Forinex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FORINEX® (FORINEX)

Composition:

Active substance: mometasone furoate;

1 dose (100 mg) of spray contains micronized mometasone furoate 50 mcg;

Excipients: benzalkonium chloride solution; citric acid monohydrate; glycerin; sodium carboxymethylcellulose-microcrystalline cellulose; polysorbate 80; sodium citrate; water for injections.

Pharmaceutical form. Nasal spray, suspension.

Main physicochemical properties: white suspension.

Pharmacotherapeutic group.

Anti-inflammatory and other drugs for local use in nasal cavity disorders. Corticosteroids. ATC code R01AD09.

Pharmacological Properties

Pharmacodynamics

Mometasone furoate is a synthetic corticosteroid for topical use with pronounced anti-inflammatory activity. The local anti-inflammatory effect of mometasone furoate occurs 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 suppress the release of mediators of allergic reactions. Mometasone furoate significantly reduces the synthesis/release of leukotrienes from leukocytes of patients suffering from allergic diseases. In cell culture studies, mometasone furoate demonstrated 10-fold greater activity than other steroids—including beclomethasone dipropionate, betamethasone, hydrocortisone, and dexamethasone—in inhibiting the synthesis/release of IL-1, IL-5, IL-6, and TNFα. It is also a potent inhibitor of Th2 cytokine production, specifically IL-4 and IL-5, from human CD4+ T-cells. Mometasone furoate is also six times more active than beclomethasone dipropionate and betamethasone in suppressing IL-5 production.

In challenge studies involving antigen application to the nasal mucosa, aqueous nasal spray of mometasone furoate demonstrated high anti-inflammatory activity in both the early and late phases of the allergic response. This was confirmed by reductions (compared to placebo) in histamine levels and eosinophil activity, as well as decreased numbers (compared to baseline) of eosinophils, neutrophils, and epithelial cell adhesion proteins.

Marked clinical effect within the first 12 hours of treatment with aqueous nasal spray of mometasone furoate was achieved in 28% of patients with seasonal allergic rhinitis. On average (50%), symptom relief occurred within 35.9 hours. In addition, mometasone furoate demonstrated significant efficacy in alleviating ocular symptoms (redness, tearing, itching) in patients with seasonal allergic rhinitis.

In clinical studies involving patients with nasal polyps, mometasone furoate spray demonstrated significant clinical efficacy in relieving nasal congestion, reducing polyp size, and restoring the sense of smell compared to placebo.

In clinical studies involving patients aged 12 years and older, mometasone furoate nasal spray at a dose of 200 mcg twice daily demonstrated high efficacy in reducing symptoms of rhinosinusitis compared to placebo. Over 15 days of treatment, rhinosinusitis symptoms were assessed using the Major Symptom Score (MSS) scale (facial pain, pressure in sinuses, pain on palpation, sinus pain, rhinorrhea, postnasal drip, and nasal congestion). The efficacy of amoxicillin 500 mg three times daily did not significantly differ from placebo in reducing rhinosinusitis symptoms on the MSS scale. During the post-treatment follow-up period, the recurrence rate in the mometasone furoate group was low and comparable to the amoxicillin and placebo groups. Treatment duration for acute rhinosinusitis beyond 15 days was not evaluated.

Pharmacokinetics

The systemic bioavailability of mometasone furoate following administration as a nasal spray is < 1% in plasma (based on data obtained using a sensitive method; the lower limit of quantification is 0.25 pg/mL). Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract, and the small amount that may be swallowed and absorbed undergoes extensive first-pass metabolism, resulting in excretion primarily as metabolites in bile and to a lesser extent in urine.

Clinical characteristics.

Indications.

For the treatment of seasonal or perennial allergic rhinitis in adults and children aged 3 years and older. Prophylactic treatment of moderate to severe allergic rhinitis should be initiated 4 weeks before the expected start of the 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.

For the treatment of symptoms of acute rhinosinusitis without signs of severe bacterial infection in adults and children aged 12 years and older.

For the 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 mometasone furoate or to any of the excipients of the medicinal product.

Forinex® nasal spray should not be used in the presence of untreated local nasal mucosal infections, such as herpes simplex.

Since nasal corticosteroids may impair wound healing, the medicinal product should not be administered to patients who have recently undergone nasal surgery or experienced nasal trauma until healing has occurred.

Interaction with other medicinal products and other forms of interaction.

(See section "Special precautions for use").

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 side effects; in such cases, patients should be monitored for the occurrence of systemic corticosteroid adverse effects.

