Dovonex - Product Information
|Condition:||Plaque Psoriasis, Psoriasis|
|Form:||Cream, gel, liniment or balm, lotion, ointment, etc|
|Ingredients:||Calcipotriol, white soft paraffin, propylene glycol, liquid paraffin, polyoxyethylene-(2)-stearyl ether, purified water,disodium phosphate dehydrate, disodium edentate, DL-α-tocopherol, white soft paraffin, cetostearyl alcohol, liquid paraffin, glycerol 85%, macrogol cetostearyl ether, disodium phosphate dehydrate, disodium edentate, chloroallylhexaminium (dowicil 200), purified water|
Summary product information
|Dosage Form / Strength
||Clinically Relevant Nonmedicinal
|topical||Ointment and Cream, 50 mcg/g calcipotriol
Scalp solution, 50 mcg/mL calcipotriol
For a complete listing see Dosage
Forms, Composition and Packagingsection.
Indications and clinical use
DOVONEX (calcipotriol) cream and ointment is indicated for:
- the topical treatment of psoriasis
- combination use with a moderate to very potent topical corticosteroid, cyclosporin A or acitretin.
DOVONEX scalp solution is indicated for:
- the topical treatment of scalp psoriasis.
DOVONEX cream, ointment and scalp solution are not generally recommended for severe extensive psoriasis.
DOVONEX is not recommended for use on the face.
- Patients who are hypersensitive to DOVONEX (calcipotriol) cream, ointment or scalp solution, to any ingredient in the formulations or components of the containers. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.
- NOT FOR OPHTHALMIC USE.
- When DOVONEX is used in combination with other antipsoriatic therapies, all available information on “CONTRAINDICATIONS” for the other antipsoriatic therapy/therapies apply and should be considered.
Warnings and precautions
Calcipotriol when used in combination with ultra-violet radiation (UVR) may enhance the known skin carcinogenic effect of UVR. This potential risk is based on the preclinical finding in mice of a reduced time to tumor formation from long term exposure to UVR and topically applied calcipotriol (see TOXICOLOGY, Carcinogenicity)
When DOVONEX (calcipotriol) is used in combination with other antipsoriatic therapies, all available information on “WARNINGS AND PRECAUTIONS” for the other antipsoriatic therapy/therapies apply and should be considered.
DOVONEX cream, ointment and scalp solution are not generally recommended for severe extensive psoriasis. If calcipotriol is used for severe extensive psoriasis, it is important to monitor the serum calcium levels at regular intervals due to the risk of hypercalcemia secondary to excessive absorption of calcipotriol when there is extensive skin involvement. If the serum calcium level becomes elevated, calcipotriol therapy should be discontinued and the serum calcium level monitored in these patients until it returns to normal.
DOVONEX is not recommended for use on the face since this may give rise to itching and erythema of the facial skin. Patients should be instructed to wash their hands after using calcipotriol to avoid inadvertent transfer to the face from other body parts. Should facial dermatitis develop in spite of these precautions, calcipotriol therapy should be discontinued.
DOVONEX should be used cautiously in skin folds, where the natural occlusion may give rise to an increase of the irritant effect of calcipotriol.
Safety for use during pregnancy has not yet been established, although studies in experimental animals have not shown teratogenic effects. Calcipotriol should be used in women during pregnancy only if the anticipated benefit clearly outweighs the potential risk.
It is not known whether calcipotriol could be excreted in breast milk. Calcipotriol should be used in women during breast feeding only if the anticipated benefit clearly outweighs the potential risk.
Infants (< 2yrs of age)
There is inadequate experience with the use of calcipotriol in infants under 2 years of age to recommend use in this age group. Use beneath diapers has not been investigated and should be avoided as diapers may be occlusive.
Pediatrics (2-14 years of age)
Administration to children should be supervised by a responsible individual to ensure proper administration and dosage. There is no experience in children with the use of DOVONEX in combination with other antipsoriatic therapies.
Monitoring and Laboratory Tests
Treatment with DOVONEX in the recommended amounts (See DOSAGE AND ADMINISTRATION) does not generally result in changes in laboratory values. However, it is recommended that baseline serum calcium levels be obtained in all patients before starting treatment with calcipotriol, with subsequent monitoring of these serum calcium levels at suitable intervals. The monitoring of serum calcium levels is particularly important if the total dose of calcipotriol exceeds the recommended amount or if calcipotriol is used for severe psoriasis with extensive skin involvement. If serum calcium becomes elevated, calcipotriol treatment should be discontinued and the levels of serum calcium should be measured once weekly until the serum calcium levels return to normal values. Patients with marginally elevated serum calcium may be treated with calcipotriol, provided that serum calcium is monitored at suitable intervals.
