Nasonex^® (Spray) Instructions for Use

Marketing Authorization Holder

Organon Heist, BV (Belgium)

Manufactured By

Schering-Plough Labo N.V. (Belgium)

Packaging and Quality Control Release

SCHERING-PLOUGH LABO, N.V. (Belgium)

Or

AKRIKHIN Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

MSD Pharmaceuticals LLC (Russia)

ATC Code

R01AD09 (Mometasone)

Active Substance

Mometasone (Rec.INN registered by WHO)

Dosage Forms

	Nasonex®	Nasal spray, metered dose 50 mcg/1 dose: 10 g bottle (60 doses) 1 pc. or 15 g bottle (120 doses) 1, 2, 3 pcs. in a set with a dosing device
		Nasal spray, metered dose 50 mcg/1 dose: 10 g bottle (60 doses) 1 pc. or 15 g bottle (120 doses) 1, 2, 3 pcs. in a set with a dosing device

Dosage Form, Packaging, and Composition

Nasal spray, metered dose 50 mcg/1 dose as a white or almost white suspension.

Excipients: dispersed cellulose (microcrystalline cellulose, treated with carmellose sodium) – 20 mg, glycerol – 21 mg, citric acid monohydrate – 2 mg, sodium citrate dihydrate – 2.8 mg, polysorbate 80 – 0.1 mg, benzalkonium chloride (as a 50% solution) – 0.2 mg, purified water – 0.95 g.

10 g (60 doses) – polyethylene bottles (1) in a set with a dosing device – cardboard packs.
18 g (120 doses) – polyethylene bottles (1) in a set with a dosing device – cardboard packs.
18 g (120 doses) – polyethylene bottles (2) in a set with a dosing device – cardboard packs.
18 g (120 doses) – polyethylene bottles (3) in a set with a dosing device – cardboard packs.

Clinical-Pharmacological Group

Intranasal corticosteroids

Pharmacotherapeutic Group

Drugs for the treatment of nasal diseases; decongestants and other preparations for topical use; corticosteroids

Pharmacological Action

Synthetic glucocorticosteroid for topical application. It has anti-inflammatory and anti-allergic effects when used in doses that do not cause systemic effects.

It inhibits the release of inflammatory mediators. Increases the production of lipomodulin, which is an inhibitor of phospholipase A, which causes a decrease in the release of arachidonic acid and, consequently, inhibition of the synthesis of arachidonic acid metabolites – cyclic endoperoxides, prostaglandins. Prevents marginal accumulation of neutrophils, which reduces inflammatory exudate and the production of lymphokines, inhibits macrophage migration, and leads to a decrease in infiltration and granulation processes. Reduces inflammation by reducing the formation of chemotaxis substance (effect on late allergic reactions), inhibits the development of an immediate-type allergic reaction (due to inhibition of the production of arachidonic acid metabolites and a decrease in the release of inflammatory mediators from mast cells).

In studies with provocative tests with antigen application to the nasal mucosa, high anti-inflammatory activity of mometasone was demonstrated, both in the early and late stages of the allergic reaction. This was confirmed by a decrease (compared to placebo) in the concentration of histamine and eosinophil activity, as well as a decrease (compared to baseline) in the number of eosinophils, neutrophils, and epithelial cell adhesion proteins.

Pharmacokinetics

Absorption

With intranasal use, the systemic bioavailability of mometasone furoate is <1% (with a method sensitivity of 0.25 pg/ml).

Mometasone is very poorly absorbed from the gastrointestinal tract.

Metabolism and Excretion

The small amount of active substance that may enter the gastrointestinal tract after intranasal administration undergoes active metabolism during the “first pass” through the liver. It is excreted in urine and bile.

