Betliben®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Betliben®

Composition:

Active substance: betamethasone;

1 g of cream contains 0.5 mg of betamethasone in the form of betamethasone dipropionate;

Excipients: white soft paraffin; macrogol cetostearyl ether; cetostearyl alcohol; propylene glycol; mineral oil; methylparahydroxybenzoate (E 218); propylparahydroxybenzoate (E 216); disodium edetate; sodium dihydrogen phosphate dihydrate; sodium hydrogen phosphate dihydrate; purified water.

Pharmaceutical form. 0.05% cream.

Main physicochemical characteristics: white homogeneous cream.

Pharmacotherapeutic group.

Corticosteroids for dermatological use. Potent corticosteroids (Group III).

ATC code D07AC01.

Pharmacological properties.

Pharmacodynamics.

Betamethasone dipropionate is a synthetic adrenocorticosteroid for topical use in dermatology. It is a prednisolone analogue exhibiting a high degree of corticosteroid activity with absent or minimal mineralocorticoid effect. Anti-inflammatory action is the main therapeutic effect of betamethasone.

Betamethasone reduces the formation and release of various inflammatory mediators such as kinins, histamine, lysosomal enzymes, prostaglandins, leukotrienes, and complement components. The anti-inflammatory action of corticosteroids, including betamethasone, is due to inhibition of phospholipase A2. As a result, levels of arachidonic acid, a precursor of prostaglandins and leukotrienes, are reduced. Corticosteroids inhibit migration of leukocytes and macrophages and reduce vascular permeability and vasodilation to such an extent that extravasation of blood serum, as well as edema and pruritus, are diminished. They suppress chemotaxis at the site of inflammation. These effects are nonspecific and therefore occur in inflammation of various origins (mechanical, infectious, or immunological). Due to their immunosuppressive action, corticosteroids may alter the clinical presentation of diseases in which hypersensitivity plays an important role. They inhibit lymphocyte proliferation and antibody production. Corticosteroids also exhibit antifungal activity against human epidermal cells. Their efficacy in psoriasis (psoriatic dermatitis) is explained by this fact. Topically applied corticosteroids such as betamethasone are effective in the treatment of certain dermatoses due to their anti-inflammatory, antipruritic, and vasoconstrictive actions. Systemic absorption may lead to systemic adverse effects such as fluid retention, hypertension, suppression of adrenal gland function, and peptic ulceration.

Pharmacokinetics.

Betamethasone is absorbed through the skin depending on the applied dose and the extent of damage to the stratum corneum. It is believed that no more than 5% of the applied dose is absorbed. Absorbed betamethasone is metabolized in the liver via hydrolysis and oxidation and is excreted by the kidneys. Greater penetration and absorption occur through mucous membranes and damaged skin (inflammation and/or other skin diseases).

Plasma protein binding is 64%. The elimination half-life is 6.5 hours. Less than 5% of the betamethasone concentration in serum is excreted unchanged in urine. Significantly greater absorption occurs under occlusive dressings due to increased local temperature and humidity.

Clinical characteristics.

Indications.

Treatment of skin disorders amenable to corticosteroid therapy:

eczemas and dermatitis of various etiologies, including atopic eczema, solar dermatitis, lichen planus, simple lichen, nodular prurigo, discoid lupus erythematosus, necrobiosis lipoidica and erythroderma, scalp psoriasis and chronic plaque psoriasis on the skin areas of hands and feet, except for widespread plaque psoriasis.

Contraindications.

Hypersensitivity reaction to betamethasone dipropionate or to any of the excipients contained in the medicinal product, rosacea, acne, perioral dermatitis, perianal and genital pruritus. Contraindications to use also include cutaneous tuberculosis and most viral skin infections, such as herpes simplex, vaccination reactions, varicella (chickenpox). The medicinal product should also not be used in diaper dermatitis, fungal or bacterial skin infections without appropriate antimicrobial therapy, and during the first trimester of pregnancy (see section "Use during pregnancy or lactation").

Interaction with other medicinal products and other forms of interaction.

With topical use, there are no interactions between betamethasone dipropionate and other medicinal products.

Special precautions for use.

Betliben® cream is not intended for ophthalmic use.

Local and systemic adverse effects are typical when using corticosteroids, especially with prolonged use over large areas of damaged skin or skin folds. When applied to the face, treatment should not exceed 5 days. Use under occlusive dressings is not recommended. Particular caution should be exercised when applying Betliben® near the face. Contact of the preparation with eyes or mucous membranes must be avoided. Prolonged treatment and/or application over large skin surfaces should be avoided, as absorption of the active ingredient may occur.

Topical corticosteroids may be harmful in patients with psoriasis for several reasons, including relapses due to development of drug tolerance, risk of generalized pustular psoriasis, and systemic toxicity due to impaired skin barrier function. In such cases, careful patient monitoring is extremely important.

General: Systemic absorption of topical corticosteroids may cause reversible suppression of the hypothalamic-pituitary-adrenal (HPA) axis, which could lead to glucocorticoid insufficiency after discontinuation of treatment. In some patients, signs of Cushing's syndrome may also develop due to absorption of topical corticosteroids during treatment. Patients receiving high-potency topical corticosteroids applied over large body surface areas at high doses should be periodically evaluated for HPA axis suppression. If suppression is detected, withdrawal from the product, reduction in application frequency, or substitution with a less potent corticosteroid should be considered.

