Mometasone furoate (Mometasoni furoas)
The drug interacts with intracellular glucocorticoid receptors, promoting the release of the receptor from connection with immunophilin and heat shock proteins 70 and 90. Penetration of the activated receptor into the nucleus, binding to glucocorticoid-sensitive regulatory elements of DNA - a specific effect on gene expression (activation and suppression). Interaction with other protein transcription factors, including NFκB and AP-1, which regulate the expression of many immune system proteins, resulting in suppression of the expression of genes encoding some cytokines, collagenase and stromelysins.
The anti-inflammatory effect of mometasone is due to several factors.
1. The drug induces the synthesis of lipocortin, which inhibits the activity of phospholipase A2. Inhibition of phospholipase A2-mediated hydrolysis of membrane phospholipids in damaged tissues prevents the formation of arachidonic acid. Impaired formation of arachidonic acid actually means inhibition of prostaglandin synthesis, since arachidonic acid is a substrate for further metabolism through the cyclooxygenase pathway, as well as through the lipoxygenase pathway with a corresponding inhibition of leukotriene synthesis.
2. The anti-inflammatory effect of glucocorticoids is potentiated by their ability to inhibit the expression of COX-2 genes, which also leads to a decrease in the synthesis of prostaglandins at the site of inflammation, including pro-inflammatory prostaglandins E2 and I2.
3. Mometasone furoate inhibits the expression of intercellular adhesion molecules in the endothelium of blood vessels, disrupting the penetration of neutrophils and monocytes into the site of inflammation. After the administration of glucocorticoids, an increase in the concentration of neutrophils in the blood is noted (due to their receipt from the bone marrow and due to the restriction of migration from the blood vessels). This causes a decrease in the number of neutrophils at the site of inflammation.
Mometasone furoate inhibits the transcription of genes for cytokines that stimulate the inflammatory and immune response (IL-1, IL-2, IL-6, IL-8), as well as tumor necrosis factor (and some others). Also noted is a decrease in the transcription rate and increased degradation of receptor genes for IL-1 and IL-2, inhibition of transcription of metalloproteinase genes (collagenase, elastase, etc.) involved in increasing the permeability of the vascular wall, in the processes of scarring and destruction of cartilage tissue in joint diseases.
The immunosuppressive effect is due to inhibition of transcription of DNA encoding the major histocompatibility complex, proinflammatory cytokines and inhibition of T-lymphocyte proliferation. Leads to a decrease in the number of T-lymphocytes and their influence on B-lymphocytes, inhibits the production of immunoglobulins. Reduces the formation and increases the breakdown of components of the complement system.
The antiallergic effect is associated with inhibition of the synthesis of allergy mediators, degranulation of mast cells and the release of allergy mediators, and therefore it is effective for immediate allergic reactions.
Mometasone Sandoz, 50 mcg/dose, 140 doses, metered-dose nasal spray, 18 g, 1 pc.
As with any long-term treatment, patients using Mometasone Sandoz® Nasal Spray for several months or longer should be periodically examined by a 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 Mometasone Sandoz® nasal spray therapy and undergo special treatment. Irritation of the nasal and pharyngeal mucosa that persists for a long time may also serve as a reason to discontinue treatment with mometasone.
In placebo-controlled clinical trials in children, when a nasal spray containing mometasone was used at a daily dose of 100 mcg for a year, no growth retardation was observed in children. With long-term treatment with a nasal spray containing mometasone, no signs of suppression of the function of the hypothalamic-pituitary-adrenal axis were observed.
Patients who switch to treatment with Mometasone Sandoz® nasal spray after long-term treatment 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 in individual patients and depending on the glucocorticosteroid drug used. Potential systemic effects include Cushing's syndrome, characteristic Cushingoid signs, 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 Mometasone Sandoz® nasal spray, 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 reassured of the advisability of continuing treatment with Mometasone Sandoz® nasal spray.
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 treated with glucocorticosteroids have a potentially reduced immune responsiveness and should be warned of their increased risk of infection if exposed to patients with certain infectious diseases (eg, chickenpox, measles), as well as the need for medical advice if such exposure occurs .
If signs of a significant bacterial infection appear (for example, fever, persistent or sharp pain on one side of the face or toothache, swelling in the orbital or periorbital area), immediate medical consultation is required.
When using a nasal spray containing mometasone, there are no signs of atrophy of the nasal mucosa for 12 months. In addition, mometasone furoate tends to help normalize the histological picture when examining biopsies of the nasal mucosa.
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.
The development of visual disturbances has been reported with the use of both systemic and local corticosteroids. If the patient experiences blurred vision or other visual disturbances, the patient should be referred to an ophthalmologist to determine possible causes, which may include the development of cataracts, glaucoma, or rarer diseases (eg, central serous chorioretinopathy) that have been reported with the use of systemic and topical corticosteroids .
Special precautions when disposing of unused medicinal product
The bottle must be discarded after the specified number of uses or 2 months from the date of first use.
Impact on the ability to drive vehicles and operate machinery
No studies have been conducted to study the effect of the drug on the ability to drive vehicles and operate machinery.
Instructions
The list of adverse events below is based on data from clinical studies in seasonal and perennial allergic rhinitis, as well as data from post-registration use of individual components of the drug.
Seasonal allergic rhinitis
In a clinical study conducted in 560 patients aged 12 to 65 years with seasonal allergic rhinitis, 282 patients received azelastine hydrochloride + mometasone furoate nasal spray for an average of 14.94 days.
