Cutivate^® (Ointment, Cream) Instructions for Use

ATC Code

D07AC17 (Fluticasone)

Active Substance

Fluticasone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Topical corticosteroids for external use

Pharmacotherapeutic Group

Topical glucocorticosteroid

Pharmacological Action

Glucocorticosteroid for external use. It has anti-inflammatory, antipruritic, and vasoconstrictive properties.

The anti-inflammatory properties are due to numerous mechanisms of inhibiting the late phase of allergic reactions, including a reduction in the number of mast cells, attenuation of chemotaxis and activation of eosinophils, decreased production of cytokines by lymphocytes, monocytes, mast cells, and eosinophils, as well as inhibition of arachidonic acid metabolism.

Fluticasone is a glucocorticosteroid with a pronounced local anti-inflammatory effect. When applied to the skin, the likelihood of suppression of the hypothalamic-pituitary-adrenal system (HPA) function is insignificant. In vitro studies have shown that Fluticasone is characterized by high selectivity and affinity for glucocorticoid receptors. According to clinical studies, when entering the systemic circulation, Fluticasone is rapidly transformed in the liver into an inactive metabolite (carboxylic acid) with subsequent rapid elimination from the body. Due to these properties, the drug Cutivate^® has a high therapeutic index.

Fluticasone does not cause unforeseen hormonal disorders and does not have a significant effect on the central and peripheral nervous systems, gastrointestinal tract, cardiovascular and respiratory systems.

Pharmacokinetics

Absorption

Due to limited absorption of fluticasone through the skin, the bioavailability of the drug with external use is very low. The bioavailability of fluticasone when taken orally is close to zero due to very low absorption from the gastrointestinal tract and extensive metabolism during the first pass through the liver, which ensures a low level of systemic exposure in case of accidental ingestion of the drug.

Distribution

After entering the systemic circulation, Fluticasone quickly enters the bile and is excreted through the intestines. Fluticasone does not accumulate in tissues and does not bind to melanin.

Metabolism

According to the results of preclinical and clinical studies, Fluticasone has a high metabolic clearance with subsequent rapid elimination from the body. Thus, the drug that enters the systemic circulation through the skin is rapidly inactivated. The main metabolic pathway is hydrolysis to carboxylic acid; this metabolite has very weak glucocorticoid and anti-inflammatory activity.

Excretion

Fluticasone is excreted within 48 hours mainly through the intestines.

Indications

For adults and children aged 1 year and older to relieve inflammation and itching in acute and chronic dermatoses sensitive to glucocorticosteroid therapy, such as

• Atopic dermatitis (including atopic dermatitis in children aged 1 year and older);
• Nummular dermatitis (discoid eczema);
• Seborrheic dermatitis;
• Psoriasis (except for widespread plaque psoriasis);
• Lichen simplex chronicus;
• Lichen planus;
• Contact or allergic contact dermatitis;
• Erythroderma (as an adjunct to systemic glucocorticosteroid therapy);
• Inflammatory reactions to insect bites.

The drug Cutivate^® is used to reduce the risk of relapse in the chronic form of atopic dermatitis, if a therapeutic effect was observed during the treatment of the acute phase of the disease.

ICD codes

Dosage Regimen

Cream

For external use.

The drug is prescribed to adults, elderly patients, children aged 1 year and older.

The total course of therapy is 4 weeks.

The use of the cream is especially indicated for treating moist or weeping affected surfaces.

Treatment of acute and chronic dermatoses

Cutivate^® cream should be applied 1 or 2 times/day in a thin layer in an amount no greater than necessary to cover the entire affected area and gently rubbed in. The duration of treatment is up to 4 weeks until the effect is achieved, after which the frequency of application should be reduced or switched to treatment with a less active drug. It is necessary to allow sufficient time for the Cutivate^® drug to be absorbed before applying an emollient. If the condition worsens or does not improve within 2 weeks, the treatment and diagnosis should be re-evaluated.

