Nosefrine, spray 50 mcg/dose 18 g 120 doses

Pharmacotherapeutic group
Glucocorticosteroid for topical use.

TAC code
R01AD09

Pharmacological properties

Pharmacodynamics

Mometazon is a synthetic GCS for topical use. It has anti-inflammatory and anti-allergic effects when used in doses at which there are no systemic effects.

Inhibits the release of inflammatory mediators. It increases lipomodulin production, which is an inhibitor of phospholipase A, resulting in decreased release of arachidonic acid and, accordingly, inhibiting the synthesis of products of arachidonic acid metabolism – cyclic endoperoxides, PG. It prevents marginal accumulation of neutrophils, which reduces inflammatory exudate and lymphokine production, inhibits macrophage migration, leads to a decrease in infiltration and granulation processes.

It reduces inflammation due to decrease of chemotaxis substance formation (effect on delayed allergy reactions), inhibits development of immediate allergic reaction (caused by inhibition of arachidonic acid metabolites production and decrease of inflammatory mediators release from mast cells).

In studies with provocation tests with application of antigens on nasal mucosa high anti-inflammatory activity of mometasone was demonstrated both in early and in late stage of allergic reaction. This was confirmed by a decrease (compared to placebo) in the level 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

When administered intranasally, the systemic bioavailability of mometasone is less than 1% (with a sensitivity of 0.25 pg/mL determination method). The mometasone suspension is very poorly absorbed in the gastrointestinal tract, and the small amount of mometasone suspension that may enter the gastrointestinal tract after nasal inhalation is actively metabolized before excretion by the kidneys or with bile.

Indications

Seasonal or year-round allergic rhinitis in adults, adolescents and children over 2 years of age;
acute sinusitis or exacerbation of chronic sinusitis in adults (including the elderly) and adolescents over 12 years of age as part of complex therapy;
acute rhinosinusitis with mild to moderate symptoms without signs of severe bacterial infection in patients aged 12 years and older;
preventive treatment of moderate and severe seasonal allergic rhinitis in adults and adolescents from 12 years of age (recommended 2–4 weeks before the expected start of the dusting season);
nasal polyposis, accompanied by impaired nasal breathing and sense of smell, in adults (over 18 years of age).

Pharmacological effect

Pharmacotherapeutic group
Glucocorticosteroid for local use.

ATX code
R01AD09

Pharmacological properties

Pharmacodynamics

Mometasone is a synthetic corticosteroid for topical use. It has anti-inflammatory and antiallergic effects when used in doses at which systemic effects do not occur.

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, accordingly, inhibition of the synthesis of arachidonic acid metabolic products – cyclic endoperoxides, PG. Prevents the marginal accumulation of neutrophils, which reduces inflammatory exudate and the production of lymphokines, inhibits the migration of macrophages, and leads to a decrease in the processes of infiltration and granulation.

Reduces inflammation by reducing the formation of a chemotaxis substance (impact on late allergy reactions), inhibits the development of an immediate 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 the application of antigens to the nasal mucosa, the high anti-inflammatory activity of mometasone was demonstrated in both the early and late stages of the allergic reaction. This was confirmed by a decrease (compared with placebo) in histamine levels and eosinophil activity, as well as a decrease (compared with baseline) in the number of eosinophils, neutrophils and epithelial cell adhesion proteins.

Pharmacokinetics

When administered intranasally, the systemic bioavailability of mometasone is less than 1% (with a sensitivity of the detection method of 0.25 pg/ml). The mometasone suspension is very poorly absorbed from the gastrointestinal tract, and the small amount of mometasone suspension that can enter the gastrointestinal tract after nasal inhalation undergoes active primary metabolism even before excretion by the kidneys or bile.

Special instructions

As with any long-term treatment, patients using mometasone nasal spray for several months or longer should be periodically assessed by their doctor for possible changes in the nasal mucosa. It is necessary to monitor patients receiving intranasal corticosteroids for a long time.