Indications

• Seasonal and perennial allergic rhinitis in adults, adolescents, and children from 2 years of age;
• Acute sinusitis or exacerbation of chronic sinusitis in adults (including the elderly) and adolescents from 12 years of age – as an auxiliary therapeutic agent in antibiotic treatment;
• Acute rhinosinusitis with mild and moderate symptoms without signs of severe bacterial infection in patients aged 12 years and older;
• Prevention of seasonal allergic rhinitis of moderate and severe course in adults and adolescents from 12 years of age (recommended to start 2-4 weeks before the expected start of the pollen season);
• Nasal polyposis accompanied by impaired nasal breathing and sense of smell in adults (from 18 years of age).

ICD codes

Dosage Regimen

The drug is used intranasally.

Treatment of seasonal or perennial allergic rhinitis

Adults (including elderly patients) and adolescents from 12 years of age

The recommended prophylactic and therapeutic dose of the drug is 2 sprays (50 mcg of mometasone furoate each) into each nostril once a day (total daily dose – 200 mcg). Once the therapeutic effect is achieved, for maintenance therapy, it is possible to reduce the dose to 1 spray into each nostril once a day (total daily dose – 100 mcg).

If a reduction in disease symptoms is not achieved by using the drug at the recommended therapeutic dose, the daily dose may be increased to 4 sprays into each nostril once a day (total daily dose – 400 mcg). After a reduction in disease symptoms, a dose reduction is recommended.

The onset of action of the drug is usually noted clinically as early as 12 hours after the first application.

Children aged 2 to 11 years

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

Adult assistance is required for the use of the drug in young children.

Adjuvant treatment of acute sinusitis or exacerbation of chronic sinusitis

Adults (including elderly patients) and adolescents from 12 years of age

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

If a reduction in disease symptoms is not achieved by using the drug at the recommended therapeutic dose, the daily dose may be increased to 4 sprays into each nostril twice a day (total daily dose – 800 mcg). After a reduction in disease symptoms, a dose reduction is recommended.

Treatment of acute rhinosinusitis without signs of severe bacterial infection

The recommended dose for adults and adolescents is 2 sprays (50 mcg of mometasone furoate each) into each nostril twice a day (total daily dose 400 mcg). If symptoms worsen during treatment, specialist consultation is necessary.

Treatment of nasal polyposis

For adults (including elderly patients) from 18 years of age, the recommended therapeutic dose is 2 sprays (50 mcg of mometasone furoate each) into each nostril twice a day (total daily dose – 400 mcg).

After a reduction in disease symptoms, it is recommended to reduce the dose to 2 sprays (50 mcg of mometasone furoate each) into each nostril once a day (total daily dose – 200 mcg).

Rules for using the Nasonex^® drug

Spraying of the suspension contained in the bottle is carried out using a special dosing nozzle on the bottle.

Before the first use of the Nasonex^® nasal spray, it is necessary to calibrate it by pressing the dosing nozzle 10 times or until a uniform spray appears, which indicates the readiness of the drug for use. The nasal applicator should not be pierced.

The head should be tilted and the medication should be sprayed into each nostril as recommended by the attending physician.

If the medication has not been used for 14 days or longer, it is necessary to press the dosing nozzle 2 times or until a uniform spray appears.

The bottle should be shaken vigorously before each use.

Cleaning the dosing nozzle

It is important to regularly clean the dosing nozzle to avoid its malfunction. Remove the dust protection cap, then carefully remove the spray tip. Thoroughly rinse the spray tip and dust protection cap in warm water and rinse under the tap.

Do not attempt to open the nasal applicator with a needle or other sharp object, as this will damage the applicator, resulting in an incorrect dose of the drug.

The cap and tip should be dried in a warm place. After that, attach the spray tip to the bottle and screw the dust protection cap back onto the bottle. When using the nasal spray for the first time after cleaning, it is necessary to recalibrate by pressing the dosing nozzle 2 times.

Adverse Reactions

Use of the drug in clinical studies

Adverse events associated with the use of the drug (≥1%), identified during clinical studies in patients with allergic rhinitis or nasal polyposis, and during the post-registration period of the drug’s use, regardless of the indication for use, are presented in Table 1. Adverse reactions are listed according to the MedDRA system-organ class classification. Within each system-organ class, adverse reactions are classified by frequency of occurrence.