When treating atopic dermatitis, topical glucocorticosteroid therapy should be discontinued gradually against the background of maintenance therapy with an emollient after disease control is achieved.

Resumption of the original symptoms of the dermatosis may occur with abrupt discontinuation of topical glucocorticosteroid therapy, especially when using highly active drugs.

Reducing the risk of atopic dermatitis relapse

After achieving a therapeutic effect in the acute phase of the disease, the frequency of cream application is reduced: it is recommended to apply the drug once, 2 times a week without an occlusive dressing.

The drug Cutivate^® is applied to all previously affected areas of the skin or to areas where a relapse of the disease can be expected. This dosage regimen should be combined with the daily use of emollients. Regular monitoring of the patient’s condition is necessary.

Special patient groups

Children aged 1 year and older

Children have a higher likelihood of developing local and systemic side effects from the use of topical glucocorticosteroids, and, in general, children are recommended shorter courses of treatment and the prescription of less active drugs compared to adults. The course of therapy for children should not exceed 4 weeks.

Caution should be exercised when using Cutivate^® cream, ensuring the application of the drug in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Elderly patients

Clinical studies have not revealed differences in outcomes between groups of elderly patients and younger patients. The higher prevalence of reduced liver or kidney function in elderly patients may lead to a slowdown in the elimination of the active substance from the body in case of its systemic absorption. Thus, Cutivate^® cream should be applied in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Patients with impaired renal and/or hepatic function

In case of systemic absorption (with prolonged application of the cream to a large area), the metabolism and excretion of the active substance are slowed down in patients with impaired renal and/or hepatic function, which increases the risk of systemic toxicity. Thus, the cream should be applied in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Ointment

For external use.

The drug is prescribed to adults, elderly patients, children aged 6 months and older.

The total course of therapy is 4 weeks.

The use of the ointment is especially indicated for treating dry, lichenified or scaly lesions.

Treatment of acute and chronic dermatoses

Cutivate^® ointment should be applied 1 or 2 times/day in a thin layer in an amount no greater than necessary to cover the entire affected area and gently rubbed in. The duration of treatment is up to 4 weeks until the effect is achieved, after which the frequency of application should be reduced or switched to treatment with a less active drug. It is necessary to allow sufficient time for the Cutivate^® ointment to be absorbed before applying an emollient. If the condition worsens or does not improve within 2 weeks, the treatment and diagnosis should be re-evaluated.

When treating atopic dermatitis, topical glucocorticosteroid therapy should be discontinued gradually against the background of maintenance therapy with an emollient after disease control is achieved.

Resumption of the original symptoms of the dermatosis may occur with abrupt discontinuation of topical glucocorticosteroid therapy, especially when using highly active drugs.

Reducing the risk of atopic dermatitis relapse

After achieving a therapeutic effect in the acute phase of the disease, the frequency of ointment application is reduced: it is recommended to apply the drug once, 2 times a week without an occlusive dressing.

The drug Cutivate^® is applied to all previously affected areas of the skin or to areas where a relapse of the disease can be expected. This dosage regimen should be combined with the daily use of emollients. Regular monitoring of the patient’s condition is necessary.

Special patient groups

Children aged 6 months and older

Children have a higher likelihood of developing local and systemic side effects from the use of topical glucocorticosteroids, and, in general, children are recommended shorter courses of treatment and the prescription of less active drugs compared to adults. The course of therapy for children should not exceed 4 weeks.

Caution should be exercised when using Cutivate^® ointment, ensuring the application of the drug in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Elderly patients

Clinical studies have not revealed differences in outcomes between groups of elderly patients and younger patients. The higher prevalence of reduced liver or kidney function in elderly patients may lead to a slowdown in the elimination of the active substance from the body in case of its systemic absorption. Thus, Cutivate^® ointment should be applied in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Patients with impaired renal and/or hepatic function

In case of systemic absorption (with prolonged application of the cream to a large area), the metabolism and excretion of the active substance are slowed down in patients with impaired renal and/or hepatic function, which increases the risk of systemic toxicity. Thus, the ointment should be applied in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Adverse Reactions

The adverse reactions presented below are listed according to the affected organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very rare (<1/10,000, including isolated cases). Frequency categories were formed based on post-marketing surveillance.

