Etacid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ETACID (ETACID)

Composition:

Active substance: mometasone;

1 spray dose contains 50 mcg of mometasone furoate;

Excipients: microcrystalline cellulose and sodium carmellose; sodium citrate; glycerin; citric acid, monohydrate; polysorbate 80; benzalkonium chloride; purified water.

Pharmaceutical form. Nasal spray, metered, suspension.

Main physicochemical characteristics: white or almost white suspension.

Pharmacotherapeutic group.

Anti-inflammatory and other drugs for local use in diseases of the nasal cavity. Corticosteroids. ATC code R01AD09.

Pharmacological Properties

Pharmacodynamics

Mometasone is a synthetic corticosteroid for topical use that exerts a pronounced anti-inflammatory effect. The local anti-inflammatory action of mometasone occurs at doses at which systemic effects do not occur.

The main mechanism of mometasone's anti-inflammatory and antiallergic action is related to its ability to suppress the release of mediators of allergic reactions. It significantly reduces the synthesis/release of leukotrienes from leukocytes of patients suffering from allergic diseases. In cell culture studies, it demonstrated 10 times greater activity than other steroids, including beclomethasone, betamethasone, hydrocortisone, and dexamethasone, in inhibiting the synthesis/release of IL-1, IL-5, IL-6, and TNFα. It is also a potent inhibitor of Th2 cytokine production, specifically IL-4 and IL-5, from human CD4+ T-cells. Mometasone is also 6 times more active than beclomethasone and betamethasone in suppressing IL-5 production.

In challenge studies involving antigen application to the nasal mucosa, intranasal mometasone demonstrated high anti-inflammatory activity in both the early and late phases of the allergic response. This was confirmed by a reduction (compared to placebo) in histamine levels and eosinophil activity, as well as a decrease (compared to baseline) in the number of eosinophils, neutrophils, and epithelial cell adhesion proteins.

Pronounced clinical effect within the first 12 hours of intranasal mometasone use was achieved in 28% of patients with seasonal allergic rhinitis. On average (50%), symptom relief occurred within 35.9 hours. In addition, it demonstrated significant efficacy in reducing ocular symptoms (redness, tearing, itching) in patients with seasonal allergic rhinitis.

In clinical trials involving patients with nasal polyps, intranasal mometasone demonstrated significant clinical efficacy in relieving nasal congestion, reducing polyp size, and restoring the sense of smell compared to placebo.

In clinical studies involving patients aged 12 years and older, intranasal mometasone at a dose of 200 mcg twice daily demonstrated high efficacy in alleviating rhinosinusitis symptoms compared to placebo. Over 15 days of treatment, rhinosinusitis symptoms were assessed using the Major Symptom Score (MSS) scale (facial pain, pressure in the nasal sinuses, tenderness upon palpation, pain in the sinus area, rhinorrhea, postnasal drip, and nasal congestion). The efficacy of amoxicillin 500 mg three times daily did not significantly differ from placebo in alleviating rhinosinusitis symptoms on the MSS scale. During the post-treatment follow-up period, the number of recurrences in the intranasal mometasone group was low and comparable to the amoxicillin and placebo groups. Treatment duration for acute rhinosinusitis exceeding 15 days was not evaluated.

Children

During a one-year placebo-controlled clinical trial in which children (n=49/group) received mometasone furoate 100 mcg once daily, no suppression of growth velocity was observed.

Data on the safety and efficacy of mometasone furoate in children aged 3 to 5 years are limited; therefore, an appropriate dosing range cannot be established.

In a study involving 48 children aged 3 to 5 years who received intranasal mometasone furoate at doses of 50, 100, or 200 mcg daily for 14 days, no significant differences compared to placebo were observed in the mean change in plasma cortisol levels in response to tetracosactrin stimulation testing.

Pharmacokinetics

Absorption

The bioavailability of mometasone when administered as a nasal spray is <1% in plasma (based on data obtained using a sensitive method with a lower limit of quantification of 0.25 pg/mL).

Distribution

Mometasone is very poorly absorbed via the nasal route.

Metabolism

Any small amount of the spray that may be swallowed and absorbed is completely metabolized during first-pass metabolism in the liver.

Excretion

Absorbed mometasone is completely metabolized, and metabolites are excreted in urine and bile.

Clinical characteristics.

Indications.

