FeniVate ointment for external use 0.005%, 15g

Composition

• Active ingredient: Fluticasone propionate (micronized) – 0.05 mg;
• Auxiliary substances:  
• Propylene Glycol – 50.00 mg.
• Sorbitan sesquioleate – 5.00 mg;
• Microcrystalline wax – 250.00 mg;
• Liquid paraffin – up to 1.00 g.

Pharmacological action

Due to the limited absorption of fluticasone through the skin, the bioavailability of the drug with external use is very low. The oral bioavailability of fluticasone is close to zero due to the very low level of absorption in 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. The degree of binding to plasma proteins is quite high (91%). Fluticasone does not accumulate in the tissues and does not bind to melanin.

Metabolism

According to the results of preclinical and clinical studies, fluticasone has a high metabolic clearance followed by rapid elimination from the body. Thus, the drug that enters the systemic circulation through the skin is quickly inactivated. The main route of metabolism is hydrolysis to carboxylic acid; this metabolite has very weak glucocorticosteroid and anti-inflammatory activity.

Deduction

The rate of elimination of intravenously administered fluticasone propionate is linear in the dose range from 250 to 1000 micrograms and is characterized by high plasma clearance (CL=1.1 l / min).

The maximum plasma concentration decreases by approximately 98% over 3-4 hours, and only low plasma concentrations were associated with a final elimination half-life of 7.8 hours. Renal clearance of fluticasone propionate is insignificant (

Pharmacodynamics

Mechanism of action

Glucocorticosteroids for external use have anti-inflammatory properties. Anti-inflammatory properties are due to numerous mechanisms of inhibition of late-phase allergic reactions, including a decrease in the number of mast cells, a decrease in chemotaxis and activation of eosinophils, a decrease in cytokine production by lymphocytes, monocytes, mast cells and eosinophils, as well as inhibition of arachidonic acid metabolism.

Fluticasone belongs to glucocorticosteroids (corticosteroids) with a pronounced local anti-inflammatory effect. Fluticasone propionate is highly lipophilic, which allows it to penetrate the double lipid layer of the target cell and bind to glucocorticoid receptors in the cytoplasm.

In vitro studies have shown that fluticasone is characterized by high selectivity and affinity for glucocorticosteroid receptors.

The Fluticasone propionate-receptor complex stimulates or suppresses mRNA transcription and subsequent protein synthesis. The production of enzymes responsible for anti-inflammatory action increases, while the production of inflammatory mediators decreases.

The production of enzymes responsible for anti-inflammatory action increases, while the production of inflammatory mediators decreases. When applied to the skin, the probability of inhibition of the function of the hypothalamic-pituitary-adrenal system (HPA) is insignificant.

According to clinical studies, when fluticasone enters the systemic circulation, it is rapidly transformed in the liver to an inactive metabolite (17b-carboxylic acid), followed by rapid elimination from the body. Due to these properties, FeniVeyt has a high therapeutic index.

Pharmacodynamic effects

Fluticasone does not cause unexpected hormonal disorders, does not significantly affect the central and peripheral nervous systems, gastrointestinal tract, cardiovascular and respiratory systems.

Indications

FeniVate, which contains the effective glucocorticosteroid fluticasone, is used in adults and children aged 10 years and older to relieve symptoms associated with atopic dermatitis (eczema), seborrheic dermatitis, accompanied by irritation or allergic contact dermatitis.

Use during pregnancy and lactation

Fertility

There are no available data to assess the effect of corticosteroids for external use on human fertility. In animal studies, no effect of fluticasone propionate on fertility was found.

Pregnancy

There is limited data on the use of fluticasone during pregnancy. In studies of reproductive function in animals, undesirable effects characteristic of strong corticosteroids were observed only at a high level of systemic exposure.

As a result of preclinical studies, it was found that external use of corticosteroids in pregnant animals can cause fetal development abnormalities, however, the significance of this phenomenon for humans has not been established.

The use of the drug during pregnancy is not recommended, except in cases where the benefit to the mother exceeds the potential risk to the fetus and only under the supervision of a doctor. Before using during pregnancy, you should consult your doctor. In this case, the ointment should be applied in a minimum amount for the shortest possible period of time, sufficient for the manifestation of a clinical effect.