Infections and infestations very rare – opportunistic infections.

Immune system disorders very rare – hypersensitivity (itching at the application site, rash, swelling).

Endocrine disorders very rare – HPA axis suppression (weight gain or obesity, slow weight gain or growth retardation in children, cushingoid features (e.g., moon face, central obesity), decreased endogenous cortisol concentration, hyperglycemia or glucosuria, arterial hypertension, osteoporosis, cataract, glaucoma.

Skin and subcutaneous tissue disorders common – itching at the application site of the cream; uncommon – burning at the application site of the cream; very rare – skin thinning, atrophy, striae, telangiectasia, hypopigmentation, hypertrichosis, allergic contact dermatitis, exacerbation of symptoms of the underlying disease, pustular psoriasis, erythema, rash, urticaria.

Any of the adverse reactions listed above should be reported to a doctor. The decision on further treatment strategy should be made by the doctor.

If any of the adverse reactions mentioned in the instructions worsen or any other adverse reactions not mentioned in the instructions are noted, the patient should inform the doctor.

Contraindications

• Hypersensitivity to the active substance or any other component of the drug;
• Primary skin lesions of bacterial, viral and fungal etiology;
• Rosacea;
• Acne vulgaris;
• Perioral dermatitis;
• Perianal and genital pruritus;
• Pruritus without symptoms of inflammation;
• Children under 1 year of age.

With caution the drug should be used for psoriasis, renal failure, hepatic failure, elderly patients, in children (from 1 year to 12 years).

Use in Pregnancy and Lactation

Fertility

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

Pregnancy

There is a limited amount of data on the use of fluticasone during pregnancy.

Preclinical studies have revealed that topical application of corticosteroids in pregnant animals can cause abnormalities in embryonic development, but the significance of this phenomenon for humans has not been established.

The drug Cutivate^® can be prescribed only if the intended benefit to the mother outweighs any possible risk to the fetus. In this case, the cream should be applied in the minimum amount for the shortest period of time sufficient to achieve a clinical effect.

Breastfeeding period

The safety of topical glucocorticosteroid therapy has not been established.

There are no available data to confirm the possibility of systemic absorption of topical glucocorticosteroids in an amount sufficient for their detection in breast milk.

Preclinical studies have revealed that during breastfeeding, with subcutaneous administration in amounts sufficient for detection in plasma, Fluticasone was detected in milk.

The drug Cutivate^® can be prescribed during breastfeeding only if the intended benefit to the mother outweighs any possible risk to the child.

When using the drug Cutivate^® during breastfeeding, the drug should not be applied to the breast area to prevent its accidental ingestion by the child.

Use in Hepatic Impairment

With caution the drug should be used in hepatic failure.

Use in Renal Impairment

With caution the drug should be used in renal failure.

Pediatric Use

Contraindicated in children under 1 year of age.

With caution the drug should be used in children (from 1 year to 12 years).

Geriatric Use

With caution the drug should be used in elderly patients.

Special Precautions

The drug Cutivate^® should be used with caution in patients with a history of developing local hypersensitivity reactions to other glucocorticosteroids. Local hypersensitivity reactions may resemble the symptoms of the underlying disease.

Manifestations of hypercortisolism (Cushing’s syndrome) and reversible inhibition of the HPA axis, leading to glucocorticoid deficiency, in some cases occur due to increased systemic absorption of topical glucocorticosteroids. In such cases, it is necessary to gradually discontinue treatment by reducing the frequency of applications or replace the drug Cutivate^® with a less active glucocorticosteroid. Abrupt discontinuation of treatment may lead to glucocorticoid deficiency.