In clinical trials reported to-date, the most common adverse reactions have been related to lesional and perilesional irritation. Some patients develop face and scalp irritation which is likely related to the inadvertent transfer of DOVONEX (calcipotriol) cream or ointment from other body parts. Facial irritation may also occur with the use of DOVONEX scalp solution from inadvertent transfer of the scalp solution to the face. One unconfirmed case of Koebner phenomenon and three unconfirmed cases of hypersensitivity reaction to calcipotriol have been reported. Occasionally hypercalcemia has been reported usually related to excessive (greater than the recommended weekly amount - See DOSAGE AND ADMINISTRATION) use of topical calcipotriol or when excessive absorption of calcipotriol has occurred when used for severe psoriasis with extensive skin involvement (See WARNINGS AND PRECAUTIONS).
Clinical studies have shown that combination of DOVONEX once daily plus a moderately potent to very potent topical corticosteroid once daily reduces skin irritation due to calcipotriol. Combination of DOVONEX plus cyclosporin A (2 mg/kg/day) or DOVONEX plus acitretin (20- 70 mg/day) did not affect the incidence of short term adverse effects compared to cyclosporin A or acitretin plus placebo ointment. The combination of Dovonex plus PUVA or UVB phototherapy did not affect the incidence of short term adverse effects compared to PUVA or UVB plus placebo ointment/cream.
With the exception of topical corticosteroids, (See DOSAGE AND ADMINISTRATION), there is no experience of concomitant therapy with other topical antipsoriatic drugs applied to the same skin area.
Dosage and administration
- DOVONEX (calcipotriol) is FOR TOPICAL USE ONLY and not for ophthalmic use.
- There is no clinical trial experience with use of DOVONEX scalp solution in children.
- There is no experience in children with the use of DOVONEX in combination with other antipsoriatic therapies.
Recommended Dose and Dosage Adjustment
The maximum recommended weekly dose of DOVONEX cream and/or ointment is:
|Age (years)||Dovonex Cream or Ointment, g/week||Total Calcipotriol mg/week|
|6 – 10||50||2.5|
|11 – 14||75||3.75|
|Adults (over 14)||100||5|
The maximum weekly dose of DOVONEX cream and/or ointment for children is based on the adult dose of 100 g/week adjusted for body surface area (maximum 50 g/week/m2). The dosage regimen is based on the following expected body surface area: age 2-5 years, 0.5 m2 (25% of adult); age 6-10 years, 1.0 m2 (50% of adult); age 11-14 years, 1.5 m2 (75% of adult).
The maximum recommended adult weekly dose of DOVONEX scalp solution is 60 mL (3 mg calcipotriol).There is no clinical trial experience with use of DOVONEX scalp solution in children.
When the cream, ointment, or scalp solution are used together, the total dose of calcipotriol should not exceed the recommended weekly amount for each age group (i.e. 2-5 years, 1.25 mg; 6-10 years, 2.5 mg; 11-14 years, 3.75 mg; Adults, 5 mg in any week).
If an application of DOVONEX is missed, it should be used as soon as the patient remembers and further dosing resumed as usual.
DOVONEX 50 mcg/g ointment or cream is available for use on the body and; a 50 mcg/mL scalp solution is available for hairy areas.
DOVONEX Used as Monotherapy:
DOVONEX should be applied topically to the affected areas twice daily (i.e. in the morning and in the evening). Application can be reduced to once daily (i.e. in the morning or in the evening) for maintenance treatment when appropriate. After satisfactory improvement has occurred, the drug can be discontinued. If recurrence takes place after discontinuation, the treatment may be reinstituted.
DOVNEX Used as Combination Therapy:
DOVONEX can be used in combination with a moderately potent to very potent topical corticosteroid (See ACTION AND CLINICAL PHARMACOLOGY). DOVONEX and the steroid should be applied once daily at alternate times (i.e. morning versus evening application).
DOVONEX can be used twice daily in combination with low dose cyclosporin A (i.e. 2 mg/kg/ day) or in combination with acitretin (20-70 mg/day) (See ACTIONS AND CLINICAL PHARMACOLOGY).
The use of DOVONEX in combination with other treatments (i.e. topical steroids, cyclosporin A or acitretin) improves efficacy allowing for dosage reduction of the other treatments. There is no experience in children with the use of DOVONEX in combination with other antipsoriatic therapies.
Hypercalcemia does not occur at the usual dose of DOVONEX (calcipotriol) (See DOSAGE AND ADMINISTRATION). Excessive use (i.e. more than the recommended weekly amount) may cause elevated serum calcium, which rapidly subsides when treatment is discontinued. In such cases, the monitoring of serum calcium levels once weekly until the serum calcium returns to normal levels is recommended.
