Fluticasone

INSTRUCTIONS for medical use of the medicinal product FLUTICASONE

Composition:

Active substance: fluticasone;

1 g of the preparation contains fluticasone propionate 0.5 mg;

Excipients: mineral oil, propylene glycol, cetyl stearyl alcohol, isopropyl myristate, imidourea, anhydrous sodium hydrogen phosphate, anhydrous citric acid, polyethylene glycol cetyl stearyl ether, purified water.

Pharmaceutical form. Cream.

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

Pharmacotherapeutic group. Corticosteroids for dermatological use. Potent corticosteroids (group III). ATC code D07A C17.

Pharmacological properties.

Pharmacodynamics.

Fluticasone propionate is a glucocorticoid drug with high anti-inflammatory activity and a very low level of hypothalamic-pituitary-adrenal system suppression upon topical application, thus its therapeutic index is one of the widest among all currently available topical corticosteroids.

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

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

Pharmacokinetics.

Absorption.

After 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 application 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, consequently, elimination is rapid. Any drug entering systemic circulation through the skin is quickly inactivated. The primary metabolic pathway is hydrolysis to a carboxylic acid, which has very low glucocorticoid and anti-inflammatory activity.

Elimination.

Animal studies indicate that the route of elimination does not depend on the route of administration of fluticasone propionate. It is eliminated primarily in feces, and this process is completed within 48 hours.

Clinical characteristics.

Indications.

Adults.

Dermatoses responsive to corticosteroid therapy, such as:

• atopic dermatitis;
• nummular dermatitis (discoid eczema);
• lichen 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 rash and dermatitis.

Interaction with other medicinal products and other forms of interaction.

Concomitant use with agents that may inhibit CYP3A4 (such as ritonavir, itraconazole) inhibits corticosteroid metabolism, potentially leading to systemic effects. The clinical significance of such 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 who have previously experienced local hypersensitivity reactions to corticosteroids or any excipients. Local hypersensitivity reactions (see section "Side effects") may resemble the 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 patients 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 glucocorticosteroid insufficiency (see section "Side effects").

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 folds 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 side effects. This is due to children having an underdeveloped skin barrier and a larger skin surface area relative to body weight compared to adults.

Children.

Prolonged 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.

Treatment of psoriasis.

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 undesirable, 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 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 to evaluate 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.

When treating infected inflammatory lesions, appropriate antibacterial agents should always 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 those occurring in skin folds or under occlusive dressings; therefore, the skin should be thoroughly cleaned before each new dressing is applied.

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.

Pronounced suppression of adrenal cortex function (morning plasma cortisol level below 5 µg/dL) is unlikely with the use of fluticasone propionate cream at therapeutic doses, unless treating more than 50% of the body surface area in adults or using more than 20 g of the drug per day.

The medicinal product contains imidazolidinyl urea as an excipient, which metabolizes to formaldehyde in trace amounts. Formaldehyde may cause allergic sensitization or skin irritation upon contact.

The medicinal product contains cetyl stearyl alcohol as an excipient, which may cause local skin reactions (e.g., contact dermatitis).

The medicinal product contains propylene glycol as an excipient, which 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 cream, due to the risk of severe burns. If the product comes into contact with fabric (clothing, bed linens, dressings), the material may become highly flammable and pose a serious fire hazard. Washing clothing and bed linens reduces the 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 has been associated with fetal developmental abnormalities. A similar effect in pregnant women has not been established. However, fluticasone propionate should be prescribed during pregnancy 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 during breastfeeding has not been established. It is unknown whether topical corticosteroids may be systemically absorbed to such an extent that measurable amounts of the drug appear in breast milk. In laboratory rats, fluticasone propionate was detected in breast milk after subcutaneous administration when a certain plasma concentration was achieved.

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

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. Based on the side effect profile, no influence 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 the treatment of moist or weeping skin surfaces.

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

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

Relapse of the underlying condition may occur with abrupt discontinuation of topical corticosteroids, especially potent ones.

Treatment duration in adults, including elderly patients.

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

Children aged 3 months and older.

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

The medicinal product should be used with caution to ensure that the minimum effective amount of the medication is applied.

Treatment duration in children.

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

Elderly patients.

Clinical studies have not shown differences 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 the event of systemic absorption. Therefore, the minimum effective doses should be used for the shortest duration necessary to achieve the desired therapeutic effect.

Hepatic/Renal Impairment.

In the event of systemic absorption (e.g., with application over large areas or prolonged use), metabolism and elimination of the drug 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 outcome.

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 highly unlikely. With chronic overdose or misuse, signs of hypercortisolism may occur (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 glucocorticosteroid insufficiency. Further management should be based on the patient’s clinical condition.

Side effects

Side effects 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 (≥ 1/10000, < 1/1000), very rare (< 1/10000), including isolated cases, 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 weight gain/growth retardation in children;
• Cushingoid features (e.g. moon face, central obesity);
• decreased endogenous cortisol levels;
• hyperglycemia/glycosuria;
• arterial hypertension;
• osteoporosis;
• cataract;
• glaucoma.

Skin and subcutaneous tissue disorders

Common: pruritus.

Uncommon: sensation of local skin burning.

Very rare: skin atrophy, skin thinning, striae, telangiectasia, hypertrichosis, pigmentary changes, 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 and sight of children.

Packaging. 15 g in a tube in a carton.

Prescription status. Prescription only.

Manufacturer. Limited liability company "Pharmaceutical Company "Zdorovya".

Manufacturer's address and site of operations.

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

(all manufacturing stages, quality control, batch release)

100B, Shevchenka Street, Boryspil, Kyiv region, 08301, Ukraine (Building 4).

(all manufacturing stages, batch release)