Respizen Nasal Spray

Mometasone Aqueous Nasal Spray

Each spray delivers:

Mometasone Furoate IP 50 mcg

Composition:

Mometasone Furoate IP…………………. 0.05% w/v

Preservative:

Benzalkonium Chloride IP……………… 0.01 % w/v

Phenylethyl Alcohol IP…………………. 0.25 % w/v

Excipients q.s.

Nasal spray Each spray delivers Mometasone Furoate 50 mcg

4.1 Therapeutic indication

• For treatment of symptoms of seasonal or perennial rhinitis in adults only.
• For the treatment of nasal symptoms of seasonal allergic and perennial allergic rhinitis, in adults and paediatric patients 2 years of age and older.

4.2 Posology and method of administration

Seasonal Allergic or Perennial Rhinitis

Adults (including older patients) and children 12 years of age and older

The usual recommended dose is two actuations (50 micrograms/actuation) in each nostril once daily (total dose 200 micrograms). Once symptoms are controlled, dose reduction to one actuation in each nostril (total dose 100 micrograms) may be effective for maintenance. If symptoms are inadequately controlled, the dose may be increased to a maximum daily dose of four actuations in each nostril once daily (total dose 400 micrograms). Dose reduction is recommended following control of symptoms.

Paediatric population

Children between the ages of 2 and 11 years

The usual recommended dose is one actuation (50 micrograms/actuation) in each nostril once daily (total dose 100 micrograms).

Mometasone furoate nasal spray, suspension demonstrated a clinically significant onset of action within 12 hours after the first dose in some patients with seasonal allergic rhinitis; however, full benefit of treatment may not be achieved in the first 48 hours. Therefore, the patient should continue regular use to achieve full therapeutic benefit.

Treatment with mometasone furoate nasal spray, suspension may need to be initiated some days before the expected start of the pollen season in patients who have a history of moderate to severe symptoms of seasonal allergic rhinitis.

Paediatric population

Seasonal Allergic Rhinitis and Perennial Rhinitis

The safety and efficacy of mometasone furoate nasal spray in children under 2 years of age have not been established.

Method of administration

Prior to administration of to the first dose, shake container well.

After initial priming of the Mometasone furoate nasal spray, suspension pump (usually 10 actuations, until a uniform spray is observed), each actuation delivers approximately 100 mg of mometasone furoate suspension, containing mometasone furoate monohydrate equivalent to 50 micrograms mometasone furoate. If the pump is not used for 14 days or longer, reprime the pump with 2 actuations, a uniform spray is observed, before next use.

Shake container well before each use. The bottle should be discarded after the labelled number of actuations or within 2 months of first use.

Do not use a pin or sharp object to unblock the nozzle as this will damage the spray mechanism.

4.3 Contraindications

• Hypersensitivity to Mometasone furoate or to any of the excipients listed in the formulation.
• Mometasone furoate nasal spray should not be used in the presence of untreated localized infection involving the nasal mucosa, such as herpes simplex.
• Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal surgery or trauma should not use a nasal corticosteroid until healing has occurred.

4.4 Special warnings and precautions for use

Immunosuppression

Mometasone furoate nasal spray, suspension should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract, or in untreated fungal, bacterial or systemic viral infections. Patients receiving corticosteroids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.

Local Nasal Effects

Following 12 months of treatment with mometasone furoate nasal spray, suspension in a study of patients with perennial rhinitis, there was no evidence of atrophy of the nasal mucosa; also, mometasone furoate tended to reverse the nasal mucosa closer to a normal histologic phenotype. Nevertheless, patients using mometasone furoate nasal spray, suspension over several months or longer should be examined periodically for possible changes in the nasal mucosa. If localised fungal infection of the nose or pharynx develops, discontinuance of mometasone furoate nasal spray, suspension therapy or appropriate treatment may be required. Persistence of nasopharyngeal irritation may be an indication for discontinuing mometasone furoate nasal spray, suspension.

