Mometasone Nasal Spray: Package Insert / Prescribing Info

1.1 Prophylaxis of Seasonal Allergic Rhinitis

Mometasone furoate nasal spray is indicated for the prophylaxis of the nasal symptoms of seasonal allergic rhinitis in adult and pediatric patients 12 years and older.

1.2 Treatment of Chronic Rhinosinusitis with Nasal Polyps

Mometasone furoate nasal spray is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients 18 years of age and older.

2.1 Preparation and Administration

Administer mometasone furoate nasal spray by the nasal route only.

Initial Priming

Prior to initial use of mometasone furoate nasal spray, the pump must be primed by actuating ten times or until a fine spray appears. The pump may be stored unused for up to 1 week without repriming.

Repriming (as needed)

If unused for more than 1 week, reprime by actuating two times, or until a fine spray appears.

2.2 Recommended Dosage for Prophylaxis of Seasonal Allergic Rhinitis

The recommended dosage for prophylaxis treatment of nasal symptoms of seasonal allergic rhinitis in adult and pediatric patients 12 years and older is mometasone furoate nasal spray 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril once daily (total daily dose of 200 mcg).

In patients with a known seasonal allergen that precipitates nasal symptoms of seasonal allergic rhinitis, prophylaxis with 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril once daily (total daily dose of 200 mcg) is recommended 2 to 4 weeks prior to the anticipated start of the pollen season.

2.3 Recommended Dosage for Treatment of Chronic Rhinosinusitis with Nasal Polyps

The recommended dosage for the treatment of chronic rhinosinusitis with nasal polyps in adults 18 years and older is mometasone furoate nasal spray 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril twice daily (total daily dose of 400 mcg). A dose of 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril once daily (total daily dose of 200 mcg) is also effective in some patients.

5.1 Local Nasal Adverse Reactions

5.2 Glaucoma and Cataracts

Glaucoma and cataracts may be reported with systemic and topical (including nasal, inhaled and ophthalmic) corticosteroid use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use mometasone furoate nasal spray long term [see Adverse Reactions (6)].

5.3 Hypersensitivity Reactions

Hypersensitivity reactions including instances of wheezing may occur after the nasal administration of mometasone furoate monohydrate. Discontinue mometasone furoate nasal spray if such reactions occur [see Contraindications (4)].

5.4 Immunosuppression and Risk of Infections

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective Prescribing Information for VZIG and IG.) If chickenpox develops, treatment with antiviral agents may be considered.

Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infection of the respiratory tract, or in untreated fungal, bacterial, systemic viral infections, or ocular herpes simplex because of the potential for worsening of these infections.

5.5 Hypercorticism and Adrenal Suppression

5.6 Effect on Growth

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

6.1 Clinical Trials Experience

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.

6.2 Post-Marketing Experience

The following adverse reactions have been identified during the post-marketing period for mometasone furoate nasal spray: nasal burning and irritation, anaphylaxis and angioedema, disturbances in taste and smell, nasal septal perforation, and vision blurred. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Inhibitors of Cytochrome P450 3A4: Studies have shown that mometasone furoate is primarily and extensively metabolized in the liver of all species investigated and undergoes extensive metabolism to multiple metabolites. In vitro studies have confirmed the primary role of cytochrome CYP 3A4 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 mometasone furoate nasal spray with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Clinical Pharmacology (12.3)]. 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.

8.1 Pregnancy

8.2 Lactation

Risk Summary

There are no available data on the presence of mometasone furoate nasal spray 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 mometasone furoate nasal spray and any potential adverse effects on the breastfed infant from mometasone furoate nasal spray or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of mometasone furoate nasal spray 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 mometasone furoate nasal spray forthis 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 mometasone furoate nasal spray 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 mometasone furoate nasal spray 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 mometasone furoate nasal spray 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 mometasone furoate nasal spray 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 of 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 mometasone furoate nasal spray, 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 mometasone furoate nasal spray, each patient should be titrated to his/her lowest effective dose.

A clinical study to assess the effect of mometasone furoate nasal spray (100 mcg total daily dose) on growth velocity has been conducted in pediatric patients 3 to 9 years of age with allergic rhinitis. No statistically significant effect on growth velocity was observed for mometasone furoate nasal spray compared to placebo following one year of treatment. No evidence of clinically relevant HPA axis suppression was observed following a 30-minute cosyntropin infusion.

The potential of mometasone furoate nasal spray to cause growth suppression in susceptible patients or when given at higher doses cannot be ruled out.

8.5 Geriatric Use

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 mometasone furoate nasal spray for up to 3 or 4 months, respectively. No observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.

8.6 Hepatic Impairment

Concentrations of mometasone furoate appear to increase with severity of hepatic impairment [see Clinical Pharmacology (12.3)].

12.1 Mechanism of Action

Mometasone furoate nasal spray is a corticosteroid demonstrating potent anti-inflammatory properties. The precise mechanism of corticosteroid action on allergic rhinitis is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation.

In two clinical studies utilizing nasal antigen challenge, mometasone furoate nasal spray decreased some markers of the early- and late-phase allergic response. These observations included decreases (vs. placebo) in histamine and eosinophil cationic protein levels, and reductions (vs. baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins. The clinical significance of these findings is not known.

The effect of mometasone furoate nasal spray on nasal mucosa following 12 months of treatment was examined in 46 patients with allergic rhinitis. There was no evidence of atrophy and there was a marked reduction in intraepithelial eosinophilia and inflammatory cell infiltration (e.g., eosinophils, lymphocytes, monocytes