Arelya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ARELIA® (ARELIA)

Composition:

Active substance: fluticasone propionate;

1 g of cream contains 0.5 mg fluticasone propionate;

Excipients: propylene glycol, mineral oil, isopropyl myristate, cetostearyl alcohol, macrogol cetostearyl ether, imidourea, disodium hydrogen phosphate dodecahydrate, citric acid monohydrate, purified water.

Pharmaceutical form. Cream.

Main physicochemical properties: homogeneous soft cream of white or almost white color.

Pharmacotherapeutic group. Corticosteroids for dermatological use. Ordinary corticosteroids. Potent corticosteroids (Group III). Fluticasone.

ATC code D07A C17.

Pharmacological Properties

Pharmacodynamics

Fluticasone propionate is a glucocorticoid drug with high anti-inflammatory activity and a very low level of suppression of the hypothalamic-pituitary-adrenal system when applied topically, resulting in one of the widest therapeutic indices among all currently available topical corticosteroids.

Fluticasone propionate demonstrates high systemic activity after subcutaneous administration but very low activity after oral administration, likely due to metabolic inactivation. In vitro studies have shown its high affinity for human glucocorticoid receptors.

Fluticasone propionate does not exhibit unexpected hormonal effects or significant effects on the central or peripheral nervous systems, gastrointestinal, cardiovascular, or respiratory systems.

Pharmacokinetics

Absorption

Topical and oral administration results in very low bioavailability due to limited drug absorption through the skin or from the gastrointestinal tract, as well as extensive first-pass metabolism. Oral bioavailability approaches zero; therefore, systemic effects of fluticasone propionate following any internal use of the cream will be minimal.

Distribution

Studies have demonstrated that only a very small amount of orally administered fluticasone propionate reaches systemic circulation, which is rapidly eliminated via bile and excreted in feces. Fluticasone propionate does not accumulate in any tissues and does not bind to melanin.

Metabolism

Pharmacokinetic studies in animals indicate that fluticasone propionate is rapidly eliminated and undergoes extensive metabolic clearance. In humans, metabolic clearance is extensive and elimination is rapid. Any drug penetrating the skin into systemic circulation is quickly inactivated. The primary metabolic pathway is hydrolysis to the carboxylic acid metabolite, which has very low glucocorticoid and anti-inflammatory activity.

Excretion

Animal studies indicate that the route of excretion of fluticasone propionate does not depend on the route of administration. It is excreted primarily in feces, and elimination is complete within 48 hours.

Clinical Characteristics

Indications

Adults

Dermatoses responsive to corticosteroid therapy, such as:

• atopic dermatitis;
• nummular dermatitis (discoid eczema);
• lichen simplex chronicus (prurigo nodularis);
• psoriasis (except widespread plaque psoriasis);
• simple chronic lichen (neurodermatitis), lichen planus;
• seborrheic dermatitis;
• irritant or allergic contact dermatitis;
• discoid lupus erythematosus;
• generalized erythroderma (as an adjunctive treatment);
• insect bite reactions;
• erythema toxicum.

Children

Use for treatment of atopic dermatitis in children aged 3 months and older when treatment with less potent corticosteroids has been ineffective.

Contraindications

Hypersensitivity to the active substance or to any component of the medicinal product.

Untreated skin infections.

Rosacea.

Common acne.

Perioral dermatitis.

Perianal and genital pruritus.

Pruritus without inflammation.

Dermatoses in children under 3 months of age, including diaper dermatitis and diaper rash.

Interaction with other medicinal products and other forms of interaction

Concomitant use with medicinal products that may inhibit CYP3A4 (e.g., ritonavir, itraconazole) has been shown to inhibit corticosteroid metabolism, potentially increasing systemic effects. The clinical significance of such an interaction depends on the dose of the medicinal product, the route of administration of the corticosteroid, and the potency of the CYP3A4 inhibitor.

Special precautions for use

Use with caution in patients with a history of local hypersensitivity reactions to corticosteroids or any of the excipients of this medicinal product. Local hypersensitivity reactions (see section "Side effects") may resemble symptoms of the disease being treated.

Manifestations of hypercorticism (Cushing's syndrome) and reversible suppression of the hypothalamic-pituitary-adrenal (HPA) axis with adrenal gland function suppression in some individuals may result from increased systemic absorption of topical corticosteroids. If any of the above symptoms occur, the drug should be gradually discontinued by reducing the frequency of application or switching to a less potent corticosteroid. Abrupt discontinuation of treatment may lead to glucocorticoid insufficiency (see section "Side effects").

