Kutivait

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KUTIVEYT (CUTIVATE)

Composition:

Active substance: fluticasone propionate;

1 g of ointment contains 50 mcg of fluticasone propionate;

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

Pharmaceutical form. Ointment.

Main physicochemical characteristics: homogeneous, semi-transparent ointment 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 agent with high anti-inflammatory activity and very low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis upon 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 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.

Following topical or oral administration, bioavailability is very low due to limited absorption through the skin or gastrointestinal tract and extensive first-pass metabolism. Oral bioavailability approaches zero; therefore, systemic effects of fluticasone propionate after any internal use of the ointment are expected to 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 and 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 is independent of the administration route of fluticasone propionate. It is excreted predominantly 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);
• chronic simplex lichen (neurodermatitis), lichen planus;
• seborrheic dermatitis;
• irritant or allergic contact dermatitis;
• discoid lupus erythematosus;
• generalized erythroderma (as an adjunctive therapy);
• 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.

Acne vulgaris.

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 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 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 of the excipients. Local hypersensitivity reactions (see section "Side effects") may mimic 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 suppression in some individuals may result from increased systemic absorption of topical steroids. If any of the above symptoms occur, treatment with 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;
• Duration of treatment;
• Application over a large surface area of skin;
• Use on skin surfaces in close contact (e.g., in 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 areas of 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 their underdeveloped skin barrier and 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, the patient 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. 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, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported following systemic and topical corticosteroid use.

Concomitant infections.

Whenever treating inflamed, infected 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, moist environments, such as 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 frequency 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 Cutivate ointment when used at therapeutic doses, unless more than 50% of the body surface is treated in adults or more than 20 g of the drug is used per day.

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

Cutivate ointment contains propylene glycol (50 mg per 1 g of product) as an excipient, which may cause local skin reactions.

Topical steroid withdrawal syndrome.

After prolonged use of topical corticosteroids, discontinuation of treatment may lead to recurrent flare-ups (topical steroid withdrawal syndrome). Severe recurrent flares may develop, presenting as dermatitis with marked redness, stinging, and burning, spreading beyond the initially 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, this may indicate topical steroid withdrawal. Re-treatment with the drug should be done with particular caution. Consultation with a specialist is recommended, and consideration should be given to alternative treatments.

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 has been shown to 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 be systemically absorbed to an extent that measurable amounts of the drug appear in breast milk. In laboratory rat studies, fluticasone propionate was detected in breast milk after subcutaneous administration, once 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 to the ointment.

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 on this effect have been conducted. Given 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 ointment is particularly suitable for the treatment of dry areas of skin, as well as skin with eczematous or scaly lesions.

Apply the medication 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 treatment should be switched to a less potent agent. After applying the ointment, allow sufficient time for drug absorption before applying an emollient.

After achieving disease control, the frequency of topical corticosteroid use should be gradually reduced until complete discontinuation, while continuing emollients as maintenance therapy.

Recurrence of existing disease symptoms may occur with abrupt discontinuation of topical corticosteroids, especially potent ones.

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 re-evaluated.

Children aged 3 months and older

Children have a higher likelihood of developing local or systemic adverse reactions with topical corticosteroids; therefore, they are generally prescribed shorter treatment courses and less potent agents than adults.

Cutivate ointment should be used with caution to ensure the minimum effective amount of the drug is applied.

Treatment duration in children

If no improvement is observed after 7–14 days of treatment with the ointment in children, treatment should be discontinued and the child should undergo further evaluation. If disease control is achieved within 7–14 days of treatment, the minimum effective dose should be continued for the shortest possible duration. The duration of 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 case of systemic absorption. Therefore, the minimum effective dose should be used for the shortest duration necessary to achieve the desired therapeutic effect.

Hepatic/Renal Insufficiency

In case of systemic absorption (with application over large areas or 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. Indicated 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. With chronic overdose or abuse, signs of hypercortisolism may occur (see section "Adverse Reactions").

Treatment

In case of overdose, ointment application should be gradually discontinued by reducing the frequency of application or switching to a less potent topical corticosteroid, considering the risk of developing glucocorticoid insufficiency. Further management 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 (>1/1,000, <1/100), rare (>1/10,000, <1/1,000), 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;
• weight gain delay/growth retardation in children;
• Cushingoid signs (e.g. moon face, central obesity);
• decreased levels of endogenous cortisol;
• hyperglycemia/glycosuria;
• arterial hypertension;
• osteoporosis;
• cataract;
• glaucoma.

Skin and subcutaneous tissue disorders

Common: pruritus.

Uncommon: sensation of local skin burning.

Very rare: skin thinning, skin atrophy, striae, telangiectasia, pigmentary 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 prickling or burning, pruritus, skin desquamation, pustules with exudative content (see section "Special precautions for use").

Eye disorders

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

Shelf life. 2 years.

Storage conditions. Store below 30 °C. Keep out of reach of children.

Packaging. 15 g of ointment in an aluminum tube with protective membrane and polypropylene cap, packed in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Delpharm Poznan S.A., Poland / Delpharm Poznan S.A., Poland.

Manufacturer's address and place of business.

189, Grunwaldzka Str., 60-322 Poznan, Poland /
189 Grunwaldzka Str., 60-322 Poznan, Poland.