Medicines
SmPC of 30/04/2024
DAIVOBET 50 micrograms/0,5 mg/g, gel
Composition
Calcipotriol ....................................................................................................................50 micrograms
As calcipotriol monohydrate
Betamethasone..............................................................................................................................0,5 mg
As betamethasone dipropionate
Per 1 g of gel.
Excipients with known effect: 1 g of gel contains 160 micrograms of butylhydroxytoluene and 20 mg of castor oil.
Liquid paraffin, polyoxypropylene stearyl ether, hydrogenated castor oil, butylhydroxytoluene (E321), all-rac-alpha-tocopherol.
Indications
Topical treatment of scalp psoriasis in adults.
Topical treatment of mild to moderate plaque psoriasis vulgaris outside the scalp in adults.
Dosage and administration
Dosage
Daivobet gel should be applied once daily to the lesions. The recommended duration of treatment is 4 weeks for the scalp and 8 weeks outside the scalp. If it is necessary to continue or resume treatment after this period, treatment should be continued following medical advice and under regular medical supervision.
When using products containing calcipotriol, the maximum daily dose must not exceed 15 g. The body surface area treated with products containing calcipotriol must not exceed 30 % (see section Warnings and precautions).
If used on the scalp
All affected areas of the scalp may be treated with Daivobet gel. Usually, an amount between 1 g and 4 g per day is sufficient to treat the scalp (4 g corresponds to one teaspoon).
Special populations
Renal and hepatic impairment
The safety and efficacy of Daivobet gel in patients with severe renal impairment or severe hepatic disorders have not been evaluated.
Paediatric population
The safety and efficacy of Daivobet gel in children under 18 years of age have not been established. The data currently available in children aged 12 to 17 years are described in sections Adverse effects and Pharmacodynamics but no dosage recommendation can be made.
Method of administration
Daivobet gel must not be applied directly to the face or eyes. For optimal effect, it is not recommended to take a shower or bath, or to wash the hair in case of application to the scalp, immediately after applying Daivobet gel. Daivobet gel should remain on the skin during the night or during the day.
Use of the applicator
Before first use of the applicator, the cartridge and the applicator head must be assembled.
After priming, each pump press delivers 0,05 g of gel.
Daivobet gel is applied to the lesions using the applicator. If gel comes into contact with the fingers, wash hands after using Daivobet.
The Daivobet gel applicator is accompanied by a leaflet containing detailed instructions for use.
Use of the bottle
The bottle must be shaken before use and Daivobet gel applied to the lesions.
Wash hands after use.
Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section Composition.
Daivobet is contraindicated in erythrodermic, exfoliative and pustular psoriasis.
Due to the presence of calcipotriol, Daivobet is contraindicated in patients with a history of calcium metabolism disorders (see section Warnings and precautions).
Due to the presence of corticosteroids, Daivobet is contraindicated in the following cases: skin lesions of viral origin (for example herpes or chickenpox), skin infections of fungal or bacterial origin, parasitic infections, skin involvement related to tuberculosis, perioral dermatitis, skin atrophy, striae, fragility of the cutaneous venous network, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds (see section Warnings and precautions).
Warnings and precautions
Effects on the endocrine system
Daivobet gel contains a high-potency corticosteroid (group III) and simultaneous use of other corticosteroids should be avoided. Adverse effects observed with systemic corticosteroid treatment, such as suppression of the hypothalamic-pituitary axis or an effect on glycaemic control in diabetes mellitus, may also occur with topical corticosteroid treatment due to passage into the systemic circulation.
Application under occlusive dressing should be avoided as it increases systemic absorption of corticosteroids. Application over large areas of damaged skin, on mucous membranes or in skin folds should be avoided as it increases systemic absorption of corticosteroids (see section Adverse effects).
In a study of patients with psoriasis extending to both the scalp and the body, using high doses of Daivobet gel in combination (application to the scalp) and high doses of Daivobet ointment (application to the body), 5 patients out of 32 showed a borderline decrease in their cortisol level in response to stimulation by corticotropin (ACTH) after 4 weeks of treatment (see section Pharmacodynamics).
Visual disorders
Visual disturbances may occur with systemic or local corticosteroid therapy. In case of blurred vision or the appearance of any other visual symptom during corticosteroid therapy, an ophthalmological examination is required to look for cataract, glaucoma, or rarer lesions such as central serous chorioretinopathy, as described with systemic or local administration of corticosteroids.
