Dovonex
Summary of product characteristics
1. Name of the medicinal product
Dovonex® Ointment
2. Qualitative and quantitative composition
Each gram of ointment contains 50 micrograms of calcipotriol.
Excipient(s) with known effect:
Propylene glycol 100 mg/g
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Ointment
Off white to yellowish white translucent ointment.
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
| Adults:
| Dovonex®* Ointment should be applied to the affected area once or twice daily. For maximum benefit use the ointment twice daily. Maximum weekly dose should not exceed 100 g.
|
| Children over 12 years:
| Dovonex®* Ointment should be applied to the affected area twice daily. Maximum weekly dose should not exceed 75 g.
|
| Children aged 6 to 12 years:
| Dovonex®* Ointment should be applied to the affected area twice daily. Maximum weekly dose should not exceed 50 g.
|
| Children under 6 years:
| There is limited experience of the use of Dovonex®* Ointment 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 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
Hypersensitivity to the active substance or any of the excipients listed in section 6.1
Due to the content of calcipotriol, Dovonex® is contraindicated in patients with known disorders of calcium metabolism (see section 4.4).
4.4. Special warnings and precautions for use
Effects on calcium metabolism
Due to the content of calcipotriol, 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. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the dosage recommendations are followed. The maximum weekly dose in adults is 100 g of cream or ointment (equivalent to 5 mg of calcipotriol) or 60 ml of scalp solution (equivalent to 3 mg of calcipotriol). When cream, ointment or cutaneous solution are applied together, the total dose of calcipotriol should not exceed 5 mg per week.
Local adverse reactions
Dovonex® should not be applied to the face, as it may cause skin irritation
The patient must be instructed in correct use of the product to avoid accidental transfer to the face and eyes. Hands must be washed after each application to avoid accidental transfer to these areas.
UV exposure
During Dovonex®* Ointment treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Dovonex®* 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).
Unevaluated use
Due to lack of data, Dovonex®* should be avoided in guttate, erythrodermic, exfoliative and pustular psoriasis.
Due to lack of data, Dovonex®* should be avoided in patients with severe liver and kidney disease.
Adverse reactions to excipients
Dovonex®* ointment contains propylene glycol as an excipient which may cause skin irritation.
Fire hazard
Instruct patients not to smoke or go near naked flames – risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.
4.5. Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with Dovonex®*.
4.6. Fertility, pregnancy and lactation
Pregnancy
The safety of the use of topical calcipotriol during human pregnancy has not been established, however studies in animals have shown reproductive toxicity when calcipotriol was administered orally. Calcipotriol should not be used during pregnancy unless clearly necessary.
Breast-feeding
It is unknown whether calcipotriol is excreted in breast milk. Caution should be exercised when prescribing Dovonex®* to women who breast-feed. The patient should be instructed not to use Dovonex®* on the breast when breast-feeding.
Fertility
Studies in rats with oral doses of calcipotriol demonstrated no impairment of male and female fertility.
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
The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies and spontaneous reporting.
The most frequently reported adverse reactions during treatment are pruritus, skin irritation and erythema.
Systemic reactions (hypercalcaemia and hypercalciuria) have been reported. The risk of developing such reactions increases if the recommended total dose is exceeded (see section 4.4).
Adverse reactions are listed by MedDRA SOC and the individual adverse reactions are listed starting with the most frequently reported. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
| Very common
| ≥1/10
|
| Common
| ≥1/100 to <1/10
|
| Uncommon
| ≥1/1,000 to <1/100
|
| Rare
| ≥1/10,000 to <1/1,000
|
| Very rare
| <1/10,000
|
Approximately 25% of the patients treated with Dovonex®* Ointment could experience an adverse reaction. These reactions are usually mild.
|
Infections and infestations
| |
| Uncommon (≥1/1,000 to <1/100)
| Folliculitis
|
|
Immune system disorders
| |
| Rare (≥1/10,000 to <1/1,000)
| Hypersensitivity
|
|
Metabolism and nutrition disorders
| |
| Rare (≥1/10,000 to <1/1,000)
| Hypercalcaemia
|
|
Skin and subcutaneous tissue disorders
| |
| Common (≥1/100 to < 1/10)
| Psoriasis aggravated Dermatitis Erythema Skin exfoliation Skin burning sensation Skin irritation Pruritus
|
| Uncommon (≥1/1,000 to <1/100)
| Rash* Dry skin
|
| Rare (≥1/10,000 to <1/1,000)
| Photosensitivity reaction Skin oedema Urticaria Seborrhoeic dermatitis
|
|
Renal and urinary disorders
| |
| Rare (≥1/10,000 to <1/1,000)
| Hypercalciuria
|
|
General disorders and administration site conditions
| |
| Common (≥1/100 to <1/10)
| Application site pain
|
| Uncommon (≥1/1,000 to <1/100)
| Application site pigmentation changes
|
* Various types of rash reactions such as rash erythematous, rash maculo-papular, rash morbilliform, rash papular and rash pustular have been reported.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
Use above the recommended dose may cause elevated serum calcium which subsides when treatment is discontinued. The symptoms of hypercalcemia include polyuria, constipation, muscle weakness, confusion and coma.