Overall, the safety profile of azelastine hydrochloride + mometasone furoate nasal spray was comparable to the profiles of the individual components used as monotherapy in the study, and was also consistent with the available published data on monotherapy with the individual components of the combination. A total of 18 adverse events associated with the use of azelastine hydrochloride + mometasone furoate nasal spray were reported in 11 of 282 patients. The most common adverse events recorded in the study were headache (5 cases) and dysgeusia (5 cases). Other adverse events were drowsiness (3 cases), lethargy (2 cases), nausea (1 case), dyspepsia (1 case) and sneezing (1 case). Most of these adverse events were mild in severity, and no serious adverse events were reported during the study.
In another clinical study conducted on 220 patients with seasonal allergic rhinitis, 55 patients received azelastine hydrochloride + mometasone furoate nasal metered spray, 1 spray in each nostril twice a day in the morning and evening, 55 patients received azelastine hydrochloride + nasal metered spray. mometasone furoate 2 injections into each nostril once a day, 55 patients dosed spray mometasone furoate and 55 patients dosed spray azelastine hydrochloride. The duration of treatment with these drugs was 14 days. During the entire study period, adverse events were identified in 51 participants (23%). During the study, the following adverse events were noted: drowsiness (0.9%), bitter taste in the mouth (3.6%), headache (2.7%), nosebleeds (1.8%), burning sensation in the nose after application (9.5%), sneezing after use (4.1%), increased appetite (0.5%), dry nose (4.1%), abnormalities in tests (0.9%), swelling of the mucous membrane nose (0.5%), nasal congestion (0.5%), rhinorrhea (0.9%), sinus arrhythmia (0.9%), redness of the hands (red spots) (0.5%), dry eyes ( 0.5%), hemorrhagic exanthema (0.5%), abnormal urinalysis (0.5%), swelling of the eyelids (0.5%), burning sensation in the eye area (0.5%) and loss of smell ( 0.5%). Mild adverse events accounted for 74.5%, and moderate adverse events accounted for 25.5% of the total number of adverse events.
Year-round allergic rhinitis
In a clinical study conducted in 150 patients with perennial allergic rhinitis, 75 patients received azelastine hydrochloride nasal metered spray + mometasone furoate, and 75 patients received combination therapy with azelastine hydrochloride nasal metered spray and mometasone furoate nasal metered spray from different devices. The duration of treatment with these drugs was 28 days. During the entire study period, 51 adverse events were reported in 23 of 150 patients (15.33%). The most common adverse events reported in the study were headache (10 cases), nosebleeds (6 cases), excessive sneezing (5 cases), and mucosal burning sensation (4 cases). Most adverse events were mild or moderate in severity, and no serious adverse events were reported during the study. A comparative analysis of the observed adverse events in the groups revealed no differences between the groups. During the study, 94.74% (18/19) of mild adverse events and 5.26% (1/19) of moderate adverse events were observed in the group of patients receiving azelastine hydrochloride + mometasone furoate nasal dosed spray.
The following are adverse drug events reported with the use of individual components of the fixed-dose combination.
According to the World Health Organization (WHO), adverse events are classified based on systemic organ classes according to the frequency of their development as follows:
very often - ≥ 1/10; often - from ≥ 1/100 to infrequently - from ≥ 1/1000 to rarely - from ≥ 1/10000 to very rarely - frequency unknown - it is not possible to determine the frequency of occurrence based on available data.
Azelastine hydrochloride
Often:
after use, a substance-specific bitter taste may be felt (often due to improper use, namely by excessively tilting the head back during use), which in rare cases can cause nausea.
Infrequently:
Mild, transient irritation of the inflamed nasal mucosa may occur, with symptoms such as burning, itching, sneezing and nosebleeds.
Very rarely:
Hypersensitivity reactions (such as rash, itching, urticaria), anaphylactoid reactions, dizziness, fatigue, drowsiness, weakness (may be due to the disease itself) have been reported.
Mometasone furoate
Adverse events associated with the use of the drug (≥1%) identified during clinical trials in patients with allergic rhinitis or nasal polyposis, and during post-registration use of the drug, regardless of the indication for use, are presented below. The overall incidence of adverse events in patients treated for acute rhinosinusitis was comparable to the incidence in patients with allergic rhinitis and placebo.
Nosebleeds, as a rule, were moderate and stopped on their own, the frequency of their occurrence was slightly higher than when using placebo (5%), but equal or less than when prescribing other intranasal corticosteroids, which were used as an active control (in some of In them, the incidence of nosebleeds was up to 15%). The incidence of all other adverse events was comparable to that observed with placebo.
Infectious and parasitic diseases:
often - pharyngitis, upper respiratory tract infections*
Immune system disorders:
frequency not established - hypersensitivity reactions, including anaphylactic reactions, angioedema, bronchospasm, shortness of breath.
Nervous system disorders:
often - headache.
Visual disorders:
frequency not established - increased intraocular pressure, glaucoma, cataracts, blurred vision (blurred vision).
Disorders of the respiratory system, chest and mediastinal organs:
very often - nosebleeds**; often - nosebleeds (i.e. obvious bleeding, as well as the release 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 - perforation of the nasal septum.
Gastrointestinal disorders:
often - pharyngeal irritation (feeling of irritation of the pharyngeal mucosa)**; frequency not established - disturbance of taste and smell.
* — detected 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.
When using intranasal corticosteroids, systemic side effects may develop, especially with long-term use of intranasal corticosteroids in high doses.
If you experience the side effects listed in the instructions or they get worse, or you notice any other side effects not listed in the instructions, tell your doctor.
