Sanomen

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SANO MEN (CANOMEN)

Composition:

Active substance: 1 spray dose contains 50 mcg of mometasone furoate (as mometasone furoate monohydrate);

Excipients: microcrystalline cellulose and sodium carmellose (Avicel RC-591), glycerin, citric acid monohydrate, sodium citrate dihydrate, polysorbate 80, benzalkonium chloride, water for injections.

Pharmaceutical form. Metered nasal spray, suspension.

Main physicochemical properties: white homogeneous suspension.

Pharmacotherapeutic group. Anti-inflammatory and other locally acting drugs in nasal diseases. Corticosteroids. Mometasone. ATC code R01AD09.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory activity effective 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 release of leukotrienes from leukocytes of patients suffering from allergic diseases. In cell culture, mometasone furoate demonstrated high activity in suppressing the synthesis and release of IL-1, IL-5, IL-6, and TNFα; it is also a potent inhibitor of leukotriene production. Furthermore, it is a very potent inhibitor of Th2 cytokine production, IL-4 and IL-5, from human CD4+ T-cells.

High anti-inflammatory activity of mometasone furoate has been demonstrated in both the early and late phases of the allergic reaction. This has been 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.

In 28% of patients with seasonal allergic rhinitis, mometasone furoate demonstrated a clinically significant onset of action within 12 hours after the first dose. On average (50%), symptom relief occurred within 35.9 hours.

Children

During a one-year placebo-controlled clinical study in which children (n = 49/group) received mometasone furoate at a dose of 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 mometasone furoate at doses of 50, 100, or 200 mcg/day intranasally 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.

The European Medicines Agency has waived the requirement to submit results of studies on the use of mometasone furoate in all pediatric subgroups for the treatment of seasonal or perennial allergic rhinitis.

Pharmacokinetics

Absorption

The 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).

Distribution

Mometasone is very poorly absorbed via the nasal route.

Metabolism

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

Excretion

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

Clinical characteristics.

Indications.

Treatment of symptoms of seasonal or perennial allergic rhinitis in adults and children aged 3 years and older. Prophylactic treatment of moderate to severe allergic rhinitis symptoms is recommended to begin several days before the anticipated start of pollen season.

As an adjunctive therapeutic agent in antibiotic treatment of acute episodes of sinusitis in adults (including elderly) 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.

The drug should not be used in the presence of untreated localized infections involving the nasal mucosa, such as herpes simplex.

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

Interaction with other medicinal products and other forms of interaction.

Sanomen has been used concomitantly with loratadine, with no effect observed on plasma concentrations of loratadine or its main metabolite, and mometasone furoate was not detected in plasma even at minimal concentrations. Patients tolerated combination therapy well.

Concomitant therapy with CYP3A inhibitors, including drugs 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 adverse effects; in such cases, patients should be monitored for the occurrence of systemic corticosteroid adverse reactions.

Special precautions for use.

Administration of the drug to younger children should be carried out under adult supervision.

The drug should not be used in the presence of untreated local 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 sustained nasal trauma until healing has occurred.

Sanomene nasal spray should be used with caution in patients with open or closed forms of respiratory tuberculosis, untreated fungal or bacterial infections, systemic viral infections, or herpes simplex infection involving the eyes.

After 12 months of treatment with mometasone furoate, no signs of nasal mucosal atrophy were observed in patients; furthermore, mometasone furoate contributed to normalization of the histological picture of the nasal mucosa.

Nevertheless, patients who have been receiving mometasone furoate for several months or longer should be periodically examined for possible changes in the nasal mucosa. If a localized fungal infection of the nose or throat develops, therapy with mometasone furoate should be discontinued or appropriate treatment initiated. Prolonged irritation of the nasal and pharyngeal mucosa may also be an indication for discontinuation of treatment.

Mometasone furoate is not recommended in cases of nasal septum perforation.

During clinical studies, a higher incidence of epistaxis was observed compared to placebo. These episodes of epistaxis were self-limiting and mild in severity.

Although the drug controls nasal symptoms in most patients, concomitant use of appropriate additional therapy may provide further relief of other symptoms, particularly ocular symptoms.