In a clinical study, mometasone furoate nasal spray was administered concomitantly with a non-sedating oral antihistamine (loratadine). The pharmacokinetic parameters and safety profile remained unchanged for both drugs.

Special precautions for use.

The medicinal product Forinex® should be used with caution or not used at all in patients with active or latent tuberculosis infection of the respiratory tract, as well as in those with untreated fungal, bacterial, or systemic viral infections.

As with any long-term treatment, patients using the product for several months or longer should undergo periodic examinations to detect possible changes in the nasal mucosa. After 12 months of treatment with mometasone furoate, no signs of atrophy of the nasal mucosa have been observed; furthermore, mometasone furoate has been shown to promote normalization of the histological appearance of the nasal mucosa.

Forinex® contains benzalkonium chloride, which may cause irritation or swelling of the nasal mucosa, particularly with prolonged use.

In the event of development of a localized fungal infection of the nose or throat, treatment with the product may need to be discontinued and appropriate therapy initiated. Persistent irritation of the nasal or pharyngeal mucosa may also be an indication for discontinuation of treatment with the product.

Forinex® is not recommended for use in cases of nasal septum perforation (see section "Side effects").

In clinical studies, the incidence of epistaxis was higher compared to placebo. Epistaxis was usually not severe and resolved spontaneously (see section "Side effects").

Patients who are switching to treatment with Forinex® after prolonged systemic corticosteroid therapy require careful monitoring. Discontinuation of systemic corticosteroids in such patients may lead to adrenal insufficiency for several months until recovery of the hypothalamic-pituitary-adrenal axis. If such patients develop signs and symptoms of adrenal insufficiency or withdrawal symptoms (e.g., joint or muscle pain, fatigue, and depression in the initial phase), despite improvement in nasal symptoms, systemic corticosteroid therapy should be reinstated, and alternative treatment regimens and appropriate measures should be considered. After such a transition, pre-existing allergic conditions such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy, may also become apparent.

Use of doses higher than recommended may lead to clinically significant adrenal suppression. If higher than recommended doses are required, consideration should be given to the use of additional systemic corticosteroids during periods of stress or planned surgical procedures.

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

Unilateral nasal polyps, which are unusual and rarely occur, especially if accompanied by ulceration or bleeding, should be investigated more thoroughly.

Patients receiving corticosteroids may potentially have reduced immune responsiveness and should be warned about the increased risk of infection upon exposure to certain infectious diseases (e.g., varicella, measles) and the need to consult a physician if such exposure occurs.

The safety and efficacy of mometasone furoate in the treatment of nasal polyps in children and adolescents under 18 years of age have not been studied.

During transition from systemic corticosteroid therapy to treatment with Forinex®, some patients may experience corticosteroid withdrawal symptoms alongside improvement in nasal symptoms. Such patients should be specifically reassured about the appropriateness of continuing treatment with Forinex®.

Systemic effects of corticosteroids

Systemic effects may occur during treatment with intranasal corticosteroids, particularly when high doses are used over a prolonged period. These effects are much less common than with oral corticosteroids and may vary among different patients and with different corticosteroids. Potential systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma, and less frequently, a range of psychological or behavioral effects such as psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression (particularly in children).

Effect on growth in children

It is recommended that the height of children receiving long-term treatment with intranasal corticosteroids be measured regularly. If growth retardation occurs, therapy should be reviewed with the aim of reducing the dose of the intranasal corticosteroid, if possible, to the lowest dose at which effective symptom control is maintained. In addition, the patient should be referred for evaluation by a pediatrician.

Cases of increased intraocular pressure have been reported after use of intranasal corticosteroids (see section "Side effects").

Visual disturbances may occur with both systemic and topical corticosteroids (including intranasal, inhaled, and intraocular administration). If symptoms such as blurred vision or other visual disturbances occur, the patient should be referred to an ophthalmologist for evaluation of possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after use of systemic and topical corticosteroids.

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

The safety and efficacy of mometasone furoate in the treatment of rhinosinusitis symptoms in children under 12 years of age have not been studied.

Non-nasal symptoms

Although Forinex® nasal spray controls nasal symptoms in most patients, concomitant use of appropriate additional therapy may help further alleviate other symptoms, particularly those affecting the eyes.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of mometasone furoate in pregnant women are lacking or limited. Reproductive toxicity has been observed in animal studies. Like other intranasal corticosteroids, mometasone furoate nasal spray should be used during pregnancy only if the expected benefit justifies the potential risk to the mother, fetus, or infant. Infants born to mothers who used corticosteroids during pregnancy should be carefully monitored for possible adrenal insufficiency.

