Apo-Mometasone

Apo-Mometasone

mometasone

Manufacturer:

Apotex

Distributor:

Pharmaforte
Full Prescribing Info
Contents
Mometasone furoate.
Description
APO-MOMETASONE Aqueous Nasal Spray contains white suspension filled in a metered nasal spray device which delivers 140 sprays. Each spray delivers an unscented mist, containing the equivalent of 50 mcg of mometasone furoate.
Excipients/Inactive Ingredients: Benzalkonium Chloride Solution NF/EP, Citric Acid USP, Glycerin (USP)/Glycerol (EP), Microcrystalline Cellulose and Carboxymethylcellulose Sodium NF, Polysorbate 80 NF/EP/BP, Purified Water USP/EP, Sodium Citrate (Dihydrate) USP.
Action
Therapeutic Classification: Corticosteroid for nasal use.
Pharmacology: Mode of action: Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties at doses that are not systemically active.
Clinical Pharmacology: Mometasone furoate, administered as a nasal spray, has a systemic bioavailability of <1% in plasma, using a sensitive assay with a lower quantitation limit (LLOQ) of 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 prior to excretion in urine and bile.
In studies utilizing nasal antigen challenge, Mometasone Aqueous Nasal Spray 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 eosinophils, neutrophils, and epithelial cell adhesion proteins.
Three studies were conducted to assess the safety and efficacy of Mometasone Aqueous Nasal Spray in the treatment of nasal polyps for four month. These included two pivotal trials evaluating doses of 200 mcg once or twice daily and a supportive trial evaluating a dose of 200 mcg once daily. A total of 594 adult patients (ages 18 to 86 years) received Mometasone Aqueous Nasal Spray. The co-primary efficacy endpoints in the pivotal trials were: change from baseline in nasal congestion/obstruction averaged over the first month of treatment; and change from baseline to last assessment in bilateral polyp grade during the entire 4 months of treatment as assessed by nasal endoscopy. Efficacy was demonstrated in both studies at a dose of 200 mcg twice daily and in one study at a dose of 200 mcg once a day. Improvement in other symptoms of nasal polyps (loss of smell, rhinorrhea and postnasal drip) was also observed after a 1-month treatment with 200 mcg, twice daily dose compared to placebo in both studies and in one study after once daily treatment. In the supportive study, patients demonstrated a statistically significant improvement with Mometasone Aqueous nasal spray at a dose of 200 mcg once a day in relief of nasal congestion and reduction of polyp size with 4 months of treatment compared to placebo.
In two trials with 1954 patients 12 years of age and older with signs and symptoms of acute rhinosinusitis for 7 to 28 days prior to baseline, Mometasone Aqueous Nasal Spray 200 μg twice daily was effective in significantly improving symptoms of rhinosinusitis compared to placebo as evaluated by the Major Symptom Score (MSS) composite of symptoms (facial pain/pressure/tenderness, sinus headache, rhinorrhea, post nasal drip, and nasal congestion/stuffiness) during the 15 day treatment period (P02683 p < 0.001; P02692 p = 0.038). In P02683, Mometasone Aqueous Nasal Spray 200 μg twice daily reduced the MSS score (averaged across the 15 day treatment period) by 55.6% from baseline, whereas placebo treatment reduced the MSS by 45.6%. In P02692, Mometasone Aqueous Nasal Spray 200 μg twice daily reduced the MSS score by 48.4% from baseline, whereas placebo treatment reduced the MSS by 41.5% (see Table).