However, caution should be exercised when treating patients who are being transferred from long-term systemic corticosteroid therapy to Sanomene.

Discontinuation of systemic corticosteroids in such patients may result in adrenal insufficiency for several months until recovery of the hypothalamic-pituitary-adrenal (HPA) axis function.

If these patients develop symptoms of adrenal insufficiency or withdrawal symptoms (e.g., joint and/or muscle pain, fatigue, and depression), despite the absence of nasal symptoms, systemic corticosteroid therapy should be reinstated and an alternative treatment regimen considered. The change in therapy may also unmask allergic conditions such as allergic conjunctivitis or eczema, previously suppressed by systemic corticosteroid therapy.

During transition from systemic corticosteroid therapy to treatment with Sanomene nasal spray, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscle pain, fatigue, and depression). Such patients should be specifically reassured regarding the necessity of continuing treatment with Sanomene.

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

Unilateral polyps that are atypical should be further evaluated, especially if ulcers or bleeding are present. Patients receiving corticosteroids may have potentially reduced immune responsiveness and should be warned about the increased risk of infectious diseases (e.g., varicella, measles) and advised to consult a physician if exposed to such infections.

Very rare cases of nasal septum perforation or increased intraocular pressure have been reported after administration of intranasal corticosteroids.

Systemic effects of intranasal corticosteroids may occur when the drug is used predominantly at high doses over a prolonged period. These effects are much less likely than with oral corticosteroids and may vary among individual patients and with 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 including psychomotor hyperactivity, sleep disturbances, restlessness, depression, or aggression (particularly in children).

Sanomene nasal spray contains 20 mcg/dose of benzalkonium chloride, which may cause irritation of the nasal mucosa. With prolonged use, the preservative benzalkonium chloride may cause nasal mucosal edema. In case of such a reaction (persistent nasal congestion), preservative-free nasal formulations should be preferred if possible. If such products are unavailable, switching to another pharmaceutical form of the drug should be considered.

Treatment with doses exceeding the recommended ones may lead to clinically significant adrenal suppression. When the drug is used at doses exceeding the recommended, additional systemic corticosteroid therapy should be considered during periods of stress or planned surgical intervention.

In children receiving long-term treatment with intranasal corticosteroids, regular monitoring of growth is recommended. If a child's growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of intranasal corticosteroids, if possible, to the lowest effective dose controlling disease symptoms. In addition, consultation with a pediatrician is recommended.

Visual disturbances may occur with systemic and topical corticosteroid use. If a patient develops symptoms such as blurred vision or other visual disturbances, they should be advised to consult an ophthalmologist to evaluate possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSC), reported after systemic and topical corticosteroid use.

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

The safety and efficacy of the drug in treating rhinosinusitis symptoms in children under 12 years of age have not been studied.

Precautions and preventive measures

Local nasal adverse reactions

Epistaxis

Epistaxis occurred more frequently in patients with allergic rhinitis and in patients with chronic rhinosinusitis with nasal polyps receiving mometasone furoate than in those receiving placebo (see section "Adverse reactions").

Candida infection

Localized infections of the nose and throat caused by Candida albicans have occurred following intranasal administration of mometasone furoate. If such an infection develops, administration of mometasone furoate should be discontinued and appropriate local or systemic therapy initiated if necessary.

Nasal septum perforation

Cases of nasal septum perforation have been observed in patients after intranasal administration of corticosteroids, including mometasone furoate. As with any prolonged local treatment of the nasal cavity, patients receiving mometasone furoate for several months or longer should be periodically examined for possible changes in the nasal mucosa.

Impaired wound healing

Due to the inhibitory effect of corticosteroids on wound healing, intranasal corticosteroids should not be administered to patients who have recently experienced nasal septum ulcers, nasal surgery, or nasal trauma until complete healing has occurred.

Hypercorticism and adrenal suppression

Hypercorticism and adrenal suppression may occur when intranasal corticosteroids, including mometasone furoate, are used at doses higher than recommended (see section "Dosage and administration") or in patients at risk of developing such effects. If such changes occur, the dose of mometasone furoate should be gradually discontinued according to established procedures for discontinuation of oral corticosteroid therapy.