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

In clinical studies, epistaxis occurred at a higher incidence compared to placebo. Epistaxis was generally self-limiting and mild in severity.

Mometasone furoate nasal spray, suspension contains benzalkonium chloride which may cause irritation or swelling inside the nose, especially if used for a long time.

Systemic Effects of Corticosteroids

Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may 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 effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

Following the use of intranasal corticosteroids, instances of increased intraocular pressure have been reported.

Patients who are transferred from long-term administration of systemically active corticosteroids to mometasone furoate nasal spray, suspension require careful attention. Systemic corticosteroid withdrawal in such patients may result in adrenal insufficiency for a number of months until recovery of HPA axis function. If these patients exhibit signs and symptoms of adrenal insufficiency or symptoms of withdrawal (e.g., joint and/or muscular pain, lassitude, and depression initially) despite relief from nasal symptoms, systemic corticosteroid administration should be resumed and other modes of therapy and appropriate measures instituted. Such transfer may also unmask pre-existing allergic conditions, such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy.

Treatment with higher than recommended doses may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Effect on Growth in Paediatric Population

It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid if possible, to the lowest dose at which effective control of symptoms is maintained. In addition, consideration should be given to referring the patient to a paediatric specialist.

Non-nasal Symptoms

Although mometasone furoate nasal spray, suspension will control the nasal symptoms in most patients, the concomitant use of appropriate additional therapy may provide additional relief of other symptoms, particularly ocular symptoms.

Visual disturbance

Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) corticosteroid use. If a patient present with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

4.5 Drugs interactions

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

A clinical interaction study was conducted with loratadine. No interactions were observed.

4.6 Use in special populations

Pregnancy

There are no or limited amount of data from the use of mometasone furoate in pregnant women. Studies in animals have shown reproductive toxicity. As with other nasal corticosteroid preparations, mometasone furoate nasal spray, suspension should not be used in pregnancy unless the potential benefit to the mother justifies any potential risk to the mother, foetus or infant.

Infants born of mothers who received corticosteroids during pregnancy should be observed carefully for hypoadrenalism.

Breast-feeding

It is unknown whether mometasone furoate is excreted in human milk. As with other nasal corticosteroid preparations, a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from mometasone furoate nasal spray, suspension therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

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

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

Epistaxis was generally self-limiting and mild in severity. Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.

Tabulated list of adverse reactions

Paediatric population

In the paediatric population, the recorded adverse events are epistaxis, headache, nasal irritation and sneezing.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Symptoms

Inhalation or oral administration of excessive doses of corticosteroids may lead to suppression of HPA axis function.

Management

Because of the negligible (≤ 0.1%) systemic bioavailability of mometasone furoate nasal spray, suspension overdose is unlikely to require any therapy other than observation, followed by initiation of the appropriate prescribed dosage.

5.1 Mechanism of Action

Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties at doses that are not systemically active.

It is likely that much of the mechanism for the anti-allergic and anti-inflammatory effects of mometasone furoate lies in its ability to inhibit the release of mediators of allergic reactions. Mometasone furoate significantly inhibits the release of leukotrienes from leucocytes of allergic patients.

In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNFα; it is also a potent inhibitor of leukotriene production. In addition, it is an extremely potent inhibitor of the production of the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.

5.2 Pharmacodynamic properties

In studies utilising nasal antigen challenge, mometasone furoate nasal spray, suspension has shown anti-inflammatory activity in both the early- and late - phase allergic responses. This has been demonstrated by decreases (vs placebo) in histamine and eosinophil activity and reductions (vs baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins.

In 28% of the patients with seasonal allergic rhinitis, mometasone furoate nasal spray, suspension demonstrated a clinically significant onset of action within 12 hours after the first dose. The median (50%) onset time of relief was 35.9 hours.

5.3 Pharmacokinetic properties

Absorption

Mometasone furoate, administered as an aqueous nasal spray, has a systemic bioavailability of < 1% in plasma, using a sensitive assay with a lower quantitation limit of 0.25 pg/ml.