• Treatment of seasonal or perennial allergic rhinitis in adults and children aged 3 years and older (prophylactic treatment of moderate to severe allergic rhinitis should be initiated 4 weeks before the anticipated start of pollen season).
• As an adjunctive therapeutic agent in antibiotic treatment of acute episodes of sinusitis in adults (including elderly patients) and children aged 12 years and older.
• Treatment of symptoms of acute rhinosinusitis without signs of severe bacterial infection in adults and children aged 12 years and older.
• Treatment of nasal polyps and associated symptoms, including nasal congestion and loss of smell, in patients aged 18 years and older.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• Use of the medicinal product in the presence of untreated localized infection involving the nasal mucosa, such as herpes simplex.
• Use in patients who have recently undergone nasal surgery or who have sustained nasal trauma until healing has occurred (due to the wound-healing suppression effect of corticosteroids).

Interaction with other medicinal products and other forms of interaction.

Concomitant use of topical mometasone with CYP3A inhibitors, including medicinal products containing cobicistat, increases the risk of systemic adverse reactions. Concomitant use of these medicinal products should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects. In such cases, patients should be monitored for the occurrence of systemic corticosteroid adverse reactions.

When topical mometasone was administered concomitantly with a non-sedating oral antihistamine (loratadine), the pharmacokinetic parameters and safety profile remained unchanged for both medicinal products.

Special precautions for use.

The medicinal product should not be used in the presence of untreated local infection involving the nasal mucosa.

The medicinal product should not be used in patients who have recently undergone nasal surgery or have sustained nasal trauma until healing has occurred, as corticosteroids (including mometasone) may impair wound healing.

The medicinal product should be used with caution or avoided altogether in patients with active or latent tuberculosis of the respiratory tract, as well as in those with untreated fungal, bacterial, systemic viral infections, or herpes simplex infection involving the eyes.

Patients receiving corticosteroids (including mometasone) may have reduced immune responsiveness and should therefore be warned about the increased risk of contracting certain infectious diseases (e.g., chickenpox, measles) upon exposure, and advised to consult a physician if such exposure occurs.

Patients using the medicinal product for several months should undergo periodic examinations to detect possible changes in the nasal mucosa.

In clinical studies, no signs of atrophy of the nasal mucosa were observed after 12 months of intranasal mometasone use; furthermore, mometasone contributed to the normalization of the histological picture of the nasal mucosa. If local fungal infection of the nose or pharynx develops, discontinuation of the medicinal product or appropriate antifungal treatment may be required. Persistent irritation of the nasal or pharyngeal mucosa may also be an indication for discontinuing treatment.

The medicinal product is not recommended for use in cases of nasal septum perforation (see section "Side effects").

In clinical trials, a higher incidence of epistaxis (nosebleeds) was observed with intranasal mometasone compared to placebo. These nosebleeds were self-limiting and mild in severity (see section "Side effects").

With prolonged use of intranasal corticosteroids, particularly at high doses, systemic effects may occur. These effects are much less likely than with oral corticosteroids and may vary between individual patients and different corticosteroid products. They include: Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma, and, more rarely, a range of psychological or behavioral changes such as psychomotor hyperactivity, sleep disturbances, restlessness, depression, or aggression (particularly in children).

Cases of increased intraocular pressure have been reported during treatment with intranasal corticosteroids (see section "Side effects").

Visual disturbances may occur with both systemic and locally acting corticosteroids (including intranasal, inhaled, and intraocular administration). If symptoms such as blurred vision or other visual disturbances occur, patients should be referred to an ophthalmologist to evaluate possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after both systemic and local corticosteroid use.

Patients transitioning to nasal spray therapy after prolonged systemic corticosteroid treatment require close monitoring. Discontinuation of systemic corticosteroids in these patients may lead to adrenal insufficiency. If these patients exhibit signs and symptoms of adrenal insufficiency or withdrawal syndrome (e.g., joint and/or muscle pain, fatigue, depression), despite resolution of nasal symptoms, systemic corticosteroid therapy should be reinstated along with other appropriate treatments. Allergic conditions previously suppressed by systemic corticosteroid therapy, such as allergic conjunctivitis or eczema, may also become apparent during this transition.

Use of doses higher than recommended may result in clinically significant adrenal suppression. If there is evidence of doses exceeding the recommended levels, additional systemic corticosteroid coverage should be considered during periods of stress or elective surgery.

