Daivobet

Daivobet

betamethasone + calcipotriol

Manufacturer:

LEO Pharma

Distributor:

Getz Bros
Full Prescribing Info
Contents
Calcipotriol monohydrate, betamethasone dipropionate.
Description
Each gram of Daivobet ointment and gel contains calcipotriol (as monohydrate) 50 mcg and betamethasone (as dipropionate) 500 mcg.
Action
Pharmacology: Pharmacodynamics: Calcipotriol is a vitamin D analogue. In vitro data suggest that calcipotriol induces differentiation and suppresses proliferation of keratinocytes. This is the proposed basis for its effect in psoriasis.
Gel: Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory, antipruritic, vasoconstrictive and immunosuppresive properties, however, without curing the underlying condition. Through occlusion, the effect can be enhanced due to increased penetration of the stratum corneum. The incidence of adverse events will increase because of this. In general, the mechanism of the anti-inflammatory activity of the topical steroids is unclear.
Pharmacokinetics: Gel: The human transdermal absorption of calcipotrol and betamethasone, respectively, has been shown to be <1% of the administered dose for both substances. The systemic absorption under normal conditions of use is not expected to have any influence on systemic parameters. The pharmacokinetic behavior for the 2 active constituents is not influenced by the presence of each other.
The systemic exposure to calcipotriol and betamethasone dipropionate from topically applied Daivobet gel is comparable to Daivobet ointment in rats and minipigs.
Clinical studies with radiolabelled ointment indicate that the systemic absorption of calcipotriol and betamethasone from Daivobet ointment formulation is <1% of the dose (2.5 g) when applied to normal skin (625 cm2) for 12 hrs. Application to psoriasis plaques and under occlusive dressings may increase the absorption of topical corticosteroids.
Following systemic exposure, both active ingredients, calcipotriol and betamethasone dipropionate, are rapidly and extensively metabolised. The main route of excretion of calcipotriol is via feces (rats and minipigs) and for betamethasone dipropionate it is via urine (rats and mice).
Calcipotriol and betamethasone dipropionate were below the lower limit of quantification in all blood samples of 34 patients treated for 4 or 8 weeks with both Daivobet gel and Daivobet ointment for extensive psoriasis involving the body and scalp. One (1) metabolite of calcipotriol and 1 metabolite of betamethasone dipropionate were quantifiable in some of the patients.
Indications/Uses
Ointment: Management of psoriasis vulgaris.
Gel: Topical treatment of mild to moderate 'non-scalp' plaque psoriasis vulgaris.
Dosage/Direction for Use
Gel: Daivobet should be applied to the affected area once daily. The recommended treatment duration is 4 weeks. After this period, repeated treatment with Daivobet can be initiated under medical supervision. The maximum daily dose should not exceed 15 g, the maximum weekly dose should not exceed 100 g and the treated area should not be >30% of the body surface area.
Daivobet gel should be applied to affected areas of the scalp once daily. The recommended treatment period is 8 weeks for non-scalp areas. After this period repeated treatment with Daivobet gel can be initiated under medical supervision.
All the affected scalp areas may be treated with Daivobet gel. Usually an amount between 1 g and 4 g daily is sufficient for treatment of the scalp (4 g corresponds to 1 teaspoon).
When using calcipotriol containing products, the maximum daily dose should not exceed 15 g, and the maximum weekly dose should not exceed 100 g. The body surface area (BDA) treated with calcipotriol containing products should not exceed 30%.
Administration: Gel: Shake the bottle before use. In order to achieve optimal effect, it is recommended that the hair is not washed immediately after application of Daivobet gel. Daivobet gel should remain on the skin during the night or during the day.
Overdosage
Use above the recommended dose may cause elevated serum calcium which should rapidly subside when treatment is discontinued. Excessive prolonged use of topical corticosteroids may suppress the pituitary-adrenal functions, resulting in secondary adrenal insufficiency which is usually reversible. In such cases, symptomatic treatment is indicated.
In case of chronic toxicity, the corticosteroid treatment must be discontinued gradually. It has been reported that due to misuse, 1 patient with extensive erythrodermic psoriasis treated with 240 g of Daivobet ointment weekly (maximum dose 100 g weekly) for 5 months developed Cushing's syndrome and pustular psoriasis after abruptly stopping treatment.
Contraindications
Hypersensitivity to calcipotriol monohydrate or betamethasone dipropionate gel or to any of the excipients of Daivobet.
Due to the content of calcipotriol, Daivobet gel is contraindicated in patients with known disorders of calcium metabolism.
Due to the content of corticosteroid, Daivobet gel is contraindicated in the following conditions: Viral (eg, herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis or syphilis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds.
Daivobet gel is contraindicated in guttate, erythrodermic, exfoliative and pustular psoriasis. It is also contraindicated in patients with severe renal insufficiency or severe hepatic disorders.
Special Precautions
Daivobet gel contains a potent group III steroid and concurrent treatment with other steroids on the scalp must be avoided. Adverse effects found in connection with systemic corticosteroid treatment, eg, adrenocortical suppression or impact on the metabolic control of diabetes mellitus, may occur also during topical corticosteroid treatment due to systemic absorption. Application under occlusive dressings should be avoided since it increases the systemic absorption of corticosteroids.
In a study in patients with both extensive scalp and extensive body psoriasis using a combination of high doses of Daivobet gel (scalp application) and high doses of Daivobet ointment (body application), 5 of 32 patients showed a borderline decrease in cortisol response to adrenocorticotropic hormone (ACTH) challenge after 4 weeks of treatment. Due to the content of calcipotriol, hypercalcaemia may occur if the maximum weekly dose (100 g) is exceeded. Serum calcium is, however, quickly normalised when treatment is discontinued. The risk of hypercalcemia is minimal when the recommendations relevant to calcipotriol are followed.