Effects on calcium metabolism
Due to the presence of calcipotriol, hypercalcaemia may occur if the maximum daily dose (15 g) is exceeded. Calcaemia returns to normal upon discontinuation of treatment. The risk of hypercalcaemia is minimal when the recommendations for calcipotriol are followed. Treatment of more than 30 % of the body surface area should be avoided (see section Dosage and administration).
Local adverse effects
Daivobet contains a high-potency corticosteroid (group III) and simultaneous use of other corticosteroids on the same treatment area should be avoided.
The skin of the face and genital area is very sensitive to corticosteroids. The product must not be used in these areas.
The patient should be trained in the correct use of the product in order to avoid accidental application and transfer to the face, mouth and eyes. Wash hands after each application to avoid accidental transfer to these areas.
Concomitant skin infections
When lesions become superinfected, they must be treated with antimicrobial therapy.
However, if the infection worsens, corticosteroid treatment must be discontinued (see section Contraindications).
Discontinuation of treatment
Treatment of psoriasis with topical corticosteroids carries a risk of generalised pustular psoriasis or a rebound effect upon discontinuation of treatment. Medical monitoring should therefore be continued after treatment has been stopped.
Long-term treatment
During long-term treatment, the risk of local and systemic corticosteroid adverse effects is increased. Treatment must be discontinued in the event of adverse effects related to long-term corticosteroid use (see section Adverse effects).
Use not evaluated
There is no data on the use of Daivobet in guttate psoriasis.
Concomitant treatment and UV exposure
Daivobet ointment for psoriasis lesions of the body has been used in combination with Daivobet gel for psoriasis lesions of the scalp, but experience is limited regarding the combination of Daivobet with other topical anti-psoriatic products applied to the same areas, with other systemically administered anti-psoriatic products, or with phototherapy.
During treatment with Daivobet, the physician is advised to counsel patients to limit or avoid excessive exposure to natural or artificial light. Topically applied calcipotriol should be combined with UV only if the physician and the patient consider that the potential benefits outweigh the potential risks (see section Preclinical safety).
Adverse effects related to excipients
Daivobet gel contains butylhydroxytoluene (E321) and castor oil, which may cause local skin reactions (for example: contact dermatitis, eczema), or irritation of the eyes and mucous membranes.
Fertility, pregnancy and breastfeeding
Pregnancy
There are no sufficiently relevant data on the use of Daivobet in pregnant women. Animal studies with glucocorticoids have shown reproductive toxicity (see section Preclinical safety), but a number of epidemiological studies (fewer than 300 pregnancies) have not shown congenital abnormalities in children born to mothers treated with corticosteroids during pregnancy.
The potential risk for humans is not known with certainty. Consequently, Daivobet should be used during pregnancy only when the potential benefit justifies the potential risk.
Breast-feeding
Betamethasone is excreted in breast milk, but the risk of an adverse effect in the infant appears unlikely at therapeutic doses. There are no data on the excretion of calcipotriol in breast milk. Caution is required when prescribing Daivobet to breastfeeding women. The patient should be informed not to apply Daivobet to the breasts during breastfeeding.
Fertility
Studies in rats after oral administration of calcipotriol or betamethasone dipropionate have demonstrated no impairment of fertility in males or females (see section Preclinical safety).
Driving and using machines
Daivobet has no or negligible influence on the ability to drive vehicles and use machines.
Adverse effects
The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies, including post-marketing safety studies, and spontaneous reports.
The most frequently reported adverse reaction during treatment is pruritus.