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 0.3-1.7 g of a 50 micrograms/g tritium labelled calcipotriol ointment suggested that less than 1% of the dose was absorbed.
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 and an oral carcinogenicity study in rats 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.
6.1. List of excipients
Disodium edetate
Disodium phosphate dihydrate
All-rac-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
Maidenhead
Berkshire
SL6 3UD
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
13 July 2023
* Dovonex® for proprietary product. Calcipotriol for non-proprietary product.
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
| Adults:
| Dovonex®* Ointment should be applied to the affected area once or twice daily. For maximum benefit use the ointment twice daily. Maximum weekly dose should not exceed 100 g.
|
| Children over 12 years:
| Dovonex®* Ointment should be applied to the affected area twice daily. Maximum weekly dose should not exceed 75 g.
|
| Children aged 6 to 12 years:
| Dovonex®* Ointment should be applied to the affected area twice daily. Maximum weekly dose should not exceed 50 g.
|
| Children under 6 years:
| There is limited experience of the use of Dovonex®* Ointment 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 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
Hypersensitivity to the active substance or any of the excipients listed in section 6.1
Due to the content of calcipotriol, Dovonex® is contraindicated in patients with known disorders of calcium metabolism (see section 4.4).
4.4 Special warnings and precautions for use
Effects on calcium metabolism
Due to the content of calcipotriol, 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. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the dosage recommendations are followed. The maximum weekly dose in adults is 100 g of cream or ointment (equivalent to 5 mg of calcipotriol) or 60 ml of scalp solution (equivalent to 3 mg of calcipotriol). When cream, ointment or cutaneous solution are applied together, the total dose of calcipotriol should not exceed 5 mg per week.
Local adverse reactions
Dovonex® should not be applied to the face, as it may cause skin irritation
The patient must be instructed in correct use of the product to avoid accidental transfer to the face and eyes. Hands must be washed after each application to avoid accidental transfer to these areas.
UV exposure
During Dovonex®* Ointment treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Dovonex®* 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).
Unevaluated use
Due to lack of data, Dovonex®* should be avoided in guttate, erythrodermic, exfoliative and pustular psoriasis.
Due to lack of data, Dovonex®* should be avoided in patients with severe liver and kidney disease.
Adverse reactions to excipients
Dovonex®* ointment contains propylene glycol as an excipient which may cause skin irritation.
Fire hazard
Instruct patients not to smoke or go near naked flames – risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with Dovonex®*.
4.6 Fertility, pregnancy and lactation
Pregnancy
The safety of the use of topical calcipotriol during human pregnancy has not been established, however studies in animals have shown reproductive toxicity when calcipotriol was administered orally. Calcipotriol should not be used during pregnancy unless clearly necessary.
Breast-feeding
It is unknown whether calcipotriol is excreted in breast milk. Caution should be exercised when prescribing Dovonex®* to women who breast-feed. The patient should be instructed not to use Dovonex®* on the breast when breast-feeding.
Fertility
Studies in rats with oral doses of calcipotriol demonstrated no impairment of male and female fertility.
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
The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies and spontaneous reporting.
The most frequently reported adverse reactions during treatment are pruritus, skin irritation and erythema.
Systemic reactions (hypercalcaemia and hypercalciuria) have been reported. The risk of developing such reactions increases if the recommended total dose is exceeded (see section 4.4).
Adverse reactions are listed by MedDRA SOC and the individual adverse reactions are listed starting with the most frequently reported. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
| Very common
| ≥1/10
|
| Common
| ≥1/100 to <1/10
|
| Uncommon
| ≥1/1,000 to <1/100
|
| Rare
| ≥1/10,000 to <1/1,000
|
| Very rare
| <1/10,000
|
Approximately 25% of the patients treated with Dovonex®* Ointment could experience an adverse reaction. These reactions are usually mild.
|
Infections and infestations
| |
| Uncommon (≥1/1,000 to <1/100)
| Folliculitis
|
|
Immune system disorders
| |
| Rare (≥1/10,000 to <1/1,000)
| Hypersensitivity
|
|
Metabolism and nutrition disorders
| |
| Rare (≥1/10,000 to <1/1,000)
| Hypercalcaemia
|
|
Skin and subcutaneous tissue disorders
| |
| Common (≥1/100 to < 1/10)
| Psoriasis aggravated Dermatitis Erythema Skin exfoliation Skin burning sensation Skin irritation Pruritus
|
| Uncommon (≥1/1,000 to <1/100)
| Rash* Dry skin
|
| Rare (≥1/10,000 to <1/1,000)
| Photosensitivity reaction Skin oedema Urticaria Seborrhoeic dermatitis
|
|
Renal and urinary disorders
| |
| Rare (≥1/10,000 to <1/1,000)
| Hypercalciuria
|
|
General disorders and administration site conditions
| |
| Common (≥1/100 to <1/10)
| Application site pain
|
| Uncommon (≥1/1,000 to <1/100)
| Application site pigmentation changes
|
* Various types of rash reactions such as rash erythematous, rash maculo-papular, rash morbilliform, rash papular and rash pustular have been reported.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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