Click on icon to see table/diagram/image

Patients were eligible for study entry only if all signs and symptoms suggestive of bacterial rhinosinusitis were absent. These signs and symptoms were: fever >38.3°C; persistent severe unilateral facial pain or tooth pain; orbital or periorbital facial swelling; dental involvement; and worsening of symptoms after initial improvement. In addition, patients with severe symptoms (on a scale of mild, moderate or severe) in more than three of the five MSS symptom groups were not eligible for study participation. Thus, study subjects generally had mild or moderate rhinosinusitis, likely of non-bacterial origin. Consistent with this, a 500 mg three times a day amoxicillin arm was not significantly different from placebo in reducing the symptoms of rhinosinusitis as evaluated by the MSS. Overall, fewer subjects treated with Mometasone Aqueous Nasal Spray 200 μg twice daily were considered by the treating physician to be treatment failures than those with placebo (p=0.0074). In addition, during the post-treatment follow-up period, the number of recurrences seen with Mometasone was low and comparable to the amoxicillin and placebo treatment groups. Treatment duration beyond 15 days was not evaluated in acute rhinosinusitis.
Toxicology: Preclinical Pharmacology and Toxicology: Preclinical studies demonstrate that mometasone furoate is devoid of androgenic, antiandrogenic, estrogenic or antiestrogenic activity but, like other glucocorticoids, it possesses some antiuterotrophic activity and delays vaginal opening in animal models at high oral doses of 56 mg/kg/day and 280 mg/kg/day.
In cell culture, mometasone furoate was shown to be at least ten times more potent than other steroids, including beclomethasone dipropionate (BDP), betamethasone, hydrocortisone and dexamethasone, at inhibiting the synthesis/release of IL-1, IL-6 and TNFα. Mometasone furoate (IC50 = 0.12 Nm) was also at least six times more potent than BDP and betamethasone at inhibiting IL-5 production. Also, in mixed leukocytes from atopic patients, mometasone was a more potent leukotriene production inhibitor than BDP.
In a preclinical model, the compound has been shown to reduce the accumulation of eosinophils markedly at the site of an allergic reaction. For example, in allergic mice with IgE-mediated allergy, inhaled mometasone furoate at doses as low as 10 micrograms/kg inhibited eosinophil infiltration into bronchoalveolar lavage fluid and the lung bronchi and bronchioles. Additionally, mometasone furoate reduced the number of lymphocytes, and the levels of messenger RNA for the proallergic cytokines IL-4 and IL-5.
It is likely that much of the mechanism for the antiallergic 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 leukocytes of allergic patients. 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.
Mometasone furoate was nonmutagenic in the mouse-lymphoma assay and the salmonella/mammalian-microsome bioassay. Mometasone furoate was negative in the mouse bone-marrow erythrocyte-micronucleus assay, the rat bone-marrow clastogenicity assay, the mouse mitotic male germ-cell clastogenicity assay, and the Chinese hamster lung-cell chromosomal-aberrations assay. At cytotoxic doses in Chinese hamster ovary cell cultures, mometasone furoate induced a dose-related increase in simple chromosome aberrations when continuously exposed (7.5 hours) in the nonactivation phase, but not in the presence of rat liver S9 fraction. This finding is not considered to be of significance in the risk assessment of mometasone furoate, since the S9 phase of the chromosomal-aberration assay and all in vivo assays were negative. Clastogenic responses without human health risk implications have been observed at cytotoxic doses with other corticosteroids, such as dexamethasone.
In subcutaneous Segment I and III studies, mometasone furoate was well tolerated at doses up to 7.5 micrograms/kg (2.6 times the human dose by inhalation). At 15 micrograms/kg prolonged gestation and prolonged and difficult labor 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. Teratology studies were conducted in rats, mice and rabbits by the topical (dermal) and/or subcutaneous routes. Umbilical hernia occurred in rats administered ≥600 micrograms/kg dermally, cleft palate in mice administered 180 micrograms/kg subcutaneously, and gall-bladder agenesis, umbilical hernia, and flexed front paws in rabbits administered ≥150 micrograms/kg dermally. In these teratogenicity studies, there were also reductions in maternal body weight gains, effects on fetal growth (lower fetal body weight and/or delayed ossification) in rats, rabbits and mice, and reduced offspring survival in mice.
No toxicologic 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.
Indications/Uses
Apo-Mometasone Aqueous Nasal Spray is indicated for use in adults and children 3 years of age and older to treat the symptoms of seasonal or perennial allergic rhinitis.
In patients who have a history of moderate to severe symptoms of seasonal allergic rhinitis, prophylactic treatment with Apo-Mometasone Nasal Spray is recommended two to four weeks prior to the anticipated start of the pollen season.
Apo-Mometasone Nasal Spray is indicated for the treatment of nasal polyps in patients 18 years of age and older. Treatment of nasal polyps in pediatric patients less than 18 years of age has not been established.