Action and clinical pharmacology
Mechanism of Action
Calcipotriol is a non-steroidal antipsoriatic agent, derived from naturally occurring vitamin D. Calcipotriol exhibits a vitamin D-like effect by competing for the 1,25(OH)2D3 receptor. Calcipotriol is as potent as 1,25(OH)2D3, the naturally occurring active form of vitamin D, in regulating cell proliferation and cell differentiation, but much less active than 1,25(OH)2D3 in its effect on calcium metabolism. Calcipotriol induces differentiation and suppresses proliferation (without any evidence of a cytotoxic effect) of keratinocytes, thus reversing the abnormal keratinocyte changes in psoriasis. The therapeutic goal envisaged with calcipotriol is thus a normalization of epidermal growth.
Clinical trials have shown DOVONEX cream and ointment (calcipotriol 50 mcg/g) and DOVONEX scalp solution (calcipotriol 50 mcg/mL) to be efficacious and well-tolerated in the topical treatment of psoriasis vulgaris (plaque psoriasis). Clinical improvement usually occurred rapidly and was evident within 2 weeks of treatment. The symptoms of thickness, erythema and scaling, as well as extent of psoriasis, were all markedly improved. The efficacy and safety of DOVONEX ointment and cream are similar with best results obtained at the end of up to 6 to 8 weeks of treatment. Long-term control of psoriasis lasting up to 12 months has been demonstrated in clinical trials with DOVONEX ointment.
Clinical trials have demonstrated the efficacy and safety of once daily DOVONEX administration in combination with once daily administration of a moderately potent to very potent topical corticosteroid. Twice daily application of DOVONEX is safe and effective when combined with systemic drug therapy (cyclosporin A or acitretin). In clinical studies, DOVONEX ointment was combined with either cyclosporin A (2 mg/kg/day) for up to 6 weeks or with acitretin (20-70 mg/day) for up to 12 weeks. Improved efficacy achieved through combination therapy allowed once daily steroid administration or reductions in the required dose of cyclosporin A or acitretin, thereby reducing the potential for dose related adverse effects associated with these agents. Combination of DOVONEX plus a moderately potent to very potent corticosteroid was also shown to reduce skin irritation due to calcipotriol. Combination of DOVONEX with systemic drug therapy did not affect the incidence of short term adverse events compared to systemic drug therapy alone.
Three pivotal trials to evaluate the safety and efficacy of DOVONEX scalp solution were conducted in patients with scalp psoriasis. There was a statistically significant improvement in the scalp psoriasis with a positive effect on total sign score, redness, thickness, scaliness and extent of scalp psoriasis.
A pharmacokinetic study of DOVONEX ointment has demonstrated that the apparent systemic absorption of the applied dose of calcipotriol over 12 hours is approximately 5.5% of the dose in normal subjects and in psoriatic patients.
Special Populations and Conditions
The safety, efficacy and tolerability of DOVONEX ointment in children (ages 2 to 14 years) has been demonstrated by an 8 week open-label trial as well as an 8 week double-blind vehicle controlled trial. DOVONEX was significantly more effective than vehicle in reducing the symptoms of redness, thickness and scaliness, and in the overall assessment of efficacy. No significant effects on haematology, serum and urine biochemistry parameters (including calcium levels) and parameters of bone formation or resorption were observed after 8 weeks of treatment (maximum dose 50 g/week/m2 body surface area).
FOR DETAILS OF EFFICACY AND SAFETY DATA OBTAINED FROM VARIOUS CLINICAL TRIALS, SEE PART II – CLINICAL TRIALS.
Storage and stability
Cream: Store at room temperature (15-25oC). Use within 6 months of first opening the tube.
Ointment: Do not store above 25oC. Use within 6 months of first opening the tube.
May be refrigerated. For easy application use at room temperature (this is to prevent pulling of delicate skin).
Scalp Solution: Store below 25oC. Use within 3 months of first opening the bottle.
Dosage forms, composition and packaging
DOVONEX (calcipotriol) is available as an ointment (faintly translucent white to yellowish ointment), cream (white, soft cream), and scalp solution (colourless, slightly viscous solution).
|50 mcg calcipotriol per gram
white soft paraffin
disodium phosphate dihydrate
|50 mcg calcipotriol per gram
white soft paraffin
macrogol cetostearyl ether
disodium phosphate dihydrate
|50 mcg calcipotriol per mL
Cream and ointment: 15g, 60g and 120g lacquered aluminium tubes (equipped with an aluminium membrane).
Scalp solution: 30 mL, 60 mL, and 120 mL polyethylene bottles.