Prolonged or high-dose corticosteroid therapy may lead to systemic effects such as growth suppression in children. The long-term effects of intranasal/inhaled corticosteroids (including mometasone) in children are not fully understood.

In a one-year study of 49 children receiving intranasal mometasone at a dose of 100 mcg daily, no growth retardation was observed. However, growth should be carefully monitored in children receiving long-term corticosteroid therapy. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of the nasal corticosteroid, if possible, to the lowest effective dose that maintains adequate symptom control. Additionally, the patient should be referred for pediatric consultation.

Patients with acute rhinosinusitis should seek immediate medical attention if signs or symptoms of severe bacterial infection develop, such as fever, severe unilateral facial pain or toothache, orbital or periorbital swelling/edema, or worsening condition after initial improvement.

Although the medicinal product controls nasal symptoms in most patients, concomitant use of appropriate additional therapy may further alleviate other symptoms, particularly ocular symptoms.

The safety and efficacy of intranasal mometasone in the treatment of unilateral nasal polyps, polyps associated with cystic fibrosis, or polyps completely obstructing the nasal cavity have not been studied. Unilateral nasal polyps, which are unusual and rare, especially when associated with ulceration or bleeding, should be investigated further.

The safety and efficacy of intranasal mometasone in the treatment of nasal polyps in children and adolescents under 18 years of age have not been established.

The safety and efficacy of intranasal mometasone in the treatment of rhinosinusitis symptoms in children under 12 years of age have not been established.

The medicinal product contains benzalkonium chloride as a preservative, which may cause irritation or swelling inside the nose, particularly with prolonged use.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the effects of mometasone during pregnancy are limited or lacking. Animal studies have shown reproductive toxicity. As with other intranasal corticosteroids, the medicinal product should be used during pregnancy only if the potential benefit justifies the potential risk to the mother, fetus, or infant. Infants born to mothers who used corticosteroids during pregnancy should be carefully monitored for possible adrenal insufficiency.

Breastfeeding

It is unknown whether mometasone passes into breast milk. As with other intranasal corticosteroids, a decision should be made whether to discontinue breastfeeding or to discontinue/abstain from treatment, taking into account the benefits of breastfeeding for the child and the therapeutic benefit for the mother.

Fertility

Clinical data on the effect of mometasone on fertility are lacking. Animal studies have shown reproductive toxicity, but no effect on fertility.

Ability to affect reaction speed when driving vehicles or operating machinery.

Unknown.

Method of Administration and Dosage

Dosage

Treatment of seasonal or perennial allergic rhinitis

Adults (including elderly) and children aged 12 years and older:

The recommended prophylactic and therapeutic dose is 2 sprays (50 mcg each) into each nostril once daily (total daily dose – 200 mcg).

After achieving the therapeutic effect, the dose should be reduced for maintenance therapy to 1 spray into each nostrid 1 time daily (total daily dose – 100 mcg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to the maximum: 4 sprays into each nostril once daily (total daily dose – 400 mcg). After symptom relief is achieved, dose reduction is recommended.

In some patients with seasonal allergic rhinitis, a clinically significant onset of action may occur within 12 hours after the first administration. However, full benefit from treatment may not be achieved within the first 48 hours; therefore, patients should continue regular use of the medication to achieve full therapeutic effect.

Children aged 3 to 11 years:

The recommended therapeutic dose is 1 spray (50 mcg) into each nostril once daily (total daily dose – 100 mcg).

Adjunctive treatment of acute sinusitis episodes

Adults (including elderly) and children aged 12 years and older:

The recommended therapeutic dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to 4 sprays into each nostril twice daily (total daily dose – 800 mcg).

After symptom relief is achieved, dose reduction is recommended.

Treatment of acute rhinosinusitis symptoms

Adults and children aged 12 years and older:

The recommended therapeutic dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg).

Treatment of nasal polyps

Adults (including elderly):

The recommended therapeutic dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg).

After achieving clinical response, the dose should be reduced to 2 sprays into each nostril once daily (total daily dose – 200 mcg).

Method of Administration

The medication is intended for intranasal use.

Before each administration, the nose should be thoroughly cleared of mucus.