Effect on growth

Corticosteroids, including mometasone furoate, may cause reduced growth velocity when administered to children. Pediatric patients receiving mometasone furoate should be monitored regularly for growth. To minimize systemic effects of intranasal corticosteroids, including mometasone furoate, the dose for each patient should be titrated to the lowest effective dose controlling their symptoms (see section "Use in specific populations").

Geriatric use

Overall, 280 patients aged 64 years and older with allergic rhinitis or chronic rhinosinusitis with nasal polyps (age range 64 to 86 years) received mometasone furoate for 3 or 4 months, respectively. No differences in safety and/or efficacy were observed in elderly patients compared to younger adult patients.

Use during pregnancy or breastfeeding.

Mometasone is minimally systemically absorbed after intranasal administration, and it is not expected that administration of the drug by the mother will affect the fetus. Available observational data on the use of mometasone furoate in pregnant women are insufficient to determine the associated risk of major congenital malformations, miscarriage, or other adverse outcomes for the mother or fetus. In reproductive animal studies in pregnant mice, rats, or rabbits (subcutaneous, subcutaneous/dermal topical/oral, and dermal topical/oral, respectively), mometasone furoate caused increased fetal malformations and reduced fetal survival and growth after administration of doses resulting in exposures approximately 1/3 to 8 times the maximum recommended human dose based on mcg/m² or AUC (see Results). However, experience with oral corticosteroids indicates that rodents are more susceptible to teratogenic effects of corticosteroids than humans.

The background risk of major congenital malformations and miscarriage in the indicated population is unknown. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the general US population, the estimated risk of major congenital malformations and miscarriage during clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Results

Animal study results

In an embryo-fetal development study in pregnant mice receiving the drug during the period of organogenesis, mometasone furoate caused cleft palate at a dose lower than the maximum recommended intranasal daily dose (MRDID) (based on mcg/m² with maternal subcutaneous doses of 60 mcg/kg and above) and reduced fetal survival at approximately 2 times the MRDID (based on mcg/m² with maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed at a dose causing exposure less than the MRDID (based on mcg/m² with maternal topical dermal doses of 20 mcg/kg and above).

Lactation

There are no available data on the presence of mometasone furoate in human milk, its effects on the breastfed child, or its effects on milk production. However, mometasone furoate is minimally systemically absorbed by the mother after intranasal administration, and breastfeeding is not expected to result in significant exposure of the infant to mometasone. The benefits of breastfeeding for the child's development and health should be weighed against the mother's clinical need for mometasone and any potential adverse effects of mometasone furoate on the breastfed infant or the underlying maternal condition.

Ability to affect reaction rate when driving or operating machinery.

Unknown.

Method of Administration and Dosage

SanoMen is intended for nasal use only.

Before initiating treatment, the preparation should be primed. Priming is performed by approximately 10 actuations of the dosing device, which establishes a consistent delivery of the active substance, ensuring that each spray releases approximately 100 mg of suspension containing 50 µg of mometasone (1 dose).

If the nasal spray has not been used for 14 days or longer, re-priming is required before the next use by spraying twice until a full spray is observed.

Treatment of seasonal or perennial allergic rhinitis. The recommended prophylactic and therapeutic dose for adults (including elderly) and children aged 12 years and older is 2 sprays (50 µg each) in each nostril once daily (total daily dose – 200 µg). After achieving the therapeutic effect, the dose should be reduced to 1 spray in each nostril once daily (total daily dose – 100 µg) 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 in each nostril once daily (total daily dose – 400 µg). After symptom relief is achieved, dose reduction is recommended.

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

Treatment with SanoMen nasal spray should be initiated several days before the anticipated start of pollen season (flowering) in patients with a history of moderate to severe seasonal allergic rhinitis.

For children aged 3–11 years, the recommended therapeutic dose is 1 spray (50 µg) in each nostril once daily (total daily dose – 100 µg).

Adjunctive treatment of acute sinusitis episodes. The recommended therapeutic dose for adults (including elderly) and children aged 12 years and older is 2 sprays (50 µg each) in each nostril twice daily (total daily dose – 400 µg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to 4 sprays in each nostril twice daily (total daily dose – 800 µg). Dose reduction is recommended once symptom relief is achieved.