Nosebleeds were generally moderate and self-limiting, their incidence was somewhat higher than with placebo (5%), but equal to or less than with other intranasal corticosteroids used as active control (in some of them, the incidence of nosebleeds was up to 15%). The incidence of all other adverse events was comparable to their incidence when placebo was prescribed.

The overall incidence of adverse events in patients receiving treatment for nasal polyposis was comparable to the incidence in patients with allergic rhinitis.

The overall incidence of adverse events in patients receiving treatment for acute rhinosinusitis was comparable to the incidence in patients with allergic rhinitis and when placebo was prescribed.

When using intranasal corticosteroids, systemic side effects may develop, especially with long-term use of intranasal corticosteroids in high doses (see the “Special Precautions” section).

Table 1

* Identified with “uncommon” frequency when using the drug twice a day for nasal polyposis.

** Identified when using the drug twice a day for nasal polyposis.

Children

Respiratory system: epistaxis (6%), nasal mucosal irritation (2%), sneezing (2%).

Nervous system: headache (3%).

The incidence of these adverse events in children was comparable to their incidence when placebo was used.

Post-registration use of the drug

During the post-registration use of the Nasonex^® drug, the following adverse reactions were additionally identified: blurred vision.

Contraindications

• Hypersensitivity to any of the substances included in the drug;
• Recent surgery or nasal trauma with damage to the nasal mucosa – until the wound heals (due to the inhibitory effect of corticosteroids on healing processes);
• Childhood age (for seasonal and perennial allergic rhinitis – up to 2 years, for acute sinusitis or exacerbation of chronic sinusitis – up to 12 years, for polyposis – up to 18 years) – due to the lack of relevant data.

With caution, the drug should be used in cases of tuberculosis infection (active or latent) of the respiratory tract, untreated fungal, bacterial, systemic viral infection, or infection caused by Herpes simplex with eye involvement (as an exception, the drug may be prescribed for the listed infections as directed by a doctor), the presence of an untreated local infection involving the nasal mucosa.

Use in Pregnancy and Lactation

Appropriately planned and well-controlled studies of the drug in pregnant women have not been conducted.

As with the use of other intranasal corticosteroids, the Nasonex^® drug should be prescribed to pregnant or breastfeeding women only if the expected benefit from prescribing the drug justifies the potential risk to the fetus or infant.

Infants whose mothers received corticosteroids during pregnancy should be carefully monitored for the possible development of hypoadrenalism.

Pediatric Use

Contraindicated in seasonal and perennial allergic rhinitis – in children under 2 years of age, in acute sinusitis or exacerbation of chronic sinusitis – under 12 years of age, in polyposis – under 18 years of age (due to the lack of relevant data).

Special Precautions

As with any long-term treatment, patients using the Nasonex^® nasal spray for several months or longer should periodically undergo examination by a doctor for possible changes in the nasal mucosa. Patients receiving intranasal corticosteroids for a long time should be monitored. Growth retardation may develop in children. If growth retardation is detected in children, it is necessary to reduce the dose of intranasal corticosteroids to the minimum that effectively controls the symptoms. In addition, the patient should be referred for consultation with a pediatrician.

If a local fungal infection of the nose or pharynx develops, it may be necessary to discontinue therapy with the Nasonex^® nasal spray and carry out specific treatment. Persistent irritation of the nasal and pharyngeal mucosa may also be a reason to discontinue treatment with the Nasonex^® nasal spray.

In placebo-controlled clinical studies in children, when the Nasonex^® nasal spray was used at a daily dose of 100 mcg for one year, no growth retardation was observed in children.

During long-term treatment with the Nasonex^® nasal spray, no signs of suppression of the hypothalamic-pituitary-adrenal system function were observed. Patients who switch to treatment with the Nasonex^® nasal spray after long-term therapy with systemic corticosteroids require special attention. Discontinuation of systemic corticosteroids in such patients may lead to adrenal insufficiency, the subsequent recovery from which may take up to several months. If signs of adrenal insufficiency appear, systemic corticosteroids should be resumed and other necessary measures taken.