Breastfeeding. It is unknown whether mometasone furoate passes into breast milk. As with other intranasal corticosteroids, breastfeeding should be discontinued or treatment with Forinex® nasal spray should be discontinued or avoided, taking into account the benefits of breastfeeding for the child and the therapeutic benefit for the woman.

Fertility. There are no clinical data on the effect of mometasone furoate on fertility. Animal studies have shown reproductive toxicity, but no effect on fertility was observed.

Ability to affect reaction speed when driving vehicles or operating machinery.

Unknown.

Method of Administration and Dosage.

Before using a new bottle of the medication, it should be calibrated. Calibration is performed by approximately 10 actuations of the dosing device, which establishes a consistent delivery of the drug, so that each actuation releases approximately 100 mg of suspension containing 50 mcg of mometasone (one dose). If the nasal spray has not been used for 14 days or longer, it is necessary to re-prime the device by 2 actuations until a full spray is observed before the next use. Do not pierce the nozzle before starting use.

The bottle should be shaken vigorously before each administration.

If the nozzle becomes clogged, remove the plastic cap by pressing gently on the white ring, carefully detach the nozzle, rinse it with warm running water, dry it thoroughly, and reattach it to the bottle. Do not attempt to clean the nozzle with a needle or any other sharp object, as this may damage the spray pump.

Regular cleaning of the nozzle is very important.

Before each use, the nose should be cleared thoroughly of mucus.

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

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 the full therapeutic effect.

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

Adjunctive treatment of acute sinusitis episodes. For adults (including elderly patients) and children aged 12 years and older, the recommended therapeutic dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to 4 sprays into each nostril twice daily (total daily dose – 800 mcg). After symptom relief, the dose should be reduced.

Acute rhinosinusitis. For adults and children aged 12 years and older, the recommended therapeutic dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg).

Nasal polyps. For patients aged 18 years and older (including elderly patients), the recommended dose is 2 sprays (50 mcg each) into each nostril twice daily (total daily dose – 400 mcg). After achieving the clinical effect, the dose should be reduced to 2 sprays into each nostril once daily (total daily dose – 200 mcg).

Children.

The safety and efficacy of mometasone furoate in the treatment of nasal polyps in children and adolescents under 18 years of age, symptoms of rhinosinusitis in children under 12 years of age, and seasonal or perennial allergic rhinitis in children under 3 years of age have not been established.

Overdose.

Overdose is unlikely to require any therapy other than observation.

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

Adverse reactions

In clinical trials of allergic rhinitis, nasal bleeding was self-limiting and mild, occurred slightly more frequently than with placebo (5%), but with the same frequency or less frequently than with other investigational intranasal corticosteroids used as active controls (in some of these, the incidence of nasal bleeding was up to 15%). The incidence of other adverse events was comparable to that observed with placebo.

In patients with nasal polyps, the overall incidence of adverse reactions was similar to that observed in patients with allergic rhinitis.

In children, the incidence of adverse events was comparable to that with placebo, for example: epistaxis (6%), headache (3%), nasal irritation (2%), and sneezing (2%).

Table 1 lists adverse reactions (≥1%) observed during clinical trials in patients with allergic rhinitis or nasal polyposis, as well as during post-marketing use. Adverse reactions are listed by organ systems according to MedDRA (Medical Dictionary for Regulatory Activities). The frequency of adverse reactions is defined using the following categories: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100). In post-marketing studies, the frequency of adverse reactions cannot be estimated from available data and is therefore listed as "unknown".

Table 1

* Adverse reaction observed with twice-daily administration for the treatment of nasal polyps.

† Adverse reaction observed uncommonly with twice-daily administration for the treatment of nasal polyps.

In patients with acute rhinosinusitis, the overall incidence of adverse events was comparable to that with placebo and similar to the incidence observed in patients with other indications. Treatment-related adverse reactions observed in clinical trials in more than 2% of patients are listed in Table 2.

Table 2

The most common adverse reaction, nasal bleeding, occurred at approximately the same frequency in the placebo group (2.6%) and the mometasone furoate group (2.9% and 3.7%, respectively).

Systemic effects of nasal corticosteroids may occur, especially with prolonged use of high doses.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 ºC. Do not freeze.

Keep out of reach and sight of children.

Packaging.

140 doses per bottle. 1 bottle per carton (packaged from bulk produced by Apotex Inc., Canada).

Prescription status. Prescription only.

Manufacturer: JSC "Farmak".

Manufacturer's address and site of operations:

74, Kyrylivska Street, Kyiv, 04080, Ukraine.