Acute rhinosinusitis. The recommended therapeutic dose for adults and children aged 12 years and older is 2 sprays (50 µg each) in each nostril twice daily (total daily dose – 400 µg).

Nasal polyps. For patients aged 18 years and older (including elderly), the recommended initial dose is 2 sprays (50 µg each) in each nostril once daily (total daily dose – 200 µg). If symptom improvement is not achieved after 5–6 weeks of treatment, the daily dose may be increased to 2 sprays in each nostril twice daily (total daily dose – 400 µg). The dose should be titrated to the lowest effective dose that maintains symptom control. If no symptom improvement is observed after 5–6 weeks of twice-daily dosing, alternative treatment options should be considered.

The clinical studies evaluating the efficacy and safety of mometasone furoate nasal spray for nasal polyps lasted 4 months.

Pediatric Population.

The safety and efficacy of mometasone furoate for the prevention of nasal symptoms of seasonal allergic rhinitis have been established in pediatric patients aged 12 years and older (see sections "Adverse Reactions" and "Clinical Studies"). The use of mometasone furoate for this indication is supported by evidence from controlled trials involving adults and children aged 12 years and older (see section "Clinical Studies").

The safety and efficacy of mometasone furoate for the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients under 18 years of age have not been established. Efficacy was not demonstrated in a single 4-month study evaluating the safety and efficacy of mometasone furoate in children aged 6 to 17 years with chronic rhinosinusitis and nasal polyps. The primary objective of the study was to assess safety; efficacy parameters were collected as secondary endpoints. A total of 127 patients with chronic rhinosinusitis and nasal polyps were randomized to receive placebo or mometasone furoate 100 µg once or twice daily (patients aged 6–11 years) or 200 µg once or twice daily (patients aged 12–17 years). The results of this study did not confirm the efficacy of mometasone furoate in treating chronic rhinosinusitis with nasal polyps in children. Adverse reactions reported in this study were similar to those reported in patients aged 18 years and older with chronic rhinosinusitis and nasal polyps.

Effect on Growth.

Controlled clinical studies have shown that nasal corticosteroids may cause a reduction in growth velocity in children. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, indicating that growth velocity is a more sensitive indicator of systemic corticosteroid effects in pediatric patients than some of the commonly used HPA axis function tests. The long-term consequences of this reduced growth velocity associated with nasal corticosteroids, including the impact on final adult height, are unknown. The potential for "catch-up" growth after discontinuation of nasal corticosteroids has not been adequately studied. Growth in children receiving nasal corticosteroids, including mometasone furoate, should be monitored regularly (e.g., using stadiometry). The potential impact of long-term treatment on growth should be weighed against the clinical benefits obtained and the availability of safe and effective non-corticosteroid alternative treatments. To minimize systemic effects of nasal corticosteroids, including mometasone furoate, the lowest effective dose should be used for each patient.

Overdose.

Since the systemic bioavailability of mometasone furoate is < 1%, it is unlikely that any measures other than observation and subsequent administration of the drug at the recommended dose will be required in case of overdose.

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

Adverse Reactions

The adverse reactions listed below are associated with the use of mometasone furoate (≥ 1%) and were observed during clinical studies in patients with allergic rhinitis or nasal polyposis, as well as during post-marketing use.

Adverse reactions are classified by system organ class and frequency of occurrence. Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and frequency not known (cannot be estimated from available data).

Respiratory system: very common – epistaxis*; common – epistaxis, nasal mucosal irritation, burning sensation in the nasal mucosa, nasal mucosal ulcers; frequency not known – nasal septum perforation.

General disorders and administration site conditions: common – headache; rare – hypersensitivity reactions; very rare – anaphylaxis, angioedema, disturbances of smell and taste.

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

Immune system disorders: frequency not known – hypersensitivity, including anaphylactic reactions, angioedema, bronchospasm and dyspnea; immunosuppression and increased risk of infections.

Nervous system disorders: common – headache.