Risk factors for systemic effects include:

• Potency and formulation of the topical corticosteroid;
• Prolonged use;
• Application over a large skin surface area;
• Use on skin surfaces in contact (e.g., in areas prone to intertrigo or under occlusive dressings) — diapers in infants may act as occlusive dressings;
• Increased hydration of the stratum corneum;
• Application to areas with thin skin, such as the face;
• Application to damaged skin or under other conditions involving impaired skin barrier function.

Compared to adults, children and adolescents may absorb a proportionally greater amount of topical corticosteroid and are therefore more susceptible to systemic side effects. This is due to their underdeveloped skin barrier and larger skin surface area relative to body mass compared to adults.

Children

Long-term daily use of topical corticosteroids in children under 12 years of age should be avoided whenever possible, as they have a higher risk of developing adrenal suppression.

Psoriasis treatment

Topical corticosteroids should be used with caution in the treatment of psoriasis, as in some cases relapses, development of tolerance, risk of generalized pustular psoriasis, and symptoms of local or systemic toxicity due to impaired skin barrier function have been reported. When used for psoriasis treatment, patients should be under close medical supervision.

Application to the face

Prolonged application of the cream to facial skin is not recommended, as this area is more susceptible to atrophic changes.

Application to the eyelids

When applying the cream to the eyelids, care should be taken to avoid contact with the eyes, as repeated exposure may lead to cataract and glaucoma.

Visual disturbances

Visual disturbances may occur with both systemic and topical corticosteroid use. Patients reporting symptoms such as blurred vision or other visual disturbances should be referred to an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported following systemic and topical corticosteroid use.

Concomitant infections

Whenever treating infected inflammatory lesions, appropriate antibacterial agents should be prescribed. If infection spreads, topical corticosteroids should be discontinued and appropriate antibacterial therapy initiated.

Risk of infection with occlusive dressings

The risk of bacterial infections increases in warm and moist conditions, such as skin folds or under occlusive dressings. Therefore, the skin should be thoroughly cleaned each time before applying a new dressing.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat dermatitis occurring around chronic leg ulcers. However, such use is associated with an increased frequency of local hypersensitivity reactions and a higher risk of local infections.

Significant adrenal cortex suppression (morning plasma cortisol level below 5 µg/dL) is unlikely when the cream is used at therapeutic doses, unless more than 50% of the body surface is treated in adults or more than 20 g of the medicinal product is used per day.

Properties of excipients

The cream Arélia® contains imidazolidinyl urea, a metabolite of which is formaldehyde in trace amounts. Formaldehyde may cause allergic sensitization or skin irritation upon contact.

Arélia® cream contains cetostearyl alcohol, which may cause local skin reactions.

The medicinal product contains mineral oil. Patients should be warned not to smoke or be near open flames when applying the cream due to the risk of severe burns. If the medicinal product comes into contact with fabric (clothing, bed linen, dressings, etc.), the material may ignite easily and cause a serious fire. Washing clothing and bed linen reduces accumulation of the medicinal product in fabric but does not completely remove it.

Arélia® cream contains propylene glycol (100 mg per 1 g of the medicinal product), which may cause local skin irritation.

Topical steroid withdrawal syndrome

After prolonged use of topical corticosteroids, discontinuation of treatment may lead to recurrent disease (topical steroid withdrawal syndrome). Severe rebound flares may develop, presenting as dermatitis with marked redness, stinging, and burning, spreading beyond the originally treated area. The likelihood of such a reaction increases when treating more sensitive skin areas, such as the face or the inner surfaces of flexural joints. If the condition recurs within several days or weeks after successful completion of treatment, topical steroid withdrawal syndrome should be considered. Re-administration of the drug should be done with particular caution. Consultation with a specialist and consideration of alternative treatments are recommended.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of fluticasone propionate in pregnant women are limited.

Topical application of corticosteroids in pregnant animals may lead to fetal developmental abnormalities, although the relevance of these findings to pregnant women is not established. Therefore, fluticasone propionate should be prescribed to pregnant women only if the expected benefit to the mother outweighs the potential risk to the fetus and child. Use the lowest effective dose for the shortest possible duration.

Breastfeeding

The safety of topical corticosteroids in women during breastfeeding has not been established. It is unknown whether topical corticosteroid use may result in sufficient systemic absorption to lead to measurable levels of the drug in breast milk. In laboratory rat studies, fluticasone propionate was detected in breast milk following subcutaneous administration when a certain plasma level of the drug was achieved.