Breast-feeding period

The safety of corticosteroid therapy for external use during breastfeeding has not been established.

There are no available data to support the possibility of systemic absorption of corticosteroids for external use in a volume sufficient for their detection in breast milk.

As a result of preclinical studies, it was found that during breastfeeding, when administered subcutaneously in quantities sufficient for determination in plasma, fluticasone was detected in milk.

The use of the drug during breastfeeding is not recommended, except in cases where the intended benefit to the mother exceeds any possible risks to the child. Before using during breastfeeding, you should consult your doctor.

When using the drug during breastfeeding, the drug should not be applied to the area of the mammary glands to prevent its accidental ingestion by the child.

Contraindications

• Hypersensitivity to the Active ingredient or any other component that is part of the drug;
• Skin infections without prescribed therapy;
• Primary skin lesions of bacterial, viral and fungal etiology;
• Rosacea;
• Common acne;
• Perioral dermatitis;
• Perianal and genital pruritus;
• Pruritus without symptoms of inflammation;
• Children under 10 years of age.

Do not apply to closed areas of the skin (for example, on diaper rash or under occlusive dressings).

With caution:

Kidney failure, liver failure, elderly age, children’s age (from 10 to 12 years).

Side effects

The adverse reactions listed below are listed according to the lesion of organs and organ systems and frequency of occurrence. The frequency of occurrence is determined as follows: very common (≥ 1/10), common (≥ 1/100) and

the frequency of occurrence of adverse reactions

Infectious and parasitic diseases: Very rarely – Opportunistic infections.

Immune system disorders: Very rare-Hypersensitivity*: itching at the application site, rash, swelling.

Endocrine system disorders (HPA inhibition): Very rarely-Weight gain or obesity; Slow weight gain or stunted growth in children; Kushingoid features (for example, moon-shaped face, central obesity); Decreased endogenous cortisol concentration; Hyperglycemia or glucosuria; Arterial hypertension; Osteoporosis; Cataracts; Glaucoma.

Disorders of the skin and subcutaneous tissues

Often – Itching at the site of application of the ointment.

Infrequently-Burning sensation at the application site.

Very rarely – Thinning of the skin, atrophy, striae, telangiectasia, pigmentation changes, hypertrichosis, allergic contact dermatitis, exacerbation of symptoms of the underlying disease, pustular psoriasis, erythema, rash, urticaria.

* Local hypersensitivity reactions may resemble the symptoms of the disease for which this therapy is used.

You should inform your doctor if you experience any of the adverse reactions listed above. The decision on the future treatment strategy should be made by the doctor.

If any of the adverse reactions listed in the instructions get worse, or you notice any other adverse reactions not listed in the instructions, tell your doctor.

Interaction

Concomitant therapy with drugs that have an inhibitory effect on the CYP3A4 isoenzyme (for example, ritonavir, itraconazole) may lead to inhibition of corticosteroid metabolism, which is accompanied by increased systemic exposure. The degree of clinical significance of such interactions depends on the activity of the inhibitor of the CYP3A4 isoenzyme, the dose and method of administration of corticosteroids, but such an interaction is unlikely with the external method of application.

How to take it, course of administration and dosage

Externally.

It is indicated for adults, the elderly, and children 10 years and older.

The use of the ointment is especially indicated for the treatment of dry, lichenized or flaky foci.

Apply FeniVeyt ointment 1 or 2 times a day in a thin layer in an amount not greater than necessary to cover the entire affected area, and gently rub rub 1 or 2 times a day until the effect is achieved, but not more than 4 weeks.

It is necessary to maintain sufficient time for absorption of FeniVeyt ointment before applying the emollient.

If the condition worsens or does not improve within 2 weeks, the treatment and diagnosis should be re-evaluated.

When using fluticasone propionate, care should be taken to ensure that the application of the minimum amount that has a therapeutic effect. Resumption of the initial symptoms of dermatosis may occur when corticosteroid therapy for external use is discontinued, especially in the case of highly active drugs.