Gastrointestinal disorders: common – throat irritation*, abdominal pain, diarrhea, nausea; frequency not known – taste and smell disturbances.

Eye disorders: frequency not known – glaucoma, increased intraocular pressure, cataract, central serous chorioretinopathy, blurred vision.

Blood and lymphatic system disorders: epistaxis, ulcers, Candida albicans infection, impaired wound healing.

Renal and adrenal disorders: hypercorticism and adrenal suppression, including growth suppression.

* Observed with twice-daily administration for treatment of nasal polyposis; commonly observed in rhinosinusitis treatment.
** Observed uncommonly with twice-daily administration for treatment of nasal polyposis.

Description of selected adverse reactions

Nasal bleeding was generally mild, self-limiting, and occurred slightly more frequently than with placebo (5%), but no more frequently than with other investigational intranasal corticosteroids used as active controls (up to 15%). The incidence of all other adverse reactions was comparable to that observed with placebo.

In patients receiving treatment for nasal polyposis, 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.

Children

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

"From clinical trials"

Because clinical trials are conducted under varying conditions, the frequency of adverse reactions observed in clinical trials of one drug cannot be directly compared with those of another, and may not reflect the frequency observed in clinical practice.

Allergic Rhinitis

Adults and children aged 12 years and older

In controlled U.S. and international clinical trials, a total of 3,210 adults and children aged 12 years and older with allergic rhinitis received intranasal mometasone furoate at doses ranging from 50 to 800 mcg/day. The majority of patients (n=2,103) received 200 mcg/day. A total of 350 adults and children aged 12 years and older were treated for one year or longer. Adverse reactions did not differ significantly by age, gender, or race. Four percent or fewer patients discontinued treatment due to adverse effects in clinical trials, and discontinuation rates were similar between the drug and active comparators.

All adverse reactions (regardless of causal relationship to treatment) reported in ≥5% of adults and children aged 12 years and older receiving intranasal mometasone furoate at 200 mcg/day, compared to placebo, and occurring more frequently with mometasone furoate than with placebo. Adults and children aged 12 years and older – adverse reactions from controlled clinical trials in seasonal and perennial allergic rhinitis (percentage of patients reporting the event).

Other adverse reactions occurring in less than 5% but in ≥2% of adults and children (aged 12 years and older) receiving intranasal mometasone furoate 200 mcg/day (regardless of causal relationship to treatment), and more frequently than in the placebo group, included: arthralgia, asthma, bronchitis, chest pain, conjunctivitis, diarrhea, dyspepsia, ear pain, influenza-like symptoms, myalgia, nausea, and rhinitis.

Chronic Rhinosinusitis with Nasal Polyps

Adults aged 18 years and older

In controlled clinical studies, the types of adverse reactions observed in patients with chronic rhinosinusitis with nasal polyps were similar to those seen in patients with allergic rhinitis. A total of 594 adult patients (aged 18 to 86 years) received intranasal mometasone furoate at doses of 200 mcg once or twice daily for 4 months for treatment of chronic rhinosinusitis with nasal polyps. The overall incidence of adverse reactions in patients receiving intranasal mometasone furoate was comparable to that in placebo recipients, except for epistaxis, which occurred in 9% with 200 mcg once daily, 13% with 200 mcg twice daily, and 5% with placebo.

Table 1

Adults and children aged 12 years and older – adverse reactions observed during clinical trials in patients with seasonal and perennial allergic rhinitis.

Headache 26 22

Viral infections 14 11

Pharyngitis 12 10

Nosebleed 11 6

Cough 7 6

Upper respiratory tract infections 6 2

Dysmenorrhea 5 3

Muscle pain 5 3

Sinusitis 5 3

Shelf life. 2 years. After first opening of the container – 2 months.

Storage conditions. Store at a temperature not exceeding 25 ºC. Do not freeze. Keep out of reach of children.

Packaging. 1 container containing 60, 120 or 140 doses; 1 container per box.

Prescription status. Prescription only.

Manufacturer.

Lek Pharmaceuticals d.d.

Manufacturer's address and place of business.

Verovskova 57, Ljubljana 1526, Slovenia /Verovskova 57, Ljubljana, 1526, Slovenia.