Risk factors for the development of pronounced systemic reactions include the following

• Potency and dosage form of the topical glucocorticosteroid;
• Duration of treatment;
• Application to large areas of the skin;
• Application to occluded areas of the skin, for example, to intertriginous areas or under occlusive dressings (in children, a diaper can act as an occlusive dressing);
• Increased hydration of the stratum corneum of the dermis;
• Application to areas with thin skin, such as the face;
• Damaged skin or other conditions potentially accompanied by damage to the skin barrier;
• Compared to adults, children are likely to absorb more topical glucocorticosteroid, thus increasing the risk of systemic adverse reactions. This is due to the immaturity of the skin barrier and a higher ratio of body surface area to body weight in children compared to adults.

In children aged from 1 year to 12 years, long-term continuous therapy with topical corticosteroids should be avoided whenever possible, as there is a possibility of adrenal function suppression.

Caution should be exercised when prescribing topical corticosteroids for the treatment of psoriasis, as there are reports of early relapses, development of tolerance, risk of generalized pustular psoriasis, and local or systemic toxicity due to impaired skin barrier function. Use in psoriasis requires careful monitoring of the patient’s disease course.

Long-term application of Cutivate^® cream to the facial area is undesirable, as the skin in this area is more susceptible to atrophic changes.

When applying Cutivate^® cream to the eyelids, care must be taken to ensure that the preparation does not get into the eyes, since repeated contact of the preparation with the ocular mucosa can lead to the development of cataract and glaucoma.

In case of secondary infection of skin lesions, appropriate antibacterial therapy should be prescribed. If signs of infection spreading appear, topical corticosteroids should be discontinued and appropriate antibacterial therapy should be prescribed.

Bacterial infections develop more easily in warm and moist conditions in natural skin folds or under occlusive dressings; therefore, the skin should be thoroughly cleansed each time before applying a new dressing.

Topical corticosteroid therapy is sometimes used to treat dermatitis developing around chronic ulcers of the lower limbs. However, this may be associated with a higher incidence of local hypersensitivity reactions and infectious complications.

Significant suppression of the HPA axis function (morning plasma cortisol level less than 5 mcg/dL) in adults is unlikely when using Cutivate^® in the recommended doses, except in cases of application to more than 50% of the body surface area and in amounts exceeding 20 g/day.

The preparation Cutivate^® contains imidurea as an excipient, which is metabolized to form trace amounts of formaldehyde. Formaldehyde may cause allergic reactions or irritation upon contact with the skin.

Effect on ability to drive vehicles and operate machinery

No studies have been conducted to assess the effect of Cutivate^® on the ability to drive vehicles or operate machinery. Based on the adverse reaction profile of Cutivate^®, no adverse effect on driving vehicles and operating machinery is anticipated.

Overdose

Symptoms with topical use, Fluticasone can be absorbed in sufficient amounts to produce systemic effects. The likelihood of acute overdose is extremely low; however, with chronic overdose or improper use of Cutivate^®, signs of hypercortisolism (Cushing’s syndrome) may develop.

Treatment in case of fluticasone overdose, the preparation should be withdrawn gradually – by reducing the frequency of its application or switching to a less potent corticosteroid to avoid the risk of glucocorticoid insufficiency. If a clinical picture of drug overdose develops, symptomatic therapy is indicated.

Drug Interactions

Concomitant therapy with medicinal products that have an inhibitory effect on the CYP3A4 isoenzyme (e.g., ritonavir, itraconazole) may lead to inhibition of corticosteroid metabolism, which is accompanied by increased systemic exposure. The degree of clinical significance of such an interaction depends on the activity of the CYP3A4 isoenzyme inhibitor, the dose and route of administration of the corticosteroid; however, such an interaction is unlikely with the topical route of administration.

Storage Conditions

The preparation should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 2 years.

Dispensing Status

The preparation is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.