Before using a new bottle for the first time, it must be primed. Priming is performed by approximately 10 actuations of the spray pump, which ensures consistent delivery of the medication, with each spray releasing approximately 100 mg of suspension containing 50 mcg of mometasone (1 dose). If the nasal spray has not been used for 14 days or longer, the device must be re-primed by spraying 2 times until a full spray is observed before the next use. Do not pierce the nozzle before initial use.

The bottle should be shaken vigorously before each use.

If the nozzle becomes clogged, remove the plastic cap by pressing gently on the white ring, carefully remove the nozzle, rinse it with warm running water, dry it thoroughly, and reattach it. Do not attempt to clear the nozzle with a needle or any other sharp object, as this may damage the spray pump. Regular cleaning of the nozzle is very important.

Children.

No growth suppression has been observed in children treated with a daily dose of 100 mcg for one year.

The safety and efficacy of intranasal mometasone for the treatment of nasal polyps in children and adolescents (under 18 years of age), rhinosinusitis symptoms in children under 12 years of age, and seasonal or perennial allergic rhinitis in children under 3 years of age have not been established.

Overdose.

Inhalation or oral administration of excessive doses of corticosteroids may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Due to the low systemic bioavailability of intranasal mometasone (< 1%), it is unlikely that any measures other than patient monitoring and subsequent administration of the medication at the recommended dose will be required in case of overdose.

Adverse Reactions

In clinical trials of allergic rhinitis, nasal bleeding was mainly self-limiting, mild, and occurred slightly more frequently than with placebo (5%), but was comparable to or less frequent than with other investigated intranasal corticosteroids used as active controls (up to 15%). The incidence of other adverse reactions was similar to that observed with placebo. In patients with nasal polyps, the overall incidence of adverse reactions was similar to that observed in patients with allergic rhinitis.

Systemic effects of intranasal corticosteroids are more likely to occur with high-dose and long-term use.

Adverse reactions are classified by system organ class and frequency of occurrence. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); frequency not known (cannot be estimated based on available data). The frequency of adverse reactions observed in post-marketing studies is categorized as "frequency not known" (cannot be estimated based on available data).

Adverse reactions observed during clinical trials in patients with allergic rhinitis or nasal polyposis and during post-marketing use

Infections and infestations:

common – pharyngitis, upper respiratory tract infections¹.

Immune system disorders:

frequency not known – hypersensitivity reactions, including anaphylactic reactions, angioedema, bronchospasm, and dyspnea.

Nervous system disorders:

common – headache.

Eye disorders:

frequency not known – glaucoma, increased intraocular pressure, cataract, blurred vision.

Respiratory, thoracic and mediastinal disorders:

very common – epistaxis²; common – epistaxis, nasal mucosal burning sensation, nasal mucosal irritation, nasal mucosal ulceration; frequency not known – nasal septum perforation.

Gastrointestinal disorders:

common – throat irritation²; frequency not known – taste and smell disturbances.

¹ Observed uncommonly when administered twice daily for the treatment of nasal polyposis.
² Observed when administered twice daily for the treatment of nasal polyposis.

Children

In children, the incidence of reported adverse reactions during clinical trials—such as epistaxis (6%), headache (3%), nasal mucosal irritation (2%), and sneezing (2%)—was comparable to that observed with placebo.

Adverse reactions observed during clinical trials in patients with acute rhinosinusitis

Respiratory, thoracic and mediastinal disorders:

common – epistaxis.

Gastrointestinal disorders:

common – abdominal pain, diarrhea, nausea.

General disorders and administration site conditions:

common – headache.

The most common adverse reaction, epistaxis, occurred at approximately similar frequencies in the placebo group (2.6%) and the intranasal mometasone group (2.9% and 3.7%, respectively).

Systemic effects of intranasal corticosteroids may occur, particularly with prolonged use of high doses.

Cases of glaucoma/increased intraocular pressure have been reported with the use of intranasal corticosteroids.

During post-marketing use, blurred vision has been reported.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is highly important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25°C, in a place inaccessible to children. Do not freeze.

Packaging.

18 g (140 doses) in a white opaque polyethylene bottle with a metering device and protective cap, or in an amber glass bottle with a metering device, protective cap, and safety clip; 1 bottle with the instruction for medical use in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

UORLД MEDICIN ILAC SAN. VE TIC. A.S. /
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and place of business.

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.

Marketing authorization holder.

WORLD MEDICINE, LLC, Ukraine.