Recovery of HPA axis function usually occurs rapidly and completely after discontinuation of the product. Occasionally, signs and symptoms of steroid withdrawal syndrome may occur, requiring additional treatment with systemic corticosteroids.

During treatment with topical corticosteroids, any adverse reactions reported with systemic corticosteroid use may also occur, including lack of response to adrenocorticotropic hormone (ACTH) stimulation, particularly in infants and children. Visual disturbances have been reported with both systemic and topical use of corticosteroids. If a patient develops symptoms such as blurred vision or other visual disturbances, the patient should be referred to an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported after systemic and topical corticosteroid use.

Paediatric patients

Paediatric patients may be more sensitive than adults to local corticosteroid-induced suppression of the HPA axis and to exogenous corticosteroid side effects due to greater absorption resulting from a higher skin surface area to body mass ratio. In paediatric patients treated with topical corticosteroids, suppression of the HPA axis, Cushing's syndrome, and intracranial hypertension have been observed. Signs of adrenal suppression in paediatric patients include impaired linear growth, failure to gain body weight, low plasma cortisol levels, and lack of response to adrenocorticotropic hormone (ACTH) stimulation. Signs of intracranial hypertension include bulging fontanelle, headache, and bilateral optic nerve swelling.

Betliben® contains propylene glycol, which may cause skin irritation.

Betliben® contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may cause allergic reactions (including delayed-type hypersensitivity).

Use during pregnancy or breastfeeding

Contraindicated during the first trimester of pregnancy. Since the safety of topical glucocorticosteroids in pregnant women has not been established, drugs of this class should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown whether topical application of corticosteroids results in sufficient systemic absorption to appear in breast milk. After systemic administration, corticosteroids are excreted into breast milk in amounts unlikely to cause harm to the infant. However, a decision should be made whether to discontinue the drug, taking into account the importance of the drug for the mother.

Ability to affect reaction speed when driving or operating machinery

Has no effect on the ability to drive or operate machinery.

Method of Administration and Dosage

Apply Betliben® cream as a thin layer to the entire affected area of skin once or twice daily, depending on the severity of the condition, and rub in gently with light massage. The method of administration should be adapted according to skin type and stage of the disease. The cream is intended for the treatment of acute, exuding skin lesions. For fissured, scaly, hyperkeratotic skin areas where the cream layer is easily removed by clothing, betamethasone may be applied more than twice daily. The method of administration should be adjusted according to skin type and stage of the disease.

Betamethasone should not be used under occlusive dressings, as this may enhance the risk of adverse reactions. Prolonged use of Betliben® cream or application over large areas (more than 20% of body surface) should be avoided. This also applies to treatment involving more than 10% of body surface for longer than one week.

Once clinical improvement is achieved, it is often recommended to switch to a weaker glucocorticosteroid. Careful monitoring for signs and symptoms of systemic drug effects is advised.

Children

There are no clinical data on the use of this medicinal product in children; therefore, its use is not recommended in this age group. Since children have a higher surface area to body weight ratio compared to adults, absorption of the drug is more pronounced. Children are at greater risk of hypothalamic-pituitary-adrenal (HPA) axis suppression and development of exogenous corticosteroid effects when corticosteroids are used.

Overdose

Excessive and prolonged use of the medicinal product on large skin areas may lead to systemic adverse effects typical of glucocorticosteroids, including suppression of the HPA axis with consequent secondary adrenal insufficiency, and manifestations of hypercortisolism, such as Cushing's syndrome (especially in children).

Treatment: Symptomatic therapy. Electrolyte balance should be corrected if necessary. Gradual withdrawal of the drug is recommended.

Side effects

Systemic absorption of betamethasone may increase when applied over large areas of skin or in skin folds for prolonged periods, or when excessive amounts of corticosteroids are used. In such cases, appropriate precautions are required, especially when treating children.

The following adverse reactions have been reported:

Skin and subcutaneous tissue disorders

Burning, stinging, skin thickening, skin cracking, sensation of warmth, plastic desquamation of the skin, focal desquamation, follicular eruption, erythema, telangiectasia, pruritus, irritation, dry skin, hypertrichosis, acneiform eruptions, hypopigmentation, rosacea-like dermatitis, allergic contact dermatitis, maceration of the skin, miliaria, acne, and tinea incognito due to prolonged steroid use. With long-term continuous use, (local) skin atrophy, striae formation, and dilation of superficial blood vessels (especially on the face) may occur.

Infections and infestations

Secondary infections, folliculitis.

Endocrine system disorders

Adrenal insufficiency.

When the product is applied over large skin areas or under occlusive dressing, especially for prolonged periods, systemic effects of the drug should be considered. Any adverse reactions associated with systemic use of glucocorticoids, including suppression of the adrenal cortex, may also occur with topical application of such medicinal products. Hypersensitivity reactions may occur in individuals with known hypersensitivity to any component of the preparation. Blurred vision has also been reported during corticosteroid use (frequency unknown).

Shelf life: 2 years.

Storage conditions

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

Packaging

25 g or 100 g of cream in a tube; 1 tube in a cardboard box.

Prescription category: Prescription only.

Manufacturer

Jadran-Galenski Laboratorij d.d.

Manufacturer's address and place of business

Svilno 20, 51000 Rijeka, Croatia.