Arelya

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

Composition:

active substance: fluticasone propionate;

1 g of ointment contains 0.05 mg fluticasone propionate;

excipients: propylene glycol, sorbitan sesquioleate, microcrystalline wax, mineral oil.

Pharmaceutical form. Ointment.

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

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

ATC code D07AC17.

Pharmacological Properties

Pharmacodynamics

Fluticasone propionate is a glucocorticoid medicinal product with high anti-inflammatory activity and a very low level of suppression of the hypothalamic-pituitary-adrenal system when applied topically, thus its therapeutic index is one of the widest among all currently available topical steroids.

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

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

Pharmacokinetics

Absorption

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

Distribution

Studies have shown that only a very small amount of orally administered fluticasone propionate reaches systemic circulation, and it 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, consequently, elimination is rapid. Any drug penetrating through 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 this process is completely finalized 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 generalized 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

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 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 to any of the excipients of this medicinal product. Local hypersensitivity reactions (see section "Adverse Reactions") 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 insufficiency in some individuals may result from increased systemic absorption of topical steroids. If any of the aforementioned symptoms occur, treatment with the medicinal product should be gradually discontinued by reducing the frequency of application or switching to a less potent corticosteroid. Abrupt cessation of treatment may lead to glucocorticoid insufficiency (see section "Adverse Reactions").

Risk factors for systemic effects include:

• Potency and formulation of the topical corticosteroid;
• Prolonged use;
• Application over large areas of skin;
• Use on skin surfaces in apposition, such as in areas of intertrigo or under occlusive dressings (in infants, diapers 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 proportionally greater amounts of topical corticosteroids and are therefore more susceptible to systemic adverse effects. This is due to children having an underdeveloped skin barrier and a larger skin surface area relative to body mass compared to adults.

Children

Prolonged daily use of topical corticosteroids in infants and children under 12 years of age should be avoided whenever possible, as they are at 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 ointment to facial skin is undesirable, as this area is more susceptible to atrophic changes.

Application to the eyelids

When applying the ointment 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 use of corticosteroids. Patients reporting symptoms such as blurred vision or other visual disturbances should be referred to an ophthalmologist for evaluation of 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 inflamed lesions that are infected, appropriate antimicrobial agents should be administered. If infection spreads, topical corticosteroids should be discontinued and appropriate antimicrobial 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 incidence of local hypersensitivity reactions and a higher risk of local infections.

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

Properties of excipients

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

Arеlia® ointment contains propylene glycol (50 mg per 1 g of the medicinal product), which may cause local skin reactions.

Topical steroid withdrawal syndrome

After prolonged use of topical corticosteroids, discontinuation of treatment may lead to the development of recurrent disease (topical steroid withdrawal syndrome). Severe rebound flares may occur, presenting as dermatitis with marked erythema, stinging, and burning, spreading beyond the originally treated area. The likelihood of such a reaction increases with treatment of more sensitive skin areas, such as the face or flexural areas. If the condition recurs within days or weeks after successful completion of treatment, this may indicate topical steroid withdrawal. Re-administration of the product should be done with particular caution. Consultation with a specialist is recommended, and alternative treatment options should be considered.

Use during pregnancy or breastfeeding

Pregnancy

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

Topical administration of corticosteroids in pregnant animals has been shown to cause 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. The lowest effective dose for the shortest possible duration should be used.

Breastfeeding

The safety of topical corticosteroids in women who are breastfeeding has not been established. It is unknown whether topical corticosteroids may be systemically absorbed to an extent that results in 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 concentration was achieved.

Fluticasone propionate ointment 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 ointment 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 adverse reaction profile, no effect on reaction speed when driving or operating machinery is expected.

Method of Administration and Dosage

Adults and children aged 3 months and older

The ointment is particularly suitable for the treatment of dry skin areas, as well as skin with lichenified or scaly lesions.

Apply the medicinal product as a thin layer to affected skin areas once or twice daily. The duration of treatment with daily application is up to 4 weeks until improvement occurs, after which the frequency of ointment application should be reduced or replaced with a less potent medicinal product. After applying the ointment, allow sufficient time for absorption of the medicinal product before applying an emollient.

After achieving disease control, the frequency of topical corticosteroid use should be gradually reduced until complete discontinuation, and emollients should be used for maintenance therapy.

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

Treatment duration in adults and elderly patients

If the condition worsens or no improvement is observed within 2–4 weeks, the diagnosis and treatment should be reassessed.

Children aged 3 months and older

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

The ointment should be used 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 ointment use in children, treatment should be discontinued and further evaluation performed. If disease control is achieved within 7–14 days, the minimum effective doses should be used for the shortest possible duration. The duration of daily treatment should not exceed 4 weeks.

Elderly patients

Clinical studies have not revealed differences in treatment response between elderly patients 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 treatment duration necessary to achieve the desired therapeutic effect.

Hepatic/Renal impairment

In case of systemic absorption (with application over large areas and prolonged use), metabolism and elimination of the drug may be slowed, increasing the risk of systemic toxicity. Therefore, to achieve the desired effect, the minimum effective doses should be used for the shortest possible duration.

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 unlikely. In cases of chronic overdose or misuse, signs of hypercorticism may occur (see section "Adverse Reactions").

Treatment

In case of overdose, ointment use 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.

Side effects

Adverse reactions are classified by organ systems 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 unknown (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;
• growth retardation / delayed weight gain 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 in the skin.

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

Unknown: withdrawal syndrome — skin redness that may spread beyond the initially treated area, sensation of stinging or burning, pruritus, skin desquamation, pustules with exudate (see section "Special precautions").

Eye disorders

Unknown: blurred vision (see section "Special precautions").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives are encouraged to report all 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 of children.

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

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's name and address of the place of business

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.