Daivobet ointment 30 g

Instructions for Daivobet ointment 30 g

Composition

active ingredients: betamethasone; calcipotriol;

1 g of ointment contains 0.643 mg of betamethasone dipropionate, corresponding to 0.5 mg of betamethasone and 52.2 μg of calcipotriol monohydrate, corresponding to 50 μg of calcipotriol;

excipients: mineral oil, polyoxypropylene stearyl ether, alpha-tocopherol, white soft paraffin, butylhydroxytoluene (E 321).

Dosage form

Ointment.

Main physicochemical properties: homogeneous ointment from almost white to yellow.

Pharmacotherapeutic group

Topical antipsoriatic agents. Other topical antipsoriatic agents. Calcipotriol, combinations.

ATX code D05A X52.

Pharmacological properties

Pharmacodynamics

Calcipotriol is a vitamin D analogue. In vitro data indicate that calcipotriol inhibits keratinocyte proliferation and accelerates their morphological differentiation. This is the proposed mechanism for its effect in psoriasis.

Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory, antipruritic, vasoconstrictor and immunosuppressive effects, but does not eliminate the root cause of the disease. The use of occlusive dressings enhances the therapeutic effect by increasing penetration into the stratum corneum of the epidermis. In this regard, the frequency of adverse reactions may increase. In general, the mechanism of anti-inflammatory activity of topical steroids has not been fully elucidated.

A safety study in 634 patients with psoriasis investigated repeated courses of Daivobet ointment applied once daily as needed either as monotherapy or alternating with Dovonex for up to 52 weeks compared to Dovonex as monotherapy for 48 weeks after the initial course of Daivobet ointment. Adverse drug reactions were reported in 21.7% of patients in the Daivobet ointment group, 29.6% of patients in the Daivobet ointment alternating with Dovonex group, and 37.9% of patients in the Dovonex group. Adverse drug reactions reported in more than 2% of patients in the Daivobet ointment group were pruritus (5.8%) and psoriasis (5.3%). Adverse drug reactions of interest possibly related to long-term corticosteroid use (e.g. skin atrophy, folliculitis, depigmentation, furuncles and purpura) were reported in 4.8% of patients in the Daivobet ointment group, 2.8% of patients in the Daivobet/Dovonex alternating ointment group, and 2.9% of patients in the Dovonex group.

The adrenal response to adrenocorticotropic hormone (ACTH) was assessed by measuring serum cortisol levels in patients with widespread psoriasis of both the scalp and other body areas using up to 106 g of the combination of Daivobet gel and Daivobet ointment per week. A marginal decrease in cortisol excretion in response to ACTH stimulation 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, serum cortisol levels were within normal limits 60 minutes after ACTH stimulation. There was no evidence of altered calcium metabolism in these patients. Thus, with regard to suppression of the hypothalamic-pituitary-adrenal axis, this study provided some evidence that very high doses of Daivobet gel and ointment may have a weak effect on hypothalamic-pituitary-adrenal axis function.

Pediatric patients

The adrenal response to ACTH stimulation was evaluated in an uncontrolled 4-week study in 33 adolescents aged 12-17 years with psoriasis of the body who used up to 56 g of Daivobet ointment per week. There were no reports of hypothalamic-pituitary-adrenal axis suppression. No cases of hypercalcemia were reported, but one patient had an increase in urinary calcium levels, possibly related to treatment.

Pharmacokinetics

After systemic exposure, both active ingredients, calcipotriol and betamethasone dipropionate, are rapidly and extensively metabolized. The drug is approximately 64% protein bound. The plasma half-life of the drug after intravenous administration is 5–6 hours. Due to the formation of a depot in the skin, elimination of the drug from the skin after cutaneous application occurs within several days. Betamethasone is metabolized mainly in the liver, but also in the kidneys with the formation of glucuronides and sulfoesters. The main route of excretion of calcipotriol is with feces (in rats and minipigs), and of betamethasone dipropionate is with urine (in rats and mice). In rats, tissue distribution studies of radiolabeled calcipotriol and betamethasone dipropionate demonstrated that the kidneys and liver had the highest levels of radioactivity.

Calcipotriol and betamethasone dipropionate levels were below the lower limit of quantification in all blood samples from 34 patients treated for 4 or 8 weeks with either Daivobet gel or Daivobet ointment for widespread psoriasis on both the body and scalp. One metabolite of calcipotriol and one metabolite of betamethasone dipropionate were quantifiable in some patients.

Indication

Topical treatment of stable plaque psoriasis vulgaris responsive to topical therapy in adults.

Contraindication

Hypersensitivity to the active substances or to any of the excipients of the medicinal product.

The use of the drug Daivobet is contraindicated in patients with psoriatic erythroderma, exfoliative and pustular psoriasis.