Treatment of >30% of the body surface should be avoided. Application on large areas of damaged skin or on mucous membranes or in skin folds should be avoided since it increases the systemic absorption of corticosteroids. Skin of the face and genitals are very sensitive to corticosteroids. These areas should only be treated with weaker corticosteroids.
Uncommon local adverse reactions (eg, eye irritation or irritation of facial skin) were observed, when the drug was accidentally administered in the area of face, or accidentally to the eyes or conjunctives. The patient must be instructed in correct use of the product to avoid application and accidental transfer to the face, mouth and eyes. Hands must be washed after each application to avoid accidental transfer to these areas.
When lesions become secondarily infected, they should be treated with antimicrobiological therapy. However, if infection worsens, treatment with corticosteroids should be discontinued. When treating psoriasis with topical corticosteroids, there may be a risk of generalised pustular psoriasis or of rebound effects when discontinuing treatment. Medical supervision should therefore continue in the post-treatment period.
With long-term use, there is an increased risk of local and systemic corticosteroid undesirable effects.
The treatment should be discontinued in case of undesirable effects related to long-term use of corticosteroid.
There is no experience with concurrent use of other anti-psoriatic products administered systemically or with phototherapy. During Daivobet gel treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Topical calcipotriol should be used with UVR only if the physician and patient consider that the potential benefits outweigh the potential risks. Daivobet gel contains butylated hydroxytoluene (E321), which may cause local skin reactions (eg, contact dermatitis), or irritation to the eyes and mucous membranes.
Use in pregnancy: There are no adequate data from the use of Daivobet gel in pregnant women. Studies in animals with glucocorticoids have shown reproductive toxicity but a number of epidemiological studies have not revealed congenital anomalies among infants born to women treated with corticosteroids during pregnancy. The potential risk for humans is uncertain. Therefore, during pregnancy, Daivobet gel should only be used when the potential benefit justifies the potential risk.
Use in lactation: Betamethasone passes into breast milk, but risk of an adverse effect on the infant seems unlikely with therapeutic doses. There are no data on the excretion of calcipotriol in breast milk. Caution should be exercised when prescribing Daivobet gel to women who breastfeed.
Use in children: Daivobet gel is not recommended for use in children <18 years due to lack of data on safety and efficacy.
Use In Pregnancy & Lactation
Use in pregnancy: There are no adequate data from the use of Daivobet gel in pregnant women. Studies in animals with glucocorticoids have shown reproductive toxicity but a number of epidemiological studies have not revealed congenital anomalies among infants born to women treated with corticosteroids during pregnancy. The potential risk for humans is uncertain. Therefore, during pregnancy, Daivobet gel should only be used when the potential benefit justifies the potential risk.
Use in lactation: Betamethasone passes into breast milk, but risk of an adverse effect on the infant seems unlikely with therapeutic doses. There are no data on the excretion of calcipotriol in breast milk. Caution should be exercised when prescribing Daivobet gel to women who breastfeed.
Adverse Reactions
The clinical trial programme for Daivobet gel has so far included >4,700 patients of whom >2,100 were treated with Daivobet gel. Approximately 8% of patients treated with Daivobet gel experienced a non-serious adverse drug reaction.
Based on data from clinical trials the only known common adverse drug reaction is pruritus. Uncommon adverse drug reactions are burning sensation of skin, skin pain or irritation, folliculitis, dermatitis, erythema, acne, dry skin, exacerbation of psoriasis, rash, pustular rash and eye irritation. These adverse drug reactions were all non-serious local reactions.
The adverse drug reactions are listed by MedDRA system organ class (SOC), and the individual adverse drug reactions are listed starting with the most frequently reported.
Eye Disorders: Uncommon (≥1/1000 and <1/100): Eye irritation.
Skin and Subcutaneous Tissue Disorders: Common (≥1/100 and <1/10): Pruritus. Uncommon (≥1/1,000 and <1/100): Burning sensation of skin, skin pain or irritation, folliculitis, dermatitis, erythema, acne, dry skin, exacerbation of psoriasis, rash, pustular rash.
Adverse drug reactions observed for calcipotriol include application site reactions, pruritus, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, aggravated psoriasis, photosensitivity. Hypersensitivity reactions eg, very rare cases of angioedema and facial edema. Systemic effects after topical use may appear very rarely causing hypercalcemia or hypercalciuria.
Adverse Reactions Observed for betamethasone (as dipropionate): Local reactions can occur after topical use, especially during prolonged application, including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid milia. When treating psoriasis, there may be a risk of generalized pustular psoriasis.
Systemic effects due to topical use of corticosteroids are rare in adults, however, they can be severe. Adrenocortical suppression, cataract, infections and increase of intraocular pressure can occur, especially after long-term treatment. Systemic effects occur more frequently when applied under occlusion (plastic, skin folds), when applied on large areas and during long-term treatment.
Drug Interactions
No interaction studies have been performed.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Do not store above 30°C. Protect from light.
Can be used for 3 months after opening. Do not refrigerate.
ATC Classification
D05AX52 - calcipotriol, combinations ; Belongs to the class of other antipsoriatics for topical use.
Presentation/Packing
Oint 15 g, 30 g. Gel 15 g, 30 g, 60 g.
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