FeniVeit, ointment 0.005% 15 g

Due to limited absorption of fluticasone through the skin, the bioavailability of the drug when used externally is very low. The bioavailability of fluticasone when ingested is close to zero due to very low gastrointestinal absorption and extensive metabolism during “first passage” through the liver, which ensures low systemic exposure if the drug is accidentally swallowed.

Distribution

After entering the systemic bloodstream, fluticasone rapidly enters the bile and is excreted through the intestine. The degree of binding to plasma proteins is quite high (91%). 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 excretion from the body. Thus, the drug, having entered through the skin into the systemic bloodstream, is quickly inactivated. The main route of metabolism is hydrolysis to carboxylic acid; this metabolite has very weak glucocorticosteroid and anti-inflammatory activity.

Elimation

The excretion rate of intravenously administered fluticasone propionate is linear over a dose range of 250 to 1000 µg and is characterized by a high blood plasma clearance (CL=1.1 L/min).

The maximum plasma concentrations are reduced by approximately 98% within 3-4 hours, and only low plasma concentrations have been associated with a final 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. The anti-inflammatory properties are due to multiple mechanisms of inhibition of the late phase of allergic reactions, including reduction of mast cell number, attenuation of eosinophil chemotaxis and activation, reduction of cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibition of arachidonic acid metabolism.

Fluticasone is a glucocorticosteroid (GCS) with a strong 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 has high selectivity and affinity for glucocorticosteroid receptors.

The fluticasone propionate-receptor complex stimulates or inhibits iRNA transcription and subsequent protein synthesis. The production of enzymes responsible for the anti-inflammatory effect is increased while the production of inflammatory mediators is reduced.

The production of enzymes responsible for the anti-inflammatory action is increased while the production of inflammatory mediators is decreased. When applied to the skin, there is little possibility of suppression of hypothalamic-pituitary-adrenal system (GnA) function.

According to clinical studies, if fluticasone enters systemic blood flow, it is quickly transformed in the liver to inactive metabolite (17β-carboxylic acid) with subsequent rapid excretion from the body. Due to these properties FeniVeit has a high therapeutic index.

Pharmacodynamic effects

Fluticasone does not cause unforeseen hormonal disturbances and has no significant effect on the central and peripheral nervous system, gastrointestinal tract, cardiovascular and respiratory systems.

Indications

Active ingredient

Composition

How to take, the dosage

Externally.

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

The use of the ointment is especially indicated for the treatment of dry, lichenified or flaky lesions.

Apply FeniVate ointment 1 or 2 times daily in a thin layer in an amount no more than is needed to cover the entire affected area and rub in gently 1 or 2 times a day until effective, but not for more than 4 weeks.

Please allow enough time for FeniVate ointment to absorb before applying the emollient.

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

When using fluticasone propionate, care should be taken to ensure that the minimum amount with therapeutic effect is applied. Recurrence of initial dermatosis symptoms may occur when therapy with external corticosteroids is discontinued, especially when highly active drugs are used.

Particular patient groups

Children 10 years and older

Do not use in children younger than 10 years of age. Children are more likely to have local and systemic side effects with external GCS, and in general, shorter courses of treatment and less active medications are recommended for children compared to adults.

Patient caution should be exercised when using FeniVate ointment, ensuring that the application of the drug is kept to a minimum for as short a period of time as possible to produce a clinical effect.

Patients in the elderly

There have been no differences in outcomes between the elderly and younger patient groups in clinical studies.

The higher prevalence of reduced hepatic or renal function in elderly patients may result in slower excretion of the active ingredient if it is absorbed systemically.

PheniVate ointment should therefore be applied in the smallest amount possible for the shortest amount of time sufficient to produce a clinical effect.

Patients with impaired renal and/or hepatic function

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

Interaction

Special Instructions

Manifestations of hypercorticism (Icenko-Cushing’s syndrome) and reversible inhibition of GHNS leading to glucocorticoid failure in some cases are due to increased systemic absorption of topical GCS.

In these cases, treatment should be discontinued gradually, reducing the frequency of application, or FeniVate should be replaced with a less active GCS. Sudden discontinuation of treatment may lead to glucocorticoid failure.

