Dezrinit (Spray) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Teva Czech Industries, s.r.o. (Czech Republic)

Contact Information

TEVA (Israel)

ATC Code

R01AD09 (Mometasone)

Active Substance

Mometasone (Rec.INN registered by WHO)

Dosage Form

Dezrinit

Dosed nasal spray 50 mcg/1 dose: bottle 60 doses 1 pc.; 140 doses 1, 2, or 3 pcs. with dosing device

Dosage Form, Packaging, and Composition

Dosed nasal spray as a milky-white suspension without agglomerates.

Excipients: Avicel RC-591 [microcrystalline cellulose, sodium carboxymethylcellulose] – 2 mg, glycerol – 2.1 mg, benzalkonium chloride solution (500 g/l) – 40 mcg, polysorbate 80 – 10 mcg, citric acid monohydrate – 200 mcg, sodium citrate dihydrate – 280 mcg, purified water – sufficient quantity up to 100 mg.

10 g (60 doses) – polyethylene bottles (1) with a dosing device – cardboard packs^×.
18 g (140 doses) – polyethylene bottles (1) with a dosing device – cardboard packs^×.
18 g (140 doses) – polyethylene bottles (2) with a dosing device – cardboard packs^×.
18 g (140 doses) – polyethylene bottles (3) with a dosing device – cardboard packs^×.

^× protective stickers may additionally be applied.

Clinical-Pharmacological Group

Topical corticosteroids

Pharmacotherapeutic Group

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

Pharmacological Action

Synthetic topical glucocorticosteroid. Mometasone has anti-inflammatory and anti-allergic effects. The local anti-inflammatory effect of the drug manifests when used in doses that do not cause systemic effects.

It inhibits the release of inflammatory mediators. Increases the production of lipomodulin, which is a phospholipase A inhibitor, leading to a reduction in the release of arachidonic acid and, consequently, inhibition of the synthesis of arachidonic acid metabolites – cyclic endoperoxides, prostaglandins. Prevents marginal neutrophil accumulation, which reduces inflammatory exudate and lymphokine production, inhibits macrophage migration, and leads to a reduction in infiltration and granulation processes.

It reduces inflammation by decreasing the formation of chemotactic substances (effect on late-phase allergic reactions), inhibits the development of an immediate allergic reaction (by inhibiting the formation of arachidonic acid metabolites and reducing the release of inflammatory mediators from mast cells).

In studies with antigen challenge tests applied to the nasal mucosa, a high anti-inflammatory activity of the drug was demonstrated, both in the early and late stages of the allergic reaction. Compared to placebo, a reduction in histamine levels and eosinophil activity was established, as well as a decrease (compared to baseline) in the number of eosinophils, neutrophils, and epithelial cell proteins.

Pharmacokinetics

With intranasal use, the systemic bioavailability of mometasone furoate is <1% (with an assay sensitivity of 0.25 pg/ml). Mometasone is very poorly absorbed from the gastrointestinal tract, and the small amount of active substance that may enter the gastrointestinal tract during nasal spraying undergoes active first-pass metabolism before excretion in urine or bile.

Indications

• Seasonal and perennial allergic rhinitis in adults, adolescents, and children aged 2 years and older;
• Acute sinusitis or exacerbation of chronic sinusitis in adults (including the elderly) and adolescents from 12 years – as an adjunctive 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 (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 over 18 years.

ICD codes

Dosage Regimen

The drug is used intranasally.

Inhalation of the suspension contained in the bottle is carried out using a special dosing device on the bottle. Before the first use of Dezrinit nasal spray, it is necessary to “calibrate” it.

Do not puncture the nasal applicator (spray tip).

To perform “calibration”, press the dosing nozzle 10 times or until a uniform spray appears, indicating the drug is ready for use. Tilt your head and spray the medication into each nostril according to the recommended dosing regimen.

If the medication has not been used for 14 days or longer, press the dosing device 2 times or until a uniform spray appears. Tilt your head and spray the medication into each nostril according to the recommended dosing regimen.