Special patient groups

Children 10 years and older

Do not use in children under 10 years of age. Children are more likely to develop local and systemic side effects when using external corticosteroids, and, in general, children are recommended to take shorter courses of treatment and prescribe less active medications compared to adults.

Caution should be exercised when applying FeniVeyt ointment, ensuring that the drug is applied in the minimum amount for the shortest possible period of time, sufficient for the manifestation of a clinical effect.

Elderly patients

In clinical trials, there were no differences in results between groups of elderly patients and younger patients.

The high prevalence of reduced hepatic or renal function in elderly patients may lead to a delay in the elimination of the Active ingredient from the body in the event of its systemic absorption.

Thus, FeniVeyt ointment should be applied in a minimum amount for the shortest possible period of time, sufficient for the manifestation of a clinical effect.

Patients with impaired renal and/or hepatic function

In the case of systemic absorption (with prolonged application of the ointment to a large area), the metabolism and excretion of the Active ingredient slows down in patients with impaired renal and/or liver function, which increases the risk of systemic toxicity. Thus, it is necessary to apply the ointment in a minimum amount for the shortest possible period of time, sufficient for the manifestation of a therapeutic effect.

Overdose

Symptoms

When applied externally, fluticasone can be absorbed in sufficient quantities to manifest a systemic effect. The probability of an acute overdose is extremely low, but with a chronic overdose or improper use of the drug FeniVeyt, signs of hypercorticism (Itsenko-Cushing syndrome) may develop.

Treatment

In case of fluticasone overdose, discontinuation of the drug is carried out gradually – by reducing the frequency of its application or switching to less active corticosteroids in order to avoid the risk of developing glucocorticoid insufficiency. If the clinical picture of drug overdose develops, symptomatic therapy is indicated.

Special instructions

Manifestations of hypercorticism (Itsenko-Cushing syndrome) and reversible HPA inhibition, leading to glucocorticoid insufficiency, in some cases occur due to increased systemic absorption of corticosteroids for external use.

In such cases, it is necessary to gradually stop treatment, reducing the frequency of applications, or replace the drug FeniVeyt with a less active corticosteroid. Sudden discontinuation of treatment may result in glucocorticoid insufficiency.

Risk factors for severe systemic reactions include the following::

• activity and GCS dosage form for external application;
• duration of treatment;
• the application of large areas of the skin;
• increased hydration of the Horny layer of the dermis;
• drawing on the area with thin skin such as the face;
• the damaged skin or other conditions, potentially accompanied by damage to the skin barrier;
• in comparison with older children, there is a probability of absorption of a larger number of GCS for external use, 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 from 10 to 12 years of age, long-term continuous therapy with corticosteroids for external use should be avoided if possible, since there is a possibility of suppression of adrenal function.

Cases of visual impairment have been reported with systemic and topical corticosteroids, resulting from increased systemic availability and direct eye contact.

Therefore, if a patient has symptoms such as blurred vision or other visual impairments, consideration should be given to referring the patient for consultation with an ophthalmologist to assess possible causes, which may include cataracts, glaucoma, or rare diseases such as central serous chorioretinopathy (CSCR).

Long-term application of FeniVate ointment on the face area is undesirable, since the skin in this area is more susceptible to atrophic changes. When applying FeniVeyt ointment to the eyelids, it is necessary to make sure that the drug does not get into the eyes, since repeated contact of the drug with the mucous membrane of the eye can lead to the development of cataracts and glaucoma.

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

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

Obvious suppression of HPA function (cortisol level in blood plasma in the morning less than 5 mcg/dl) in adults is unlikely when using the drug FeniVeyt in the recommended doses, except in cases when the drug is applied to more than 50% of the body surface area and in an amount of more than 20 g per day.

Influence on the ability to drive motor vehicles and manage mechanisms

No studies have been conducted to evaluate the effect of Phenyweight on the ability to drive vehicles or mechanisms. Based on the adverse reaction profile of FeniVeyt, no adverse effects on driving vehicles and mechanisms are expected.

Active ingredient

Fluticasone

Dosage form

ointment