1. Name Of The Medicinal Product
Dovonex® Cream
2. Qualitative And Quantitative Composition
Calcipotriol 50 micrograms per g (as the hydrate)
For full list of excipients, see section 6.1
3. Pharmaceutical Form
Cream
Soft white cream
4. Clinical Particulars
4.1 Therapeutic Indications
Dovonex® Cream is indicated for the topical treatment of plaque psoriasis (psoriasis vulgaris) amenable to topical therapy.
4.2 Posology And Method Of Administration
Adults: | Dovonex® Cream should be applied to the affected area once or twice daily. For maximum benefit use the cream twice daily. Maximum weekly dose should not exceed 100g. |
Children over 12 years: | Dovonex® Cream should be applied to the affected area twice daily. Maximum weekly dose should not exceed 75g. |
Children aged 6 to 12 years: | Dovonex® Cream should be applied to the affected area twice daily. Maximum weekly dose should not exceed 50g. |
Children under 6 years: | There is limited experience of the use of Dovonex® in this age group. A maximum safe dose has not been established. |
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 15g 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® Cream is contra-indicated in patients with known disorders of calcium metabolism and patients with severe liver and kidney disease. As with other topical preparations, Dovonex® Cream 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® Cream should not be used on the face. Patients should be advised to wash their hands after applying the cream 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, which rapidly reversed on cessation of treatment, has been reported in patients with generalized pustular or erythrodermic exfoliative psoriasis. However, serum calcium is quickly normalised when treatment is discontinued.
During treatment with Dovonex® Cream 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
Very common | >1/10 |
Common | >1/100 and <1/10 |
Uncommon | >1/1,000 and <1/100 |
Rare | >1/10,000 and <1/1,000 |
Very rare | <1/10,000 |
Approximately 25% of the patients treated with Dovonex® Cream could experience an adverse reaction. These reactions are usually mild.
Immune system disorders | |
Very rare: | allergic reactions (including angioedema). |
Metabolism and nutrition disorders | |
Very rare: | hypercalcaemia, hypercalciuria, especially if the total recommended dose is exceeded (see section 4.2). |
Skin and subcutaneous tissue disorders | |
Very common: | skin irritation |
Common: | rash*, burning sensation, stinging sensation, dry skin, pruritus, erythema, contact dermatitis including facial and perioral. |
Uncommon: | psoriasis aggravated, eczema |
Unknown frequency: | transient changes in skin pigmentation, transient photosensitivity, urticaria, angioedema, periorbital or face oedema. |
*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 rapidly subsides when the 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
Calcipotriol is only slightly absorbed from the skin.
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 90µg/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
Macrogol cetostearyl ether, cetostearyl alcohol, chloroallylhexaminium chloride, disodium edetate, disodium phosphate dihydrate, glycerol 85%, liquid paraffin, sodium hydroxide, purified water, white soft paraffin.
6.2 Incompatibilities
Should not be mixed with other medicinal products.
6.3 Shelf Life
2 years.
6.4 Special Precautions For Storage
Store below 25°C
6.5 Nature And Contents Of Container
Aluminium tubes of 30g (OP), 60g (OP), 100g (OP) and 120g (OP).
Physician Sample Packs: Aluminium tubes of 15g
Polyethylene – aluminium laminate tubes with screw cap of 240g (OP).
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
8. Marketing Authorisation Number(S)
PL 0043/0188
9. Date Of First Authorisation/Renewal Of The Authorisation
10 August 1993
10. Date Of Revision Of The Text
October 2010
No comments:
Post a Comment