Rialtris mono

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RYALTRIS MONO (RYALTRISMONO)

Composition:

Active substance: mometasone furoate;

One dose contains mometasone furoate monohydrate equivalent to mometasone furoate 50 μg;

Excipients: microcrystalline cellulose and sodium carboxymethylcellulose; glycerin; citric acid, monohydrate; sodium citrate; polysorbate 80; benzalkonium chloride; water for injections.

Pharmaceutical form. Nasal spray, metered; suspension.

Main physicochemical properties: white or almost white, semi-transparent viscous suspension.

Pharmacotherapeutic group.

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

Pharmacological properties.

Pharmacodynamics.

Mometasone furoate is a synthetic corticosteroid for topical use with pronounced anti-inflammatory activity. The local anti-inflammatory effect of mometasone furoate occurs at doses that do not produce systemic effects.

The primary mechanism of the anti-inflammatory and antiallergic action of mometasone furoate is related to its ability to inhibit the release of mediators of allergic reactions. Mometasone furoate significantly reduces the synthesis/release of leukotrienes from leukocytes of patients suffering from allergic diseases. In cell culture studies, mometasone furoate demonstrated 10-fold greater activity than other steroids, including beclomethasone dipropionate, betamethasone, hydrocortisone, and dexamethasone, in suppressing 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 furoate is also 6 times more potent than beclomethasone dipropionate and betamethasone in inhibiting IL-5 production.

In challenge studies involving antigen application to the nasal mucosa, the aqueous nasal spray of mometasone furoate demonstrated high anti-inflammatory activity in both the early and late phases of the allergic reaction. 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.

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

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

In clinical studies involving patients aged 12 years and older, the nasal spray of mometasone furoate at a dose of 200 mcg twice daily demonstrated high efficacy in alleviating symptoms of rhinosinusitis compared to placebo. Over 15 days of treatment, rhinosinusitis symptoms were assessed using the Major Symptom Score (MSS) scale (facial pain, pressure in 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 follow-up period after treatment completion, the recurrence rate in the mometasone furoate group was low and comparable to the amoxicillin and placebo groups. Treatment duration for acute rhinosinusitis exceeding 15 days was not evaluated.

Pharmacokinetics.

The systemic bioavailability of mometasone furoate following administration 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). Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract, and any small amount that may be swallowed and absorbed undergoes extensive first-pass metabolism prior to excretion, primarily in the form of metabolites via bile and to a lesser extent via urine.

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 expected start of the 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 mometasone furoate or to any of the excipients of the medicinal product.

Untreated local infection of the nasal mucosa.

Nasal trauma or recent nasal surgery.

Interaction with other medicinal products and other forms of interaction.

Concomitant therapy with CYP3A inhibitors, including medicinal products containing cobicistat, is expected to increase the risk of systemic adverse effects. Concomitant use should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid-related adverse effects; in such cases, patients should be monitored for the occurrence of systemic corticosteroid-related adverse effects.

In a clinical study, mometasone furoate 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 product should not be used in the presence of untreated localized infection involving the nasal mucosa.

Since corticosteroids may impair wound healing, intranasal corticosteroids should not be administered to patients who have recently undergone nasal surgery or who have sustained nasal trauma until healing has occurred.

Ryaltris Mono should be used with caution or not used at all in patients with active or latent tuberculosis infections of the respiratory tract, as well as in patients with untreated fungal, bacterial, systemic viral infections, or herpes simplex infection affecting the eyes.

As with any long-term therapy, patients treated with this medicinal product for several months or longer should be periodically examined for possible changes in the nasal mucosa. In clinical studies, 12 months of treatment with mometasone furoate did not result in signs of nasal mucosal atrophy; furthermore, mometasone furoate contributed to the normalization of the histological appearance of the nasal mucosa.

If a local fungal infection of the nose or throat develops, treatment with the product may need to be discontinued or appropriate antifungal therapy initiated. Persistent irritation of the nasal or pharyngeal mucosa may also be an indication for discontinuation of treatment with the product.

There is no evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression with long-term treatment with mometasone furoate. However, prolonged use of intranasal corticosteroids (including Ryaltris Mono) may affect adrenal cortex function and may lead to hypercortisolism in corticosteroid-sensitive patients and in certain cases. Patients who are switched to treatment with Ryaltris Mono after prolonged systemic corticosteroid therapy should be closely monitored, as they may develop adrenal insufficiency.

The safety and efficacy of mometasone furoate 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 uncommon and rarely occur, especially when associated with ulceration or bleeding, should be investigated further.

Patients receiving corticosteroids may have potentially reduced immune responsiveness and should be warned about the increased risk of infection when exposed to certain infectious diseases (e.g., chickenpox, measles). They should also be advised to seek medical advice if such exposure occurs.

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

When switching from systemic corticosteroid therapy to treatment with Ryaltris Mono, some patients may experience symptoms of corticosteroid withdrawal despite improvement in nasal symptoms. Such patients should be specifically reassured about the appropriateness of continuing treatment with Ryaltris Mono.

Changing therapy may also unmask allergic conditions that were previously suppressed by systemic corticosteroid therapy.

The use of high doses or prolonged use of glucocorticosteroids may cause systemic effects, such as growth suppression in children. The long-term effects of intranasal/inhaled steroids in children are not fully understood. Physicians should generally monitor the growth of children receiving long-term glucocorticosteroid therapy. In a study of 49 children treated with mometasone furoate at a dose of 100 mcg daily for one year, no growth suppression was observed.

Cases of increased intraocular pressure have been reported after the use of intranasal corticosteroids.