Apo-Mometasone Nasal Spray is indicated for the treatment of mild to moderate uncomplicated acute rhinosinusitis in patients 12 years of age and older without signs and symptoms of severe bacterial infection.
Dosage/Direction for Use
Treatment of seasonal or perennial allergic rhinitis: Adults (including the elderly) and children 12 years of age and older: The usual recommended dose is two sprays (50 micrograms/spray) into each nostril once daily (total dose 200 micrograms). Once symptoms are controlled, dose reduction to one spray into each nostril (total dose 100 micrograms) may be effective for maintenance.
Children between the ages of 3 and 11 years: The usual recommended dose is one spray (50 micrograms/spray) into each nostril once daily (total dose 100 micrograms).
Administration to young children should be aided by an adult when using Apo-Mometasone Aqueous Nasal Spray.
Clinically significant onset of action occurs as early as 12 hours after the first dose.
Nasal Polyposis: Adults (including the elderly) and adolescents 18 years of age and older: The usual recommended dose for polyposis is two sprays (50 micrograms/spray) in each nostril once daily (total daily dose of 200 mcg). If symptoms are inadequately controlled, the dose may be increased to a daily dose of two sprays in each nostril twice daily (total daily dose of 400 mcg). Dose reduction is recommended following control of symptoms.
Treatment of mild to moderate uncomplicated acute rhinosinusitis: Adults (including the elderly) and children 12 years of age and older: The usual recommended dose is two sprays (50 micrograms/spray) into each nostril twice daily (total daily dose of 400 mcg). If no improvement is seen after 15 days of twice daily administration, alternative therapies should be considered. If symptoms worsen during treatment, the patients should be advised to consult their physician.
Overdosage
Because the systemic bioavailability is <1% (using a sensitive assay with a lower quantitation limit of 0.25 pg/ml) after administration of mometasone furoate via MFNS, overdose is unlikely to require any therapy other than observation.
Inhalation or oral administration of excessive doses of corticosteroids may lead to suppression of hypopituitary-adrenal (HPA) axis function.
Contraindications
Hypersensitivity to any ingredients of APO-MOMETASONE Aqueous Nasal Spray.
Special Precautions
Mometasone Aqueous Nasal Spray should not be used in the presence of untreated localized infection involving the nasal mucosa.
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.
Following 12 months of treatment with Mometasone Aqueous Nasal Spray, 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. As with any long-term treatment, patients using Mometasone Aqueous Nasal Spray over several months or longer should be examined periodically for possible changes in the nasal mucosa. If localized fungal infection of the nose or pharynx develops, discontinuance of Mometasone Aqueous Nasal Spray therapy or appropriate treatment may be required. Persistence of nasopharyngeal irritation may be an indication for discontinuing Mometasone Aqueous Nasal Spray.
Mometasone Aqueous Nasal Spray 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, systemic viral infections or ocular herpes simplex.
There is no evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression following prolonged treatment with Mometasone Aqueous Nasal Spray. However, patients who are transferred from long-term administration of systemically active corticosteroids to Mometasone Aqueous Nasal Spray require careful attention. Systemic corticosteroid withdrawal in such patients may result in adrenal insufficiency for a number of months until recovery of HA axis function. If these patients exhibit signs and symptoms of adrenal insufficiency, systemic corticosteroid administration should be resumed and other modes of therapy and appropriate measures instituted.
During transfer from systemic corticosteroids to Mometasone Aqueous Nasal Spray, some patients may experience symptoms of withdrawal from systemically active corticosteroids (e.g., joint and/or muscular pain, lassitude, and depression initially) despite relief from nasal symptoms and will require encouragement to continue Mometasone Aqueous Nasal Spray therapy. Such transfer may also unmask pre-existing allergic conditions such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy.
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.
Following the use of intranasal aerosolized corticosteroids, instances of nasal septum perforation or increased intraocular pressure have been reported very rarely.
General Nasal Corticosteroid Warning: Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses.
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 patient to a paediatric specialist.
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.
In a placebo-controlled clinical trial in which paediatric patients were administered Mometasone 100 micrograms daily for one year, no reduction in growth velocity was observed.
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents 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.
Safety and efficacy of Mometasone Aqueous Nasal Spray for the treatment of nasal polyposis in children and adolescents less than 18 years of age have not been studied.