Due to the content of calcipotriol, Daivobet is contraindicated in patients with known disorders of calcium metabolism (see section "Special warnings and precautions for use").

Due to the corticosteroid content, Daivobet is contraindicated in the following diseases: skin lesions of viral etiology (e.g. herpes or chickenpox), fungal, bacterial and parasitic skin infections, skin manifestations of tuberculosis, perioral dermatitis, skin atrophy, atrophic skin stripes, increased vascular fragility, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds (see the section "Special instructions for use").

Interaction with other medicinal products and other types of interactions

No drug interaction studies have been conducted with Daivobet.

Application features

Impact on the endocrine system

Daivobet ointment contains a potent Group III steroid. Concomitant treatment with other steroids should be avoided. Adverse reactions that develop in connection with treatment with systemic corticosteroids, such as suppression of adrenal function or effects on the metabolic control of diabetes mellitus, may also develop during treatment with topical corticosteroids, due to systemic absorption.

Application under occlusive dressings should be avoided as this increases systemic absorption of corticosteroids. Application to large areas of damaged skin or mucous membranes or in skin folds should be avoided as this increases systemic absorption of corticosteroids (see section "Adverse reactions").

In a study of patients with both widespread scalp psoriasis and widespread psoriasis of other body areas using a combination of Daivobet gel at high doses (application of the drug to the scalp) and Daivobet ointment at high doses (application of the drug to other body areas), a marginal decrease in cortisol excretion in response to ACTH stimulation was observed in 5 of 32 patients after 4 weeks of treatment (see section "Pharmacodynamics").

Effect on calcium metabolism

Due to the content of calcipotriol, hypercalcemia may develop if the maximum daily dose (15 g) is exceeded. Serum calcium levels return to normal upon discontinuation of treatment. The risk of hypercalcemia is minimal if the recommendations for calcipotriol are followed. The drug should not be applied to skin areas exceeding 30% of the body surface (see section "Method of administration and dosage").

Local adverse reactions

Daivobet contains a potent Group III steroid. Concomitant treatment with other steroids at the same site should be avoided. The skin of the face and genitals is very sensitive to corticosteroids. The drug should not be used on these sites. The patient should be instructed on the correct use of the drug to prevent application or accidental contact with the face, mouth and eyes. Hands should be washed after each application of the drug to prevent accidental contact with these areas of the body.

Concomitant skin infections

If the lesions are complicated by secondary infection, antibacterial therapy should be administered. However, if the infection worsens, corticosteroid treatment should be discontinued (see Contraindications).

When treating psoriasis with topical corticosteroids, there is a risk of generalized pustular psoriasis or rebound effects upon drug withdrawal. Therefore, continued medical supervision is necessary after discontinuation of drug treatment.

Long-term use of the drug

The risk of local or systemic adverse reactions increases with long-term use of corticosteroids. Treatment with the drug should be discontinued if adverse reactions associated with long-term use of corticosteroids occur (see section "Adverse reactions").

Application not evaluated

There is no experience with the use of Daivobet in patients with guttate psoriasis.

Concomitant treatment and UV irradiation

To date, there are only limited data on the use of this medicinal product on the scalp. Daivobet ointment has been used in combination with Daivobet gel for the treatment of psoriatic lesions on the body, but there is limited experience with the combination of Daivobet with other topical antipsoriatic medicinal products on the same area, with other systemic antipsoriatic medicinal products, or with phototherapy.

During treatment with Daivobet, patients are advised to limit or avoid excessive exposure to natural or artificial light. Topical calcipotriol should not be used with UVA unless the physician and patient consider that the expected benefit outweighs the potential risk.

Adverse reactions to excipients

Daivobet ointment contains butylhydroxytoluene (E 321) as an excipient, which may cause local skin reactions (e.g. contact dermatitis) or irritation of the eyes and mucous membranes.

Use during pregnancy or breastfeeding

Pregnancy

There are no adequate data on the use of Daivobet in pregnant women. Animal studies with glucocorticosteroids have shown reproductive toxicity, but a number of epidemiological studies (less than 300 pregnancy outcomes) have not revealed any congenital anomalies in infants born to mothers exposed to corticosteroids during pregnancy. The potential risk to humans has not yet been determined. Therefore, Daivobet should be used during pregnancy only if the expected benefit outweighs the potential risk.

Breast-feeding

Betamethasone passes into breast milk, but adverse reactions in the child are unlikely when using the drug in therapeutic doses. There are no clinical data on the excretion of calcipotriol into breast milk. Daivobet should be prescribed with caution to women during breastfeeding. Patients should not apply Daivobet to the mammary glands while breastfeeding.