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

Acute rhinosinusitis: Patients should be advised to seek immediate medical attention if signs or symptoms of severe bacterial infection occur, such as fever, severe unilateral facial pain or toothache, orbital or periorbital swelling/edema, or worsening condition after initial improvement.

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

Use during pregnancy or breastfeeding

Systemic (subcutaneous) corticosteroids have been shown to be teratogenic in animals. Clinical studies in pregnant or breastfeeding women have not been conducted.

Corticosteroid medicinal products should not be used during pregnancy or breastfeeding unless clearly necessary.

Ability to affect reaction speed when driving or operating machinery

Unknown.

Method of Administration and Dosage.

The product is intended for intranasal use only.

Seasonal or Perennial Allergic Rhinitis: The recommended prophylactic and therapeutic dose for adults (including elderly patients) and children aged 12 years and older 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 to 1 spray into each nostrid once daily (total daily dose – 100 mcg) for maintenance therapy.

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.

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

For 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. For adults (including elderly patients) 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.

Acute Rhinosinusitis. For 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).

Nasal Polyps. For patients aged 18 years and older (including elderly patients), the recommended dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg). After achieving the clinical effect, the dose should be reduced to 2 sprays into each nostril once daily (total daily dose – 200 mcg). If no clinical effect is observed after 5–6 weeks of treatment with the recommended doses, alternative therapy should be considered.

Administration of Nasal Spray

Shake the bottle vigorously before each use. Then remove the protective cap. Before first use, the bottle must be primed. Priming is performed by approximately 10 actuations of the dosing device, which establishes consistent delivery of the medication, such that each actuation delivers approximately 100 mg of suspension containing 50 mcg of mometasone (one dose). If the nasal spray has not been used for 14 days or longer, it must be re-primed by 2 actuations until a full spray is observed. Do not pierce the nozzle before starting use.

Before each administration, the nose should be cleared thoroughly of mucus. After clearing the nasal passages, spray the suspension into each nostril while keeping the head slightly tilted forward. After use, wipe the spray nozzle, and cover it with the protective cap.

Cleaning the Spray Nozzle

1. Remove the protective cap.
2. Gently pull upward on the white body of the spray nozzle, carefully detach it, and soak the nozzle together with the cap in warm water for several minutes.
3. Rinse the cap and nozzle under warm running water, dry them, and reinstall in place.

Repeat the procedure until the spray nozzle is completely clean.

Do not attempt to clean the nozzle with a needle or any other sharp object, as this may damage the dispenser.

Regular cleaning of the nozzle is very important.

Children.

In placebo-controlled clinical trials in children who received mometasone furoate nasal spray at a daily dose of 100 mcg for one year, no growth suppression was observed.

The safety and efficacy of the product in the treatment of nasal polyps in children and adolescents (under 18 years of age), symptoms of rhinosinusitis 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.

Due to the low systemic bioavailability of the product (less than 1%, based on results from a sensitive quantitative method with a lower limit of quantification of 0.25 pg/mL), it is unlikely that any measures other than patient monitoring and subsequent administration of the product at the recommended dose will be required in case of overdose.

Inhalation or oral administration of high doses of corticosteroids over a prolonged period may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Adverse reactions.

Treatment-related adverse reactions observed in clinical studies with mometasone furoate in patients with allergic rhinitis are listed in Table 1.

Table 1

Nasal bleeding stopped spontaneously and was mild, occurring somewhat more frequently than with placebo (5%), but less frequently than with other investigational intranasal corticosteroids used as active controls (in some of these, the incidence of nasal bleeding was up to 15%). The incidence of other adverse events was comparable to that observed with placebo.

In children, the incidence of adverse events was comparable to that with placebo, for example, nasal bleeding (6%), headache (3%), nasal irritation (2%), and sneezing (2%).

In patients with nasal polyps, the overall number of adverse events was comparable to that with placebo and similar to the number observed in patients with allergic rhinitis.

Treatment-related adverse reactions observed with mometasone furoate in clinical trials in more than 1% of patients are listed in Table 2.

Table 2

After intranasal administration of mometasone furoate, hypersensitivity reactions, including bronchospasm and dyspnea, may occasionally occur. Very rarely, anaphylactic reactions, angioneurotic edema, or disturbances of smell and taste have been reported.

In patients with acute rhinosinusitis, the overall incidence of adverse events was comparable to that with placebo and similar to the incidence observed in patients with other indications.

Treatment-related adverse reactions observed in clinical trials in more than 2% of patients are listed in Table 3.

Table 3

The most common adverse reaction, nasal bleeding, occurred at approximately the same frequency in the placebo group (2.6%) and in the mometasone furoate group (2.9% and 3.7%, respectively).

Systemic effects of intranasal corticosteroids may occur, especially with high doses used over prolonged periods.

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

Blurred vision has been reported.

Shelf life.

2 years.

Storage conditions.

Store in a light-protected place at a temperature not exceeding 30 °C. Do not freeze. Keep out of the reach of children.

Packaging.

60 or 120 doses in a polyethylene bottle. One bottle with a metering pump-spray device, closed with a cap, in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Glenmark Pharmaceuticals Ltd./Glenmark Pharmaceuticals Ltd.

Manufacturer's address and location of business operations.

Unit III, Village Kishanpura, Baddi-Nalagarh Road, Tehsil Baddi, Distt. Solan (H.P.) 173 205, India/
Unit III, Village Kishanpura, Baddi-Nalagarh Road, Tehsil Baddi, Distt. Solan (H.P.) 173 205, India.