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Epistaxis

Epistaxis was observed more frequently in patients with allergic rhinitis and patients with chronic rhinosinusitis with nasal polyps who received NASONEX than those who received placebo [see Adverse Reactions (6.1)].

Candida Infection

Localized infections of the nose and pharynx with Candida albicans has occurred from nasal administration of mometasone furoate. When such an infection develops, use of NASONEX should be discontinued and appropriate local or systemic therapy instituted, if needed.

Nasal Septum Perforation

Instances of nasal septum perforation occurred in patients following the nasal application of corticosteroids, including NASONEX. As with any long-term topical treatment of the nasal cavity, patients using NASONEX over several months or longer should be examined periodically for possible changes in the nasal mucosa.

Impaired Wound Healing

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.

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Hypercorticism and adrenal suppression may occur when nasal corticosteroids, including NASONEX, are used at higher-than-recommended dosages [see Dosage and Administration (2)] or in patients at risk for such effects. If such changes occur, the dosage of NASONEX should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy.

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Corticosteroids, including NASONEX, may cause a reduction in growth velocity when administered to pediatric patients. Routinely, monitor the growth of pediatric patients receiving NASONEX. To minimize the systemic effects of nasal corticosteroids, including NASONEX, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations (8.4)].

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The following clinically significant adverse reactions are described elsewhere in labeling:

• Epistaxis, Ulcerations, Candida albicans Infection, Impaired Wound Healing [see Warnings and Precautions (5.1)]

• Glaucoma and Cataracts [see Warnings and Precautions (5.2)]

• Immunosuppression and Risk of Infections [see Warnings and Precautions (5.4)]

• Hypercorticism and Adrenal Suppression, including Growth Reduction [see Warnings and Precautions (5.5, 5.6), Use in Specific Populations (8.4)]

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Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Allergic Rhinitis

Adults and pediatric patients 12 years of age and older

In controlled U.S. and international clinical studies, a total of 3210 adult and pediatric patients 12 years and older with allergic rhinitis received treatment with NASONEX at doses of 50 to 800 mcg/day. The majority of patients (n=2103) were treated with 200 mcg/day. A total of 350 adult and pediatric patients 12 years and older have been treated for one year or longer. Adverse reactions did not differ significantly based on age, sex, or race. Four percent or less of patients in clinical trials discontinued treatment because of adverse events and the discontinuation rate was similar for the vehicle and active comparators.

All adverse reactions (regardless of relationship to treatment) reported by 5% or more of adult and pediatric patients ages 12 years and older who received NASONEX, 200 mcg/day vs. placebo and that were more common with NASONEX than placebo, are displayed in Table 1 below.

Table 1: Adult and Pediatric Patients 12 Years and Older – Adverse Reactions from Controlled Clinical Trials in Seasonal Allergic and Perennial Allergic Rhinitis (Percent of Patients Reporting)

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Other adverse reactions which occurred in less than 5% but greater than or equal to 2% of adult and pediatric patients (ages 12 years and older) treated with NASONEX 200-mcg/day (regardless of relationship to treatment), and more frequently than in the placebo group included: arthralgia, asthma, bronchitis, chest pain, conjunctivitis, diarrhea, dyspepsia, earache, flu-like symptoms, myalgia, nausea, and rhinitis.

Chronic Rhinosinusitis with Nasal Polyps

Adults 18 years of age and older

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Risk Summary

Mometasone is minimally absorbed systemically following nasal use, and maternal use is not expected to result in fetal exposure to the drug. Available data from observational studies of mometasone use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies with pregnant mice, rats, or rabbits (subcutaneous, subcutaneous/topical dermal/oral, and topical dermal/oral, respectively), mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m2 or AUC basis [see Data]. However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at a dose less than the maximum recommended daily intranasal dose (MRDID) (on a mcg/m2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at approximately 2 times the MRDID (on a mcg/m2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure less than the MRDID (on a mcg/m2 basis with maternal topical dermal doses of 20 mcg/kg and above).

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Risk Summary

There are no available data on the presence of NASONEX in human milk, the effects on the breastfed child, or the effects on milk production. However, mometasone is minimally absorbed systemically by the mother following nasal use, and breastfeeding is not expected to result in exposure of the infant to mometasone. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NASONEX and any potential adverse effects on the breastfed infant from NASONEX or from the underlying maternal condition.

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The safety and effectiveness of NASONEX for prophylaxis of the nasal symptoms of seasonal allergic rhinitis in pediatric patients 12 years of age and older have been established [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. Use of NASONEX for this indication is supported by evidence from controlled trials in adult and pediatric patients 12 years of age and older [see Clinical Studies (14.1)].

The safety and effectiveness of NASONEX for the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients less than 18 years of age have not been established. Effectiveness was not demonstrated in one 4-month trial conducted to evaluate the safety and efficacy of NASONEX in the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients 6 to 17 years of age. The primary objective of the study was to evaluate safety; efficacy parameters were collected as secondary endpoints. A total of 127 patients with chronic rhinosinusitis with nasal polyps were randomized to placebo or NASONEX 100 mcg once or twice daily (patients 6 to 11 years of age) or 200 mcg once or twice daily (patients 12 to 17 years of age). The results of this trial did not support the efficacy of NASONEX in the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients. The adverse reactions reported in this trial were similar to the adverse reactions reported in patients 18 years of age and older with chronic rhinosinusitis with nasal polyps.