Use in acute rhinosinusitis: If signs and symptoms of severe bacterial infection are observed (such as fever, persistent severe unilateral facial/tooth pain, orbital or periorbital facial swelling, or worsening of symptoms after an initial improvement), the patient should be advised to consult their physician immediately. If these signs and symptoms are present at the time of diagnosis, treatment with Mometasone Aqueous Nasal Spray should not be initiated.
Safety and efficacy of Mometasone Aqueous Nasal Spray for the treatment of symptoms of acute rhinosinusitis in children under 12 years of age have not been studied.
Use In Pregnancy & Lactation
There are no adequate or well controlled studies in pregnant women.
As with other nasal corticosteroid preparations, Mometasone Aqueous Nasal Spray should be used in pregnant women, nursing mothers or women of childbearing age only if the potential benefit justifies the potential risk to the mother, fetus or infant. Infants born of mothers who received corticosteroids during pregnancy should be observed carefully for hypoadrenalism.
Adverse Reactions
Clinical Trials Experience: Treatment-related local adverse events reported in clinical studies include headache (8%), epistaxis (i.e., frank bleeding, blood-tinged mucus, and blood flecks) (8%), pharyngitis (4%), nasal burning (2%), nasal irritation (2%), and nasal ulceration, which are typically observed with use of a corticosteroid nasal spray. Epistaxis was generally self-limiting and mild in severity, and occurred at a higher incidence compared to placebo (5%), but at a comparable or lower incidence compared to active control nasal corticosteroids studied (up to 15%). The incidence of all other effects was comparable with that of placebo.
In the pediatric population, the incidence of adverse effects, e.g., headache (3%), epistaxis (6%), nasal irritation (2%) and sneezing (2%) was comparable to placebo.
Post-Marketing Experience: Rarely, immediate hypersensitivity reactions (e.g. bronchospasm, dyspnea) may occur after intranasal administration of mometasone furoate. Very rarely, anaphylaxis, angioedema, chest pain, palpitation and tachycardia have been reported.
Disturbances of taste and smell have been reported very rarely.
Nasal Polyposis: In patients treated for nasal polyposis, the overall incidence of adverse events was comparable to placebo and similar to that observed for patients with allergic rhinitis.
Acute rhinosinusitis: In patients treated for acute rhinosinusitis, the overall incidence of adverse events was comparable to placebo and similar to that observed for patients with allergic rhinitis.
Treatment related adverse events reported most frequently in 200 μg twice daily group include epistaxis (3.7% vs. placebo 2.6%), diarrhoea (2.1% vs. placebo 0.8%), headache (1.7% vs. placebo 2.4%), nausea (1.7% vs. placebo 0.6%) and abdominal pain (1.7% vs. placebo 1.0%).
Vision, Blurred.
Drug Interactions
Drugs that may interact with APO-MOMETASONE Aqueous Nasal Spray include: Ketoconazole.
Caution For Usage
Instructions for Use of Apo-Mometasone Aqueous Nasal Spray: Shake well before each use.
Remove the plastic dust cap.
The very first time the spray is used; prime the pump by pressing downward on the shoulders of the white applicator, using the forefinger and middle finger while supporting the base of the bottle with the thumb. Press down and release the pump ten (10) times or until a fine spray appears. The pump is now ready to use. The pump may be stored unused for up to 2 weeks without repriming. If unused for more than 2 weeks, prime the pump again two (2) times, until a fine spray appears.
Gently blow nose to clear nostrils. Close one nostril using the finger. Tilt head forward slightly and, keeping the bottle upright, carefully insert the nasal applicator into the other nostril.
For each spray, press firmly downward once on the shoulder of the white applicator, using the forefinger and middle finger while supporting the base of the bottle with the thumb. Spray while breathing gently inward through the nostril, with the mouth closed.
Then breathe out through the mouth.
Repeat in the other nostril.
Replace the plastic dust cap after each use.
The correct amount of medication in each spray can only be assured up to 140 sprays from the bottle even though the bottle may not be completely empty. The patient should keep track of the number of sprays used from each bottle of APO-MOMETASONE Aqueous Nasal Spray, and discard the bottle after using 140 sprays.
Cleaning: To clean the nasal applicator, remove the plastic dust cap and pull gently upward on the white nasal applicator so that it comes free. Wash the applicator and dust cap under a cold-water tap.
Do not try to unblock the nasal applicator by inserting a pin or other sharp object as this will damage the applicator and cause the patient not to get the right dose of medicine.
Dry and replace the nasal applicator followed by the plastic dust cap.
Re-prime the pump with 2 sprays when first used after cleaning.
Storage
Store at or below 30°C, do not freeze. Protect from light.
ATC Classification
R01AD09 - mometasone ; Belongs to the class of topical corticosteroids used for prophylaxis and treatment of allergic rhinitis.
Presentation/Packing
Aqueous nasal spray 50 mcg/metered spray (white suspension) x 140 sprays x 1's.
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