Daivobet^® (Ointment) Instructions for Use

Marketing Authorization Holder

Leo Pharma, A/S (Denmark)

Manufactured By

LEO Laboratories, Limited (Ireland)

ATC Code

D05AX52 (Calcipotriol in combination with other preparations)

Active Substances

Calcipotriol (Rec.INN registered by WHO)

Betamethasone (Rec.INN registered by WHO)

Dosage Form

Daivobet®

Ointment for external use 500 mcg+50 mcg/1 g: tubes 15 g, 30 g, or 60 g

Dosage Form, Packaging, and Composition

Ointment for external use is homogeneous, semi-transparent, ranging from almost white to yellow in color.

Excipients: liquid paraffin (contains about 10 ppm alpha-tocopherol) – 30 mg, polyoxypropylene stearyl ether (contains about 0.1% butylated hydroxytoluene) – 50 mg, alpha-tocopherol – 0.02 mg, soft white paraffin (contains about 10 ppm alpha-tocopherol) – up to 1000 mg.

15 g – aluminum tubes (1) – cardboard packs.
30 g – aluminum tubes (1) – cardboard packs.
60 g – aluminum tubes (1) – cardboard packs.

Clinical-Pharmacological Group

A drug with antiproliferative and anti-inflammatory action for the treatment of psoriasis

Pharmacotherapeutic Group

Antipsoriatic agents; topical antipsoriatic agents; other topical antipsoriatic agents

Pharmacological Action

A combined medicinal product for external use.

Calcipotriol is a synthetic analogue of the active metabolite of vitamin D. It inhibits the proliferation of keratinocytes and accelerates their morphological differentiation.

Betamethasone is a topical glucocorticosteroid; it exerts local anti-inflammatory, antipruritic, vasoconstrictive, and immunosuppressive effects, however, the precise mechanisms of the anti-inflammatory action of topical steroids are not fully understood.

Pharmacokinetics

When applied topically, the absorption of calcipotriol and betamethasone through intact skin is less than 1%.

Application to psoriatic plaques and under occlusive dressings increases the absorption of betamethasone. Since a depot of the drug is created in the skin, its elimination from the skin occurs over several days. Betamethasone is metabolized in the liver and kidneys to form glucuronides and sulfate esters. It is excreted via the intestines and kidneys.

Indications

Chronic vulgar plaque psoriasis.

Scalp psoriasis; psoriasis of mild to moderate severity of other parts of the body.

ICD codes

Dosage Regimen

Apply a thin layer of ointment to the affected skin areas once daily. Rub in gently and completely.

The maximum daily dose is 15 grams. The maximum weekly dose must not exceed 100 grams.

Treatment duration is generally up to 4 weeks for body plaques and up to 8 weeks for scalp psoriasis, unless otherwise directed.

Do not apply to the face, scalp, axillae, groin, or other intertriginous areas unless specifically instructed. Avoid application to mucous membranes and the periorbital area.

Discontinue use once the plaques have cleared. Do not use for maintenance therapy.

Monitor for signs of skin atrophy, especially with prolonged use. If irritation develops, discontinue treatment.

Adverse Reactions

Skin and skin appendages: frequent – itching, rash, burning sensation; infrequent – pain, irritation, dermatitis, erythema, exacerbation of psoriasis, pigmentation disorder at the site of ointment application, folliculitis; rare – pustular psoriasis.

Calcipotriol may cause local skin irritation, itching, burning, acute pain, dry skin, erythema, rash, dermatitis, eczema, and exacerbation of psoriasis.

With long-term external use of betamethasone, the development of skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation, colloid degeneration of the skin, as well as an increased risk of developing generalized pustular psoriasis, hyper- and photosensitivity reactions are possible.

Systemic reactions: associated with the use of calcipotriol (very rare): hypercalcemia or hypercalciuria. With long-term use of topical glucocorticosteroids in high doses, suppression of adrenal function with the development of secondary adrenal insufficiency and symptoms of hypercortisolism, including Cushing’s syndrome, is possible.

Contraindications

Diseases accompanied by impaired calcium metabolism; hypersensitivity to any component of the drug; severe hepatic impairment; severe renal impairment; viral (including herpes or chickenpox), fungal, bacterial, and parasitic skin infections; rosacea; acne rosacea; acne vulgaris; perioral dermatitis; skin manifestations of tuberculosis and syphilis; skin atrophy, skin ulcers; increased fragility of skin vessels; ichthyosis; perianal and genital itching; psoriatic erythroderma; guttate, exfoliative, pustular psoriasis.

Use in Pregnancy and Lactation

Should be used only when the potential benefit to the mother outweighs the risk to the fetus or child.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment.

Use in Renal Impairment

Contraindication: severe renal impairment.

Pediatric Use

Experience of use in children under 18 years of age is absent.

Special Precautions

It is not recommended to apply to mucous membranes. Do not apply to the periorbital area due to the possible development of cataracts and increased intraocular pressure.

The risk of developing hypercalcemia when following the recommended dosage regimen is minimal. However, when used in doses exceeding the recommended maximum weekly dose (100 g), hypercalcemia may develop, which quickly resolves upon dose reduction or discontinuation.

The drug contains a potent glucocorticosteroid, therefore concomitant treatment with other glucocorticosteroids is not recommended.

It is recommended to avoid application to extensive skin areas constituting more than 30% of the body surface area, as well as under occlusive dressings, and application to skin folds, as this increases the likelihood of systemic absorption of the glucocorticosteroid and the development of systemic adverse reactions.

Adverse effects such as suppression of the hypothalamic-pituitary-adrenal system with the development of reversible secondary adrenal insufficiency or exacerbation of diabetes mellitus, associated with systemic administration of glucocorticosteroids, can also be observed with long-term use of topical glucocorticosteroids, due to systemic absorption. If psoriasis is complicated by a secondary infection, antibacterial therapy should be administered, and if the infection worsens, the drug should be discontinued.

During treatment, limit or avoid excessive exposure to natural or artificial sunlight. Topical calcipotriol should be used with UV light only if the doctor and patient believe that the potential benefit outweighs the potential risks.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.