Effect on Growth

Controlled clinical studies have shown nasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with nasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch up” growth following discontinuation of treatment with nasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving nasal corticosteroids, including NASONEX, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. To minimize the systemic effects of nasal corticosteroids, including NASONEX, each patient should be titrated to his/her lowest effective dose.

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A total of 280 patients above 64 years of age with allergic rhinitis or chronic rhinosinusitis with nasal polyps (age range 64 to 86 years) have been treated with NASONEX for up to 3 or 4 months, respectively. No observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.

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Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Local Nasal Adverse Reactions

Patients should be informed that treatment with NASONEX 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 [see Warnings and Precautions (5.1)]. Patients should be cautioned not to spray NASONEX directly onto the nasal septum
Glaucoma and Cataracts

Advise patients that long-term use of nasal and inhaled corticosteroids may increase the risk of some eye problems (glaucoma or cataracts); regular eye examinations should be considered. Patients should be cautioned not to spray NASONEX into the eyes [see Warnings and Precautions (5.2)].
Immunosuppression and Risk of Infections

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 [see Warnings and Precautions (5.4)].
Use Regularly for Best Effect

Patients should use NASONEX 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 administer the dose as soon as they remember. The patient should not use more than the recommended dose for the day.

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What is NASONEX?

NASONEX is a man-made (synthetic) corticosteroid medicine that is used to:

• prevent nasal symptoms of seasonal allergic rhinitis in people 12 years of age and older.

• treat chronic rhinosinusitis with nasal polyps in people 18 years and older. It is not known if NASONEX is safe and effective in children under:

• 12 years of age to prevent nasal symptoms of seasonal allergic rhinitis.

• 18 years of age to treat chronic rhinosinusitis with nasal polyps.

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How should I use NASONEX?

• Use NASONEX exactly as prescribed by your healthcare provider.

• This medicine is for use in the nose only. Do not spray it into your mouth or eyes.

• An adult should supervise a child using this medicine.

• For best results, you should keep using NASONEX regularly each day without missing a dose. If you do miss a dose of NASONEX, take it as soon as you remember. However, do not take more than the daily dose prescribed by your healthcare provider.

• Do not use NASONEX more often than prescribed. Ask your healthcare provider if you have any questions.

• For detailed instructions on how to use NASONEX, see the “Patient Instructions for Use” at the end of this leaflet.

• See your healthcare provider regularly to check your symptoms while taking NASONEX and to check for side effects.

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‘Nasal’ replaces ‘intranasal’ throughout section.

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5.4 Immunosuppression and Risk of Infections

5.5 Hypercortism and Adrenal Suppression

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Systemic and local corticosteroid use may result in the following:

• Immunosuppression and Risk of Infections

• Hypercortism and Adrenal Suppression

6.1 Clinical Trials Experiences

‘reactions’ replaces events’ throughout.

Nasal Congestion Associated with Seasonal Allergic Rhinitis

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A total of 1008 patients aged 12 years and older received NASONEX 200 mcg/day (n=506) or placebo (n=502) for 15 days. Adverse reactions that occurred more frequently in patients treated with NASONEX than in patients with the placebo included sinus headache (1.2% in NASONEX group vs. 0.2% in placebo) and epistaxis (1% in NASONEX group vs. 0.2% in placebo) and the overall adverse reaction profile was similar to that observed in the other allergic rhinitis trials.

8.1 Pregnancy

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Risk Summary

There are no adequate and well-controlled clinical studies of NASONEX in pregnant women. In animal reproduction studies with pregnant mice, rats, or rabbits, mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m2 or AUC basis [see Data]. However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at a dose less than the maximum recommended daily nasal dose (MRDID) (on a mcg/m2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at approximately 2 times the MRDID (on a mcg/m2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure less than the MRDID (on a mcg/m2 basis with maternal topical dermal doses of 20 mcg/kg and above).

In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 10 times the MRDID (on a mcg/m2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at a dose approximately 6 times the MRDID (on a mcg/m2 basis with maternal topical dermal doses of 300 mcg/kg and above).

In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at a dose less than the MRDID (on a mcg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings at a dose less than the MRDID (on a mcg/m2 basis with a maternal subcutaneous dose of 7.5 mcg/kg).

Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at doses approximately 6 times the MRDID (on a mcg/m2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at a dose approximately 30 times of the MRDID (on a mcg/m2 basis with a maternal oral dose of 700 mcg/kg). At approximately 110 times the MRDID (on a mcg/m2 basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted    or resorbed. No effects were observed at a dose approximately 6 times the MRDID (on a mcg/m2 basis with a maternal oral dose of 140 mcg/kg).

8.2 Lactation

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Risk Summary

There are no available data on the presence of NASONEX in human milk, the effects on the breastfed child, or the effects on milk production. Other corticosteroids are excreted in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NASONEX and any potential adverse effects on the breastfed infant from NASONEX or from the underlying maternal condition.

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Immunosuppression and Risk of Infections

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In vitro studies have confirmed the primary role of cytochrome CYP3A4 in the metabolism of this compound.

Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, mometasone furoate and potentially increase the risk for systemic corticosteroid side effects. Caution should be exercised when considering the coadministration of NASONEX Nasal Spray 50 mcg with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin). Consider the benefit of coadministration versus the potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side effects.

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Glaucoma and cataracts may be reported with systemic and topical (including intranasal, inhaled and intraocular) corticosteroid use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use NASONEX long term.

17.2 Glaucoma and Cataracts

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