Risk factors for severe systemic reactions include the following:

In children 10-12 years of age, prolonged, continuous topical GCS therapy should be avoided if possible, since there is potential for inhibition of adrenal function.

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

Hence, if a patient has symptoms such as blurred vision or other visual disturbances, consideration should be given to referring the patient to an ophthalmologist for evaluation of possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR).

Long-term application of FeniVate ointment to the facial area is undesirable because the skin in this area is more prone to atrophic changes. When FeniVate ointment is applied to the eyelids, care should be taken to avoid getting it in the eyes as repeated contact with the eye mucosa could result in cataracts and glaucoma.

In case of secondary infection of skin lesions, appropriate antibiotic therapy should be administered. If there are signs of spreading infection, topical GCS should be discontinued and appropriate antibiotic therapy should be prescribed.

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

A clear inhibition of GHNS function (plasma cortisol levels less than 5 mcg/dL in the morning) in adults is unlikely with FeniVeit at the recommended doses, except when applied over 50% of the body surface area and in amounts greater than 20 g per day.

There have been no studies to evaluate the effect of FeniVeit on the ability to drive vehicles or operate machinery. Based on the profile of adverse reactions of FeniVeit no adverse effects on driving and operating machinery are expected.

Contraindications

Do not use on closed skin areas (such as diaper rash or under occlusive dressings).

With caution:

Renal insufficiency, hepatic insufficiency, old age, childhood (10 to 12 years old).

Side effects

The undesired reactions presented below are listed according to organ and organ system involvement and frequency of occurrence. The frequency of occurrence is defined as follows: Very common (≥ 1/10), common (≥ 1/100 and

Infectious and parasitic diseases: Very rare – Opportunistic infections.

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

Endocrine system disorders (GGNS inhibition): Very rare – Weight gain or obesity; Slow weight gain or stunting in children; Cushingoid features (e.g., moon-shaped face, central obesity); Decreased endogenous cortisol concentration; Hyperglycemia or glucosuria; Arterial hypertension; Osteoporosis; Cataracts; Glaucoma.

Skin and subcutaneous tissue disorders

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

Infrequent – Burning at the place of application.

very rarely – Thinning of the skin, atrophy, stretch marks, telangiectasia, changes in pigmentation, 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.

The occurrence of any of the adverse reactions noted above should be reported to the physician. The decision about further treatment strategy should be made by the physician.

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

Overdose

Symptoms

Fluticasone may be absorbed in sufficient quantities to cause systemic action when used topically. The likelihood of acute overdose is extremely low, but signs of hypercorticism (Icenko-Cushing’s syndrome) may develop with chronic overdose or improper use of FeniVate.

Treatment

In fluticasone overdose, the drug is withdrawn gradually by reducing the frequency of application or switching to a less active GCS to avoid the risk of glucocorticoid failure. If the clinical picture of drug overdose develops, symptomatic therapy is indicated.

Pregnancy use

Fertility

There are no available data to evaluate the effect of topical GCS on human fertility. No effect of fluticasone propionate on fertility has been found in animal studies.

Pregnancy

Limited data are available on the use of fluticasone during pregnancy. In studies of reproductive function in animals, adverse effects typical of strong corticosteroids were observed only at high levels of systemic exposure.

Preclinical studies have found that external use of corticosteroids in pregnant animals can cause abnormal fetal development, but the significance in humans has not been established.

The use of the drug in pregnancy is not recommended unless the benefit to the mother exceeds the potential risk to the fetus and only under medical supervision. Before using during pregnancy it is necessary to consult a doctor. The ointment should be applied in the minimum amount for the shortest possible period of time sufficient for the clinical effect to be evident.

Breastfeeding

The safety of topical GKS therapy during breastfeeding has not been established.

There are no data available to support the possibility of systemic absorption of external GCSs to an extent sufficient to be detected in breast milk.

Preclinical studies have shown that fluticasone was detected in milk during breastfeeding when administered subcutaneously in amounts sufficient to be detected in plasma.

The use of the drug during breastfeeding is not recommended unless the expected benefit to the mother outweighs any possible risks to the baby. Consult a physician before using during breastfeeding.

When using during breastfeeding, the drug should not be applied to the mammary gland area to prevent accidental ingestion by the baby.

Similarities