Cleaning the dosing device

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

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

Dry the cap and tip 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, perform a repeated “calibration” by pressing the dosing device 2 times.

Shake the bottle vigorously before each use.

Seasonal and perennial allergic rhinitis

Adults (including the elderly) and adolescents aged 12 years and older

The recommended prophylactic and therapeutic dose of the drug is 2 inhalations (50 mcg 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 inhalation into each nostril once a day (total daily dose – 100 mcg).

If symptom reduction is not achieved using the drug at the recommended therapeutic dose, the daily dose can be increased to 4 inhalations into each nostril once a day (total daily dose – 400 mcg).

After symptom reduction, a dose reduction is recommended.

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

Children aged 2-11 years

The recommended therapeutic dose is 1 inhalation (50 mcg) into each nostril once a day (total daily dose – 100 mcg). For use in young children, adult assistance is required.

Adjunctive treatment of acute sinusitis or exacerbation of chronic sinusitis

Adults (including the elderly) and adolescents aged 12 years and older

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

If symptom reduction is not achieved using the drug at the recommended therapeutic dose, the daily dose of the drug can be increased to 4 inhalations into each nostril twice a day; total daily dose – 800 mcg. After symptom reduction, a dose reduction is recommended.

Treatment of acute rhinosinusitis without signs of severe bacterial infection

The recommended dose for adults and adolescents is 2 inhalations of 50 mcg into each nostril twice a day (total daily dose 400 mcg).

If symptoms worsen during treatment, specialist consultation is necessary.

Treatment of nasal polyposis

Adults (including the elderly) from 18 years

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

After symptom reduction, a dose reduction to 2 inhalations (50 mcg each) into each nostril once a day (total daily dose – 200 mcg) is recommended.

Adverse Reactions

Adverse events associated with the use of the drug (≥1%), identified during clinical trials 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 below. 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 frequency was somewhat higher than with placebo (5%), but equal to or less than with other intranasal corticosteroids used as active controls (for some of them, the frequency of nosebleeds was up to 15%). The frequency of all other adverse events was comparable to the frequency with placebo.

The overall frequency of adverse events in patients treated for nasal polyposis was comparable to the frequency in patients with allergic rhinitis.

The overall frequency of adverse events in patients treated for acute rhinosinusitis was comparable to the frequency in patients with allergic rhinitis and with placebo.

When using intranasal corticosteroids, systemic side effects may develop, especially with long-term use of intranasal corticosteroids in high doses.

The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100, <1/10), rare (≥1/1000, <1/100).

For adverse reactions from the post-registration surveillance period, the frequency is not established (cannot be estimated from the available data).

Infections and infestations common – pharyngitis, upper respiratory tract infections*.

Immune system disorders frequency not established – hypersensitivity reactions, including anaphylactic reactions, angioedema, bronchospasm, dyspnea.

Nervous system disorders common – headache.

Eye disorders rare – blurred vision; frequency not established – increased intraocular pressure, glaucoma, cataract.

Respiratory, thoracic and mediastinal disorders very common – epistaxis**; common – nosebleeds (i.e., obvious bleeding, as well as discharge of blood-stained mucus or blood clots), burning sensation in the nose, irritation of the nasal mucosa, ulceration of the nasal mucosa; frequency not established – nasal septum perforation.

Gastrointestinal disorders common – pharyngeal irritation (sensation of pharyngeal mucosal irritation)**.

General disorders and administration site conditions frequency not established – taste and smell disorders.

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

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

Children

Respiratory, thoracic and mediastinal disorders epistaxis (6%), nasal mucosal irritation (2%), sneezing (2%).

Nervous system disorders headache (3%).

The frequency of these adverse events in children was comparable to their frequency with placebo.