Possible development of growth retardation in children. If growth retardation is detected in children, it is necessary to reduce the dose of intranasal corticosteroids to the lowest that allows for effective control of symptoms. In addition, the patient should be referred to a pediatrician for consultation.

If a local fungal infection of the nose or throat develops, it may be necessary to discontinue nasal spray therapy and undergo special treatment. Irritation of the mucous membrane of the nose and pharynx that persists for a long time can also serve as a basis for stopping treatment with the drug.

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

With long-term treatment with mometasone nasal spray, no signs of suppression of HPA function were observed. Patients who switch to treatment with the drug after long-term therapy with systemic GCS require special attention. Withdrawal of systemic corticosteroids in such patients can lead to adrenal insufficiency, the subsequent recovery of 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 developing these effects is much less than with the use of oral corticosteroids. Systemic side effects may vary both in individual patients and depending on the GCS drug 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 drug, some patients may experience initial withdrawal symptoms of systemic corticosteroids (for example, joint and/or muscle pain, fatigue and depression), despite a decrease in the severity of symptoms associated with damage to the nasal mucosa. Such patients must be specifically convinced of the advisability of continuing treatment with the drug. The transition from systemic to local GCS can also reveal allergic diseases such as allergic conjunctivitis and eczema that already existed but were masked by systemic GCS therapy.

Patients undergoing treatment with corticosteroids have a potentially reduced immune reactivity and should be warned about their increased risk of infection in case of contact with patients with certain infectious diseases (for example, chickenpox, measles), as well as the need for medical advice if such contact occurs. If signs of a severe bacterial infection appear (for example, 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.

When using intranasal spray with mometasone for 12 months, there were no signs of atrophy of the nasal mucosa. In addition, mometasone furoate tended to promote normalization of the histological picture when examining biopsy specimens of the nasal mucosa.

With systemic and local (including intranasal, inhalation and intraocular) use of GCS, visual impairment may occur. If the patient has 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 visual disturbances, including cataracts, glaucoma or rare diseases, for example, central serous chorioretinopathy, which have been observed in some cases with systemic and local use of GCS.

The effectiveness and safety of mometasone have not been studied in the treatment of unilateral polyps, polyps associated with cystic fibrosis, and polyps that completely occlude the nasal cavity. If unilateral polyps of an unusual or irregular shape are detected, especially those that are ulcerated or bleeding, additional medical examination is necessary.

Impact on the ability to drive vehicles and machinery

Since visual disturbances have been reported in patients receiving this drug, patients should exercise caution before operating vehicles or machinery.

Active ingredient

Mometasone

Composition

1 dose contains:
active ingredient: mometasone furoate – 50 mcg;
excipients: microcrystalline cellulose and sodium carboxymethylcellulose – 2000 mcg, glycerol – 2100 mcg, citric acid monohydrate – 200 mcg, sodium citrate dihydrate – 280 mcg, polysorbate 80 – 10 mcg, benzalkonium chloride (50% solution) – 40 mcg, purified water – up to 0.1 g.

Pregnancy

There have been no properly designed and well-controlled studies of the drug in pregnant women.
As with the use of other nasal corticosteroids, mometasone should be used during pregnancy and breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus or newborn.
Newborns whose mothers used mometasone during pregnancy should be closely monitored for the possibility of hypoadrenal hypofunction.

Contraindications

hypersensitivity to mometasone or to any of the components included in the drug;
recent surgery or trauma to the nose with damage to the nasal mucosa – before the wound heals (due to the inhibitory effect of GCS on the healing process);
children’s age (for seasonal and year-round 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

tuberculosis infection (active or latent) of the respiratory tract;
untreated fungal, bacterial, systemic viral infection or infection caused by Herpes simplex with eye damage (as an exception, the drug can be used for these infections as directed by a doctor);
untreated local infection involving the nasal mucosa.

Side Effects

Use of the drug in clinical trials

Adverse events associated with the use of mometasone (>1%) identified during clinical trials in patients with allergic rhinitis or nasal polyposis and during post-marketing use of the drug, regardless of the indication for use, are presented in Table 1. Adverse reactions are listed in accordance with the MedDRA system-organ class classification. Within each systemic organ class, adverse reactions are classified by frequency of occurrence.