Distribution

Not applicable as mometasone is poorly absorbed via the nasal route.

Biotransformation

The small amount that may be swallowed and absorbed undergoes extensive first-pass hepatic metabolism.

Elimination

Absorbed mometasone furoate is extensively metabolized and the metabolites are excretedin urine and bile.

6.1 Animal Toxicology or Pharmacology

No toxicological effects unique to mometasone furoate exposure were demonstrated. All observed effects are typical of this class of compounds and are related to exaggerated pharmacologic effects of glucocorticoids.

Preclinical studies demonstrate that mometasone furoate is devoid of androgenic, antiandrogenic, estrogenic or antiestrogenic activity but, like other glucocorticoids, it exhibits some antiuterotrophic activity and delays vaginal opening in animal models at high oral doses of 56 mg/kg/day and 280 mg/kg/day.

Like other glucocorticoids, mometasone furoate showed a clastogenic potential in-vitro at high concentrations. However, no mutagenic effects can be expected at therapeutically relevant doses.

In studies of reproductive function, subcutaneous mometasone furoate, at 15 micrograms/kg prolonged gestation and prolonged and difficult labour occurred with a reduction in offspring survival and body weight or body weight gain. There was no effect on fertility.

Like other glucocorticoids, mometasone furoate is a teratogen in rodents and rabbits. Effects noted were umbilical hernia in rats, cleft palate in mice and gallbladder agenesis, umbilical hernia, and flexed front paws in rabbits. There were also reductions in maternal body weight gains, effects on foetal growth (lower foetal body weight and/or delayed ossification) in rats, rabbits and mice, and reduced offspring survival in mice.

The carcinogenicity potential of inhaled mometasone furoate (aerosol with CFC propellant and surfactant) at concentrations of 0.25 to 2.0 micrograms/l was investigated in 24-month studies in mice and rats. Typical glucocorticoid-related effects, including several non-neoplastic lesions, were observed. No statistically significant dose-response relationship was detected for any of the tumour types.

Mometasone furoate, the active component of Respizen Nasal Spray, 50 mcg, is an anti-inflammatory corticosteroid having the chemical name, 9,21-Dichloro-11ß,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione17-(2 furoate) monohydrate, and the following chemical structure:

Molecular formula: C₂₇H₃₀C_l2O₆•H₂O

Molecular weight: 539.45. 

8.1 Shelf-life

Refer on pack

8.2 Storage and handing instructions

Store below 25°C. Protect from light. Do not freeze.

Keep out of reach of children.

SHAKE WELL BEFORE EACH USE.

FOR NASAL USE ONLY.

Replace cap after every use.

Local Nasal Effect

Patients should be informed that treatment with RESPIZEN Nasal Spray 50 mcg may be associated with adverse reactions which include epistaxis (nose bleed) and nasal septum perforation. Candida infection may also occur. Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septum ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred. Patients should be cautioned not to spray RESPIZEN Nasal Spray 50 mcg directly onto the nasal septum.

Glaucoma and Cataracts

Patients should be informed that nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. Patients should be cautioned not to spray RESPIZEN Nasal Spray 50 mcg into the eyes.

Immunosuppression

Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles, and patients should also be advised that if they are exposed, medical advice should be sought without delay.

Use Regularly for Best Effect

Patients should use RESPIZEN Nasal Spray 50 mcg on a regular basis for optimal effect. Improvement in nasal symptoms of allergic rhinitis has been shown to occur within 1 to 2 days after initiation of dosing. Maximum benefit is usually achieved within 1 to 2 weeks after initiation of dosing. Patients should not increase the prescribed dosage but should contact their physician if symptoms do not improve, or if the condition worsens. Administration to young children should be aided by an adult.

If a patient missed a dose, the patient should be advised to take the dose as soon as they remember. The patient should not take more than the recommended dose for the day.

09.10.2024