1. Name Of The Medicinal Product
Dovonex ® Ointment
2. Qualitative And Quantitative Composition
Calcipotriol 50 micrograms per g
For full list of excipients, see section 6.1
3. Pharmaceutical Form
Ointment
Off white to yellowish white translucent ointment.
4. Clinical Particulars
4.1 Therapeutic Indications
Dovonex ® Ointment is indicated for the topical treatment of plaque psoriasis (psoriasis vulgaris) amenable to topical therapy.
4.2 Posology And Method Of Administration
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These dose recommendations are based on extensive experience in adults. In respect of children, clinical experience in children has shown Dovonex ® to be safe and effective over eight weeks at a mean dose of 15 g per week but with wide variability in dose among patients. Individual dose requirement depends on the extent of psoriasis but should not exceed the above recommendations. There is no experience of use of Dovonex ® in combination with other therapies in children.
4.3 Contraindications
Dovonex ® Ointment is contraindicated in patients with known disorders of calcium metabolism and patients with severe liver and kidney disease. As with other topical preparations, Dovonex ® Ointment is contra-indicated in patients with hypersensitivity to the active substance or any of the excipients.
4.4 Special Warnings And Precautions For Use
Dovonex ® Ointment should not be used on the face. Patients should be advised to wash their hands after applying the ointment and to avoid inadvertent transfer to other body areas, especially the face.
The risk of hypercalcaemia is minimal when the dosage recommendations are followed. Hypercalcaemia may occur if the maximum weekly dose is exceeded. Care should be exercised in patients with other types of psoriasis, since hypercalcaemia has been reported in patients with generalised pustular or erythrodermic exfoliative psoriasis. However, serum calcium is quickly normalised when treatment is discontinued.
During treatment with Dovonex ® Ointment physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Topical calcipotriol should be used with UV radiation only if the physician and patient consider that the potential benefits outweigh the potential risks (see section 5.3).
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
There is no experience of concomitant therapy with other antipsoriatic products applied to the same skin area at the same time.
4.6 Pregnancy And Lactation
Pregnancy
The safety of the use of calcipotriol during human pregnancy has not been established, and studies in animals have shown reproductive toxicity when calcipotriol was administered orally. Calcipotriol should not be used during pregnancy unless clearly necessary.
Lactation
It is not known whether calcipotriol is excreted in breast milk. A decision on whether to abstain from breast-feeding or to abstain from therapy with Dovonex ® should be made taking into account the benefit of breast-feeding to the newborn/infant and the benefit of Dovonex ® therapy to the woman.
4.7 Effects On Ability To Drive And Use Machines
Calcipotriol has no or negligible influence on the ability to drive and to use machines.
4.8 Undesirable Effects
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Approximately 25% of the patients treated with Dovonex ® Ointment could experience an adverse reaction. These reactions are usually mild.
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Various types of rash reactions such as scaly, erythematous, maculo-papular, pustular, bullous have been reported.
4.9 Overdose
Use above the recommended dose may cause elevated serum calcium which quickly subsides when treatment is discontinued.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
ATC Code: D05A X02
Pharmacotherapeutic group: Antipsoriatics for topical use
Calcipotriol is a vitamin D derivative. In vitro data suggest that calcipotriol induces differentiation and suppresses proliferation of keratinocytes. This is the proposed basis for its effect in psoriasis.
5.2 Pharmacokinetic Properties
Data from a single study containing 5 evaluable patients with psoriasis treated with 0.3
However, total recovery of the tritium label over a 96 hour period ranged from 6.7 to only 32.6%, figures maximised by uncorrected chemiluminescence. There were no data on 3H tissue distribution or excretion from the lungs.
5.3 Preclinical Safety Data
The effect on calcium metabolism is approximately 100 times less than that of the hormonally active form of vitamin D3.
Calcipotriol has shown maternal and foetal toxicity in rats and rabbits when given by the oral route at doses of 54 µg/kg/day and 12 µg/kg/day, respectively. The foetal abnormalities observed with concomitant maternal toxicity included signs indicative of skeletal immaturity (incomplete ossification of the pubic bones and forelimb phalanges, and enlarged fontanelles) and an increased incidence of supernumerary ribs.
There is insufficient pharmacokinetic data available to quantify the safety margin for the embryofoetal effects.
A dermal carcinogenicity study in mice revealed no special hazard to humans.
In a study where albino hairless mice were repeatedly exposed to both ultraviolet (UV) radiation and dermally administered calcipotriol for 40 weeks at dose levels corresponding to 9, 30 and 90 µg/m2/day (equivalent to 0.25, 0.84, 2.5 times the maximum recommended daily dose for a 60 kg adult, respectively), a reduction in the time required for UV radiation to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UV radiation to induce skin tumours. The clinical relevance of these findings is unknown.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Disodium edetate
Disodium phosphate dihydrate
DL-α-tocopherol
Liquid paraffin
Macrogol (2) stearyl ether
Propylene glycol
Purified water
White soft paraffin
6.2 Incompatibilities
Should not be mixed with other medicinal products.
6.3 Shelf Life
Unopened container: 2 years.
After first opening of container: 6 months.
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
Lacquered aluminium tube with polypropylene screw cap.
Pack sizes: 30 g, 60 g, 100 g and 120 g.
Sample packs of 5 g and 15 g.
Polyethylene - aluminium laminate tube with screw cap.
Pack size: 240 g.
Not all pack sizes may be marketed.
6.6 Special Precautions For Disposal And Other Handling
No special requirements
7. Marketing Authorisation Holder
LEO Laboratories Limited
Longwick Road
Princes Risborough
Bucks
HP27 9RR
UK
8. Marketing Authorisation Number(S)
PL 00043/0177
9. Date Of First Authorisation/Renewal Of The Authorisation
10 January 1991
10. Date Of Revision Of The Text
August 2011
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