Fertility

Studies in rats with oral administration of calcipotriol or betamethasone dipropionate did not reveal any reduction in male or female fertility.

Ability to influence reaction speed when driving vehicles or other mechanisms

The effect of the drug Daivobet on the ability to drive vehicles or operate other mechanisms is absent or insignificant.

Method of administration and doses

Daivobet ointment should be applied to the affected skin areas once a day. The recommended treatment period is 4 weeks. There is experience with repeated courses of Daivobet for up to 52 weeks. If after 4 weeks it is necessary to continue or resume treatment with the drug, the drug should be continued after consultation with a doctor and under regular medical supervision.

When using medicinal products containing calcipotriol, the maximum daily dose should not exceed 15 g. The area of application of medicinal products containing calcipotriol should not exceed 30% of the body surface (see section "Special instructions").

Special patient groups

Patients with renal and hepatic impairment

The safety and efficacy of Daivobet ointment in patients with severe renal insufficiency or severe liver disease have not been established.

Method of application

Daivobet ointment should be applied to the affected areas of the skin. It is not recommended to take a shower or bath immediately after applying Daivobet to achieve optimal effect.

Children.

Pediatric patients

The safety and efficacy of Daivobet ointment in children (under 18 years of age) have not been established. Currently available data on the use of the medicinal product in children aged 12 to 17 years are described in the sections “Pharmacodynamics” and “Adverse reactions”, but no dosage recommendations can be made.

Overdose

Excessive prolonged use of topical corticosteroids may suppress pituitary-adrenal function with the development of secondary adrenal insufficiency, which is usually reversible. In such cases, symptomatic treatment is indicated.

In case of chronic toxicity, corticosteroids should be gradually withdrawn.

It has been reported that, as a result of incorrect use of the medicinal product, one patient with widespread erythrodermic psoriasis, who was treated with 240 g of Daivobet ointment weekly (corresponding to a daily dose of approximately 34 g) for 5 months (the maximum recommended dose is 15 g per day), developed Cushing's syndrome during treatment and subsequently pustular psoriasis after abrupt discontinuation of treatment.

Side effects

The assessment of the frequency of adverse reactions is based on a generalized analysis of clinical trial data, including post-marketing safety studies and spontaneous reports.

The most commonly reported adverse reactions during treatment are various skin reactions such as itching and peeling of the skin.

Cases of pustular psoriasis and hypercalcemia have been reported.

Adverse reactions are listed according to MedDRA system organ class (SOC) and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Very common (≥ 1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

*Skin infections, including bacterial, fungal, and viral skin infections, have been reported.

**Various types of rashes have been reported, such as exfoliative rash, papular rash, and pustular rash.

***Burning sensation at the site of application of the drug is included in application site pain.

Pediatric patients

In an uncontrolled open-label study, 33 adolescents aged 12–17 years with psoriasis vulgaris were treated with Daivobet ointment for 4 weeks up to a maximum dose of 56 g per week. No new adverse events or any concerns regarding systemic corticosteroid effects were identified. However, the size of this study does not allow for definitive conclusions regarding the safety profile of Daivobet ointment when used in children.

The adverse reactions listed below are considered to be related to the pharmacological classes of calcipotriol and betamethasone, respectively.

Calcipotriol

Side effects include application site reactions, itching, skin irritation, burning and stinging sensations, dry skin, erythema, rash, dermatitis, eczema, exacerbation of psoriasis, photosensitivity and hypersensitivity reactions, which may include in very rare cases angioedema and facial swelling.

Very rarely, systemic reactions may occur after topical application, leading to hypercalcemia or hypercalciuria (see section "Special warnings and precautions for use").

Betamethasone (as dipropionate)

After topical application, reactions at the application site may develop, especially during prolonged use, including the development of skin atrophy, telangiectasias, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid degeneration of the skin. When treating psoriasis with topical corticosteroids, there may be a risk of developing generalized pustular psoriasis.

Systemic reactions associated with topical corticosteroids are rare in adults. However, they may be severe. Adrenal suppression, cataracts, infections, effects on metabolic control of diabetes mellitus, and increased intraocular pressure may occur, especially after long-term treatment with the drug. Systemic reactions are more common when occlusive dressings (plastic, skin folds) are used, when the drug is applied to large areas, and during long-term treatment (see section "Special instructions").

Expiration date

2 years.

After first opening – 1 year.

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Packaging

15 g or 30 g of ointment in a tube. 1 tube in a cardboard box.

Vacation category

Without a prescription.

Producer

LEO Laboratories Limited.

Location of the manufacturer and address of its place of business.

285 Cashel Road, Crumlin, Dublin 12, Ireland.

Address

285 Cashel Road, Crumlin, Dublin 12, Ireland.