Fluticasone propionate cream should be prescribed during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the infant. If prescribed during breastfeeding, the cream should not be applied to the breasts to avoid accidental oral exposure of the infant.

Fertility

There are no data available to assess the effect of topical corticosteroids on human fertility.

Ability to affect reaction speed when driving or operating machinery

No specific studies have been conducted. Given the side effect profile, no effect on reaction speed during driving or operating machinery is expected.

Method of Administration and Dosage

Adults and children aged 3 months and older

The cream is particularly suitable for treating moist or weeping skin surfaces.

Apply the medicinal product as a thin layer to affected skin areas once or twice daily. With daily use, treatment duration should not exceed 4 weeks until improvement occurs; thereafter, reduce the frequency of cream application or switch to a less potent medicinal product. After applying the cream, allow sufficient time for absorption of the medicinal product before applying an emollient.

Once disease control is achieved, the frequency of topical corticosteroid use should be gradually reduced and eventually discontinued. Emollients should be used as maintenance therapy.

Sudden discontinuation of topical corticosteroids, especially potent ones, may result in symptom recurrence.

Treatment duration in adults and elderly patients

If there is no improvement or if the condition worsens within 2–4 weeks, the diagnosis and treatment should be re-evaluated.

Children aged 3 months and older

Children have a higher risk of local or systemic adverse reactions with topical corticosteroids; therefore, they are generally prescribed shorter treatment courses and less potent medicinal products compared to adults.

Use the cream in children with caution to ensure application of the minimum effective amount.

Treatment duration in children

If no improvement is observed after 7–14 days of treatment in children, therapy should be discontinued and further evaluation performed. If disease control is achieved within 7–14 days, continue using the minimum effective dose for the shortest possible duration. Daily treatment should not exceed 4 weeks.

Elderly patients

Clinical studies have not revealed differences in treatment response between elderly and younger patients. However, since elderly patients more frequently have impaired renal or hepatic function, which may lead to delayed elimination of the drug in case of systemic absorption, the minimum effective doses should be used for the shortest duration necessary to achieve the desired outcome.

Hepatic/Renal Impairment

In case of systemic absorption (e.g., when applied over large areas or for prolonged periods), metabolism and elimination of the medicinal product may be slowed, increasing the risk of systemic toxicity. Therefore, the minimum effective doses should be used for the shortest possible duration to achieve the desired therapeutic effect.

Children. Use for treatment of children aged 3 months and older.

Overdose

Symptoms

Fluticasone propionate may be absorbed in amounts sufficient to produce systemic effects when applied topically. Acute overdose is highly unlikely. Signs of hypercortisolism may occur in cases of chronic overdose or abuse (see section "Adverse Reactions").

Treatment

In case of overdose, cream application should be gradually discontinued by reducing the frequency of application or switching to a less potent topical corticosteroid, considering the risk of developing glucocorticosteroid insufficiency. Further treatment should be based on the patient's clinical condition.

Adverse Reactions

Adverse reactions are classified by system organ class and frequency of occurrence: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10,000, < 1/1000), very rare (< 1/10,000), including isolated cases, and not known (frequency cannot be estimated from available data).

Infections and infestations

Very rare: opportunistic infections.

Immune system disorders

Very rare: hypersensitivity.

Endocrine system disorders

Very rare: suppression of the hypothalamic-pituitary-adrenal (HPA) axis:

• weight gain / obesity;
• impaired weight gain / growth retardation in children;
• Cushingoid features (e.g., moon face, central obesity);
• decreased levels of endogenous cortisol;
• hyperglycemia/glucosuria;
• arterial hypertension;
• osteoporosis;
• cataract;
• glaucoma.

Skin and subcutaneous tissue disorders

Common: pruritus.

Uncommon: sensation of local burning of the skin.

Very rare: skin atrophy, thinning of the skin, striae, telangiectasia, pigment changes, hypertrichosis, allergic contact dermatitis, exacerbation of underlying symptoms, pustular psoriasis, erythema, rash, urticaria.

Not known: withdrawal syndrome — skin redness which may spread beyond the initially treated area, sensation of stinging or burning, pruritus, skin peeling, pustules with exudate (see section "Special precautions").

Eye disorders

Not known: blurred vision (see section "Special precautions").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is highly important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach and sight of children.

Packaging. 15 g or 30 g of cream in a tube, 1 tube per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Kievmedpreparat".

Manufacturer's name and address of the place of business

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.