Adverse reactions are presented by MedDRA System Organ Class (SOC), and individual adverse reactions are presented within each SOC in order of decreasing frequency. Within each frequency group, adverse reactions are presented in order of decreasing seriousness.
|
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) |
|
Not known (frequency cannot be estimated from the available data) |
|
|
Infections and infestations |
|
|
Uncommon ≥ 1/1 000 and < 1/100 |
Skin infection* |
|
Folliculitis |
|
|
Immune system disorders |
|
|
Rare ≥ 1/10 000 and < 1/1 000 |
Hypersensitivity |
|
Eye disorders |
|
|
Uncommon ≥ 1/1 000 and < 1/100 |
Eye irritation |
|
Frequency not known |
Blurred vision***** |
|
Skin and subcutaneous tissue disorders |
|
|
Frequent ≥ 1/100 and < 1/10 |
Pruritus |
|
Uncommon ≥ 1/1 000 and < 1/100 |
Exacerbation of psoriasis |
|
Dermatitis |
|
|
Erythema |
|
|
Skin rash** |
|
|
Acne |
|
|
Skin burning sensation |
|
|
Skin irritation |
|
|
Dry skin |
|
|
Rare ≥ 1/10 000 and < 1/1 000 |
Striae |
|
Skin exfoliation |
|
|
Frequency not known |
Change in hair colour*** |
|
General disorders and administration site conditions |
|
|
Uncommon ≥ 1/1 000 and < 1/100 |
Pain at application site**** |
|
Rare ≥ 1/10 000 and < 1/1 000 |
Rebound effect |
* Reported skin infections include skin infections of bacterial, fungal and viral origin.
** Various types of skin rash have been reported, such as erythematous rash and pustular rash.
*** A transient change in the colour of white or grey hair to a yellowish colour, at the scalp application site, has been reported.
**** Burns at the application site are included in pain at the application site.
***** See section Warnings and precautions.
The following adverse effects, considered to be related to the pharmacological class of calcipotriol and betamethasone, are respectively:
Calcipotriol
Adverse effects include application site reactions, pruritus, skin irritation, burning and tingling sensation, dry skin, erythema, rash, dermatitis, eczema, worsening of psoriasis, photosensitivity and hypersensitivity reactions including very rare cases of angioedema and facial oedema.
Systemic effects following topical application may very rarely occur and cause hypercalcaemia or hypercalciuria (see section Warnings and precautions).
Betamethasone (as dipropionate)
Local reactions may occur after topical use, especially with long-term use, including skin atrophy, telangiectasias, striae, folliculitis, hypertrichosis, perioral dermatitis, contact eczema, depigmentation and colloid milium.
When treating psoriasis with topical corticosteroids, there may be a risk of developing generalised pustular psoriasis.
Systemic effects after topical application of corticosteroids are rare in adults but may be severe. Suppression of the hypothalamic-pituitary axis, cataract, infections, an impact on glycaemic control in diabetes mellitus and an increase in intraocular pressure may occur, particularly after prolonged treatment. Systemic effects occur more frequently with application under occlusion (plastic, skin folds), with application over large areas and with long-term treatment (see section Warnings and precautions).
Paediatric population
During treatment for 8 weeks in 109 adolescents aged 12 to 17 years with scalp psoriasis treated with Daivobet gel, no new adverse events and no new adverse reactions were observed. However, the size of the study does not allow conclusions to be drawn regarding the tolerability profile of Daivobet gel in adolescents compared with adults (see section Pharmacodynamics).
Reporting of suspected adverse reactions
Reporting 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 national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.
Overdose
Use of doses above the recommended dose may lead to an increase in serum calcium, an effect that is reversible on discontinuation of treatment. Symptoms of hypercalcaemia include polyuria, constipation, muscle weakness, confusion and coma.
Excessive and prolonged use of topical corticosteroids may lead to suppression of the hypothalamic-pituitary axis, resulting in secondary adrenal insufficiency that is usually reversible. In such cases, symptomatic treatment is indicated.
In cases of chronic toxicity, corticosteroid treatment should be discontinued gradually.
One case of misuse has been reported in a patient treated for extensive erythrodermic psoriasis with 240 g of Daivobet ointment per week (corresponding to a daily dose of approximately 34 g) for 5 months (maximum recommended dose 15 g per day); during treatment the patient developed Cushing's syndrome and then pustular psoriasis after abrupt discontinuation of treatment.
Pharmacodynamics
Pharmacotherapeutic group: Antipsoriatics. Other antipsoriatics for topical use, calcipotriol, combinations, ATC code: D05AX52.
Calcipotriol is an analogue of vitamin D. Data in vitro suggest that calcipotriol induces differentiation and inhibits proliferation of keratinocytes. This is the proposed mechanism to explain its effects in psoriasis.
Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory, antipruritic, vasoconstrictive and immunosuppressive properties; however, no curative action has been demonstrated. Treatment under occlusion may increase the effect due to greater penetration into the stratum corneum. The incidence of adverse reactions will therefore be increased. In general, the mechanism of action of the anti-inflammatory activity of topical corticosteroids is not fully known.
The adrenal response to ACTH was determined by measuring cortisol levels in patients with both extensive scalp and body psoriasis using up to 106 g per week of Daivobet gel combined with Daivobet ointment. A borderline decrease in cortisol level, 30 minutes after ACTH administration, was observed in 5 of 32 patients (15,6%) after 4 weeks of treatment and in 2 of 11 patients (18,2%) who continued treatment for up to 8 weeks. In all cases, cortisol levels were at a normal level 60 minutes after ACTH administration. No change in calcium metabolism was observed in these patients. Regarding hypothalamic-pituitary suppression, this study shows that at very high doses Daivobet gel and ointment may have a weak effect on the hypothalamic-pituitary axis.
The efficacy of once-daily use of Daivobet gel was evaluated in two randomised, double-blind clinical studies of 8 weeks including a total of more than 2 900 patients with scalp psoriasis of at least mild severity according to the Investigator's Global Assessment of disease severity (IGA). Comparators were betamethasone dipropionate in gel vehicle, calcipotriol in gel vehicle and (in one of the studies) gel vehicle alone, all used once daily.
Results for the primary endpoint (clear or almost clear disease according to IGA at week 8) showed that Daivobet gel was significantly more effective than the comparators. Results on speed of action based on similar data for week 2 also showed that Daivobet gel was significantly more effective than the comparators.
|
% of patients with clear or almost clear disease |
Daivobet gel
|
Betamethasone dipropionate
|
Calcipotriol
|
Gel vehicle
|
|
week 2 |
53,2 % |
42,8 %1 |
17,2 %1 |
11,8 %1 |
|
week 8 |
69,8 % |
62,5 %1 |
40,1 %1 |
22,8 %1 |
1 Statistically less effective than Daivobet gel (p < 0,001)
The efficacy of Daivobet gel used once daily on the body (excluding the scalp) was evaluated in one randomised, double-blind clinical study of 8 weeks that included 296 patients with mild or moderate plaque psoriasis according to the IGA. Comparators were betamethasone dipropionate in gel vehicle, calcipotriol in gel vehicle and gel vehicle alone, all used once daily. The primary response criteria were disease controlled according to IGA at week 4 and week 8. Disease controlled was defined as 'cleared' or 'minimal' for patients with moderate disease at T0 or 'cleared' for patients with mild disease at T0.
The secondary response criteria were the percentage change in the Psoriasis Severity and Area Index (PASI) between T0 and week 4 and between T0 and week 8.
|
% of patients with controlled disease |
Daivobet gel
|
Betamethasone dipropionate
|
Calcipotriol
|
Gel vehicle
|
|
week 4 |
20,6 % |
10,3 %1 |
4,5 %1 |
2,9 %1 |
|
week 8 |
31,7 % |
19,1 %1 |
13,4 %1 |
0,0 %1 |
1 Statistically less effective than Daivobet gel (p < 0,05)
|
Mean percentage reduction in PASI (SD) |
Daivobet gel
|
Betamethasone dipropionate
|
Calcipotriol
|
Gel vehicle
|
|
week 4 |
50,2 (32,7) |
40,8 (33,3)1 |
32,1 (23,6)1 |
17,0 (31,8)1 |
|
week 8 |
58,8 (32,4) |
51,8 (35,0) |
40,8 (31,9)1 |
11,1 (29,5)1 |
1 Statistically less effective than Daivobet gel (p < 0,05)
Another randomised, single-blind clinical study including 312 patients with scalp psoriasis of at least moderate severity according to the IGA investigated the use of Daivobet gel once daily compared with Daivonex scalp solution twice daily for 8 weeks. Results for the primary endpoint (absence of disease or very mild disease according to the IGA at week 8) showed that Daivobet gel was statistically more effective than Daivonex scalp solution.
|
% of patients with clear or almost clear disease |
Daivobet gel
|
Daivonex
|
|
week 8 |
68,6 % |
31,4 %1 |
1 Statistically less effective than Daivobet gel (p < 0,001)
A randomised, double-blind, long-term clinical study including 873 patients with scalp psoriasis of at least moderate severity at inclusion (according to the IGA) investigated the use of Daivobet gel compared with calcipotriol in the gel vehicle. Both treatments were applied once daily, intermittently as needed, for up to 52 weeks. Adverse effects possibly related to long-term use of corticosteroids on the scalp were identified in a blinded manner by an independent panel of dermatologists. There was no difference in the percentage of patients with such adverse effects between the treatment groups (2,6% in the Daivobet gel group and 3,0% in the calcipotriol group; p = 0,73). No cases of skin atrophy were reported.