Contraindications

• Hypersensitivity to mometasone or any component of the drug;
• Recent surgery or nasal trauma with damage to the nasal mucosa – until the wound has healed (due to the inhibitory effect of corticosteroids on healing processes);
• Pediatric age (for seasonal and perennial allergic rhinitis – up to 2 years; for acute sinusitis or exacerbations of chronic sinusitis – up to 12 years; for nasal polyposis – up to 18 years);

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

Use in Pregnancy and Lactation

No specific studies on the safety of mometasone use during pregnancy and breastfeeding have been conducted.

As with the use of other nasal corticosteroids, Dezrinit should be prescribed during pregnancy and lactation only if the expected benefit to the mother outweighs the potential risk to the fetus and child. Newborns whose mothers used corticosteroids during pregnancy should be carefully examined to identify possible adrenal hypofunction.

Pediatric Use

The use of the drug is contraindicated in pediatric age (for seasonal and perennial allergic rhinitis – up to 2 years; for acute sinusitis or exacerbations of chronic sinusitis – up to 12 years; for nasal polyposis – up to 18 years).

Special Precautions

As with any treatment, patients using Mometasone in the form of a dosed nasal spray for several months or longer should periodically undergo examination by a physician for possible changes in the nasal mucosa.

Monitoring is necessary for patients receiving intranasal corticosteroids for a long time. Growth retardation may develop in children. If growth retardation is detected in children, the dose of intranasal corticosteroids should be reduced to the lowest that effectively controls symptoms. Additionally, 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 mometasone in the form of a dosed nasal spray and initiate specific treatment. Persistent irritation of the nasal and pharyngeal mucosa may also be grounds for discontinuing treatment with Dezrinit.

In placebo-controlled clinical trials in children, when Mometasone in the form of a dosed 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 mometasone nasal spray, no signs of suppression of the hypothalamic-pituitary-adrenal system function were observed.

Patients who switch to treatment with mometasone in the form of a dosed 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, cataract, glaucoma, and less commonly a range 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 mometasone in the form of a dosed nasal spray, some patients may experience initial symptoms of systemic corticosteroid withdrawal (e.g., joint and/or muscle pain, feeling of tiredness, and depression), despite a reduction in the severity of symptoms associated with nasal mucosal involvement. If these signs appear, systemic corticosteroids should be resumed and other necessary measures taken. 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 corticosteroid treatment have potentially reduced immune reactivity and should be warned about their increased risk of infection in case of contact with patients with certain infectious diseases (e.g., chickenpox, measles), and about the need for medical consultation 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.

When using mometasone in the form of a dosed nasal spray for 12 months, no signs of nasal mucosal atrophy occurred. Furthermore, mometasone furoate showed a tendency to promote normalization of the histological picture in nasal mucosal biopsies.

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 ulcerated or bleeding ones, additional medical examination is necessary.

Visual disturbances have been reported with systemic and topical corticosteroid use. If a patient experiences symptoms such as blurred vision or other visual impairments, the possibility of referring the patient to an ophthalmologist for evaluation of potential causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, should be considered.

Effect on the Ability to Drive Vehicles and Mechanisms

There are no data on the effect of the Dezrinit drug on the ability to drive vehicles or operate moving mechanisms.

Overdose

With long-term use of glucocorticosteroids in high doses or with the simultaneous use of several glucocorticosteroids, suppression of the hypothalamic-pituitary-adrenal system is possible.

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

Drug Interactions

Concomitant use of mometasone with loratadine did not lead to changes in the plasma concentrations of loratadine or its main metabolite, while the presence of mometasone in plasma was not detected even at a minimal concentration. In these studies, mometasone furoate was not detected in plasma (with an assay sensitivity of 50 pg/ml).

When used concomitantly with CYP3A inhibitors, including cobicistat-containing drugs, the risk of systemic side effects increases. Their concomitant use should be avoided, except in cases where the potential benefit to the patient outweighs the possible risk of systemic corticosteroid side effects. In case of co-administration, the development of systemic corticosteroid side effects in patients should be monitored.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F); do not freeze.

Shelf Life

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

The shelf life of the opened bottle is 2 months.

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.