Fluticasone

INSTRUCTIONS for medical use of the medicinal product FLUTICASONE (FLUTICASONE)

Composition:

Active substance: fluticasone;

1 g of the preparation contains fluticasone propionate 0.05 mg;

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

Pharmaceutical form. Ointment.

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

Pharmacotherapeutic group. Corticosteroids for dermatological use. Potent corticosteroids (group III). ATC code D07AC17.

Pharmacological Properties.

Pharmacodynamics.

Fluticasone propionate is a glucocorticoid agent with high anti-inflammatory activity and very low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis following topical application, resulting in one of the widest therapeutic indices among currently available topical corticosteroids.

Fluticasone propionate exhibits high systemic activity after subcutaneous administration, but very low activity following oral administration, likely due to extensive first-pass metabolism. In vitro studies have demonstrated 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.

Following topical or oral administration, bioavailability is very low due to limited 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 ointment will be minimal.

Distribution.

Studies have shown that only a negligible 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, resulting in rapid elimination. 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 is independent of the route of administration. It is excreted primarily in feces, and elimination is complete within 48 hours.

Clinical characteristics.

Indications.

Adults.

Dermatoses sensitive to corticosteroid treatment, 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 of the excipients.

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 rash and other diaper dermatitis.

Interaction with other medicinal products and other forms of interaction.

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

Special precautions for use.

The drug should be used with caution in patients with a history of local hypersensitivity reactions to corticosteroids or any excipients. 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 gland dysfunction in some individuals may result from increased systemic absorption of topical corticosteroids. If any of the above symptoms occur, treatment 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 "Adverse reactions").

Risk factors for systemic effects include:

• Potency and formulation of the topical corticosteroid;
• Duration of treatment;
• Application over a large skin surface area;
• Use on skin surfaces in contact (e.g., in intertriginous areas) 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 a proportionally greater amount of topical corticosteroid 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 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 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 cataracts and glaucoma.

Visual disturbances.

Visual disturbances may occur with both systemic and topical use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist for evaluation of possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after 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.

Infection risk 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 before each new dressing application.

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 with therapeutic doses of the ointment unless more than 50% of the body surface is treated in adults or more than 20 g of the drug is used per day.

The presence of propylene glycol in the formulation may cause skin irritation.

The medicinal product 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 product comes into contact with fabric (clothing, bed linens, dressings, etc.), the material may ignite easily and cause a serious fire. Washing clothing and bed linens reduces accumulation of the product in fabric but does not completely remove it.

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 may cause fetal developmental abnormalities, although the relevance of these findings to pregnant women is not established. However, 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 should be used for the shortest possible duration.

Breastfeeding.

The safety of topical corticosteroids during breastfeeding has not been established. It is unknown whether topical corticosteroids may lead to systemic absorption sufficient to result in measurable levels of the drug in breast milk. In animal studies, fluticasone propionate was detected in breast milk after subcutaneous administration that achieved certain plasma levels.

Fluticasone propionate ointment should be prescribed during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the infant. If treatment is necessary 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 studies have been conducted on this effect. Given the adverse reaction profile, no effect on reaction speed during driving or operating machinery is expected.

Dosage and Administration

Adults and children aged 3 months and older

Ointment is most suitable for treating dry areas of skin, as well as skin with lichenified or scaly lesions.

Apply a thin layer of the medication to affected skin areas once or twice daily. With daily use, treatment duration should not exceed 4 weeks until improvement occurs; thereafter, the frequency of ointment application should be reduced or treatment should be switched to a less potent agent. After applying the ointment, allow sufficient time for drug absorption before applying an emollient.

Once disease control is achieved, the frequency of topical corticosteroid use should be gradually reduced until complete discontinuation, with emollients used for maintenance therapy.

Relapse of existing disease symptoms may occur following abrupt discontinuation of topical corticosteroids, especially potent ones.

Treatment duration in adults and elderly patients

If the condition worsens or fails to improve within 2–4 weeks, the diagnosis and treatment regimen should be re-evaluated.

Children aged 3 months and older

Children are at higher risk of developing local or systemic adverse reactions with topical corticosteroids; therefore, they are generally treated with shorter treatment courses and less potent agents compared to adults.

The medicinal product should be used 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 the child should be further evaluated. If disease control is achieved within 7–14 days, the minimum effective dose should be maintained for the shortest possible duration. Daily treatment should not exceed 4 weeks.

Elderly patients

Clinical studies have not revealed any difference in treatment response between elderly and younger patients. However, elderly patients are more likely to have impaired renal or hepatic function, which may lead to delayed elimination of the drug in case of systemic absorption. Therefore, the minimum effective dose should be used for the shortest duration sufficient to achieve the desired therapeutic outcome.

Hepatic/renal impairment

In case of systemic absorption (e.g., when applied over large surface areas for prolonged periods), metabolism and elimination of the drug may be slowed, increasing the risk of systemic toxicity. Therefore, the minimum effective dose should be used for the shortest possible duration required 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 sufficient amounts during topical application to produce systemic effects. Acute overdose is unlikely. With chronic overdose or misuse, signs of hypercortisolism may occur (see section "Adverse Reactions").

Treatment

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

Side effects

Side effects 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 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;
• delayed increase in body weight/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: local sensation of skin burning.

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

Eye disorders

Not known: visual blurring (see section "Special precautions").

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Do not freeze. Keep out of reach of children.

Packaging. 15 g in a tube in a carton.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and location of its business activities.

Ukraine, 61013, Kharkiv region, Kharkiv city, Shevchenka Street, building 22.

(all stages of manufacturing, quality control, batch release)

Ukraine, 08301, Kyiv region, Boryspil city, Shevchenka Street, building 100, letter B-II (corpus 4).

(all stages of manufacturing, batch release)