams or ointments.

Monitoring

• Monitor for clinical improvement in the skin as well as for side effects such as atrophy, purpura, perioral dermatitis, rosacea and other side effects of topical steroids.
• Monitoring of serum calcium is not necessary when the recommended quantities are used.

Cost of Treatment

• It is probably the single most effective topical therapy available for psoriasis, so patients are generally prepared to pay for this.
• It is somewhat more expensive than the equivalent potent topical steroid, but the rapid and significant improvement in quality of life in many patients leads many patients and physicians to rate Dovobet as being of very high value.
• The wholesale price of the 120 gram tube is $192.00. This would be enough ointment to treat a patient with 8 palm sized lesions for 4 weeks or to treat a patient with 4 palm sized lesions for 2 rounds of 4 week treatments.
• Dovobet should be used within 12 months of opening the tube to ensure stability.
• Dovobet is covered by most private drug plans in Canada.