When using intranasal corticosteroids, systemic side effects may develop, especially with long-term use in high doses. The likelihood of these effects is significantly less than with the use of oral corticosteroids. Systemic side effects may vary among individual patients and depending on the corticosteroid used. Potential systemic effects include Cushing’s syndrome, cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataracts, glaucoma, and less commonly a number of psychological or behavioral effects, including psychomotor hyperactivity, sleep disturbance, anxiety, depression, or aggression (especially in children).

During the transition from treatment with systemic corticosteroids to treatment with the Nasonex^® nasal spray, some patients may experience initial symptoms of withdrawal of systemic corticosteroids (e.g., joint and/or muscle pain, feeling of fatigue, and depression), despite a reduction in the severity of symptoms associated with nasal mucosal damage. Such patients need to be specifically convinced of the advisability of continuing treatment with the Nasonex^® nasal spray. The transition from systemic to local corticosteroids may also reveal pre-existing but masked by systemic corticosteroid therapy allergic diseases, such as allergic conjunctivitis and eczema.

Patients receiving glucocorticosteroid (GCS) therapy have potentially reduced immune reactivity and should be warned about their increased risk of infection in case of contact with individuals suffering from certain infectious diseases (e.g., chickenpox, measles), as well as about the necessity of consulting a physician if such contact occurs.

If signs of a severe bacterial infection appear (e.g., fever, persistent and sharp pain on one side of the face or toothache, swelling in the orbital or periorbital area), immediate medical consultation is required.

During the use of Nasonex^® nasal spray for 12 months, no signs of nasal mucosa atrophy occurred.

Furthermore, mometasone furoate showed a tendency to promote normalization of the histological picture in examinations of nasal mucosa biopsies.

With both systemic and local (including intranasal, inhaled, and intraocular) application of GCS, visual disturbances may occur.

If a patient experiences symptoms such as blurred vision or other visual disturbances, it is necessary to recommend that the patient consult an ophthalmologist to identify possible causes of the visual disturbances, which include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which have been observed in some cases with systemic and local GCS use.

The efficacy and safety of mometasone have not been studied in the treatment of unilateral polyps, polyps associated with cystic fibrosis, and polyps that completely obstruct the nasal cavity.

If unilateral polyps of an unusual or irregular shape are detected, especially if they are ulcerated or bleeding, additional medical examination is necessary.

Effect on the Ability to Drive Vehicles and Operate Machinery

There are no data on the effect of Nasonex^® on the ability to drive vehicles or operate moving machinery.

Overdose

With long-term use of GCS in high doses, as well as with the simultaneous use of several GCS, suppression of the hypothalamic-pituitary-adrenal (HPA) system is possible.

Due to the low systemic bioavailability of the drug (<1%, with an assay sensitivity of 0.25 pg/mL), it is unlikely that any measures other than observation with possible subsequent resumption of the drug at the recommended dose would be required in case of accidental or intentional overdose.

Drug Interactions

Combination therapy with loratadine was well tolerated by patients.

No effect of the drug on the plasma concentrations of loratadine or its primary metabolite was observed.

In these studies, mometasone furoate was not detected in plasma (with an assay sensitivity of 50 pg/mL).

Mometasone furoate is metabolized by CYP3A4.

Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, drugs containing cobicistat) may lead to increased plasma concentrations of the GCS and, possibly, an increased risk of systemic side effects of glucocorticoid therapy.

The benefits of co-administering mometasone furoate with strong CYP3A4 inhibitors and the potential risk of systemic GCS side effects should be evaluated.

In case of concomitant use, patients should be monitored for the development of systemic side effects of glucocorticoid therapy.

Storage Conditions

The drug should be stored out of the reach of children at a temperature between 2°C (35.6°F) and 25°C (77°F). Do not freeze.

Shelf Life

The shelf life is 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by 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.