Paediatric population
Effects on calcium metabolism were studied in 2 uncontrolled open studies of 8 weeks including a total of 109 adolescents aged 12 to 17 years with scalp psoriasis, who used up to 69 g per week of Daivobet gel. No cases of hypercalcaemia and no clinically relevant changes in calciuria were reported. The adrenal response to ACTH administration was measured in 30 patients; one patient showed a slight decrease in cortisol level on ACTH administration after 4 weeks of treatment, without clinical manifestation and reversible.
Pharmacokinetics
Systemic exposure to calcipotriol and betamethasone dipropionate due to topical application of Daivobet gel is comparable to that of Daivobet ointment in rats and guinea pigs. Clinical studies with radiolabelled ointment have shown that systemic absorption of calcipotriol and betamethasone from Daivobet formulated as ointment is less than 1% of the dose (2,5 g) when applied to healthy skin (625 cm2) for 12 hours. Application to psoriatic plaques and under occlusive dressings may increase absorption of topical corticosteroids. Absorption through damaged skin is approximately 24%.
Following systemic exposure, both active substances - calcipotriol and betamethasone dipropionate - are rapidly and extensively metabolised. Protein binding is approximately 64%. The plasma elimination half-life after intravenous administration is 5-6 hours. Due to the formation of a depot in the skin, elimination after cutaneous application is on the order of a few days. Betamethasone is metabolised mainly by the liver, but also by the kidneys into glucuronides and sulphate esters. Calcipotriol is excreted via the faeces (rats and guinea pigs) and betamethasone dipropionate via the urine (rats and mice). In rats, tissue distribution studies of radiolabelled calcipotriol and betamethasone dipropionate showed that the kidney and liver had, respectively, the highest levels of radioactivity.
Calcipotriol and betamethasone dipropionate were below the lower limit of quantification in all blood samples from 34 patients treated for 4 or 8 weeks with both Daivobet gel and Daivobet ointment for extensive body and scalp psoriasis. A metabolite of calcipotriol and a metabolite of betamethasone dipropionate were quantifiable in some of the patients.
Preclinical safety
Studies with corticosteroids in animals have shown embryotoxicity (cleft palate, skeletal malformations). In reproductive function studies in rats after long-term oral administration of corticosteroids, prolonged gestation and prolonged, difficult labour were observed. In addition, decreased survival, body weight and weight gain of the offspring were observed. Fertility was not impaired. The relevance of these data for humans is not known.
A dermal carcinogenicity study in mice and an oral carcinogenicity study in rats did not reveal any particular risks of calcipotriol for humans.
Photo(co)carcinogenicity studies in mice suggest that calcipotriol may increase the skin tumour-inducing effect of UV radiation.
A dermal carcinogenicity study in mice and an oral carcinogenicity study in rats did not show any particular risks of betamethasone dipropionate for humans. No photocarcinogenicity study has been conducted with betamethasone dipropionate.
In local tolerance studies in rabbits, Daivobet gel caused mild to moderate skin irritation and mild, transient eye irritation.
INCOMPATIBILITIES
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Shelf life
3 years.
Vial : After first opening: 6 months.
Applicator : After first opening: 6 months.
Special storage precautions
Do not refrigerate.
Vial : Keep in the outer packaging, protected from light.
SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Prescription, supply and reimbursement
| Marketing authorisation (AMM) |
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| Price: |
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Collection.
IMMEUBLE AMPERE E + LA DÉFENSE 34-40 RUE HENRI REGNAULT
92400 COURBEVOIE-LA-DÉFENSE
Tél : 01 30 14 40 00 leo.group@leo-pharma.com
https://www.leo-pharma.fr/
Source: VIDAL · Updated on 10/11/2026. This information does not replace advice from a healthcare professional.