Nosebleeds, as a rule, were moderate and stopped on their own. The incidence was slightly higher than with placebo (5%), but equal to or lower than with other intranasal corticosteroids that were used as active controls (some of which had an incidence of nosebleeds of up to 15%).

The incidence of all other adverse events was comparable to that observed with placebo. The overall incidence of adverse events in patients treated for nasal polyposis was comparable to the incidence in patients with allergic rhinitis.

The overall incidence of adverse events in patients treated for acute rhinosinusitis was comparable to the incidence in patients with allergic rhinitis and placebo. When using intranasal GCS, systemic side effects may develop, especially with long-term use of intranasal GCS in high doses (see “Special Instructions”).

Table 1

The frequency of adverse reactions is established as follows: very often (≥1/10); often (≥1/100, <1/10); rare (≥1/1000, <1/100). For adverse reactions during post-registration surveillance, the frequency has not been established (cannot be determined based on available data).

System-organ class

Very often

Often

Frequency not set

Infections and infestations

Pharyngitis, upper respiratory tract infections*

Immune system disorders

Hypersensitivity reactions, including anaphylactic reactions, angioedema, bronchospasm, shortness of breath

Nervous system disorders

Headache

Visual disorders

Increased intraocular pressure, glaucoma, cataracts

Respiratory, thoracic and mediastinal disorders

Nosebleeds**

Nosebleeds (i.e. obvious bleeding as well as blood-stained mucus or blood clots), burning sensation in the nose, irritation of the nasal mucosa, ulceration of the nasal mucosa

Perforation of the nasal septum

Gastrointestinal disorders

Pharyngeal irritation (feeling of irritation of the pharyngeal mucosa)**

Disorders of taste and smell

*Revealed with a frequency of “rarely” when using the drug 2 times a day for nasal polyposis.

**Detected when using the drug 2 times a day for nasal polyposis.

Children

From the respiratory system, chest and mediastinal organs:

nosebleeds (6%), irritation of the nasal mucosa (2%), sneezing (2%).

From the nervous system: headache (3%).

The incidence of these adverse events in children was comparable to the incidence when using placebo.

Post-registration use of the drug

During post-registration use of mometasone nasal spray, additional adverse reactions were identified: blurred vision.

Interaction

Combination therapy with loratadine was well tolerated by patients. However, no effect of the drug on the concentration of loratadine or its main metabolite in the blood plasma was noted. In these studies, mometasone furoate was not detected in blood plasma (with a sensitivity of the detection method of 50 pg/ml).
Mometasone furoate is metabolized by CYP3A4. Concomitant use with strong CYP3A4 inhibitors (for example, ketoconazole, itraconazole, clarithromycin, ritonavir, medicinal products containing cobicistat) may lead to increased plasma concentrations of glucocorticosteroids and possibly an increased risk of systemic side effects of glucocorticosteroid therapy. The benefits of co-administration of mometasone furoate with strong CYP3A4 inhibitors and the potential risk of systemic side effects of glucocorticosteroids should be assessed. In the case of combined use of drugs, monitoring of patients’ condition for the development of systemic side effects of glucocorticosteroid therapy is required.

Overdose

Symptoms
Inhibition of the function of the hypothalamic-pituitary-adrenal system (may occur in the case of long-term use of GCS in high doses, as well as with the simultaneous use of several GCS).
Treatment
Due to the low systemic bioavailability of the drug (less than 1% with a sensitivity of the detection method of 0.25 pg/ml), it is unlikely that in case of accidental or intentional overdose, any measures other than observation will be required with the possible subsequent resumption of the drug at the recommended dose. If necessary, treatment is symptomatic.

Storage conditions

Store at a temperature not exceeding 25 ºС.
Keep out of the reach of children.
Do not freeze!

Shelf life

3 years.
Do not use after expiration date.

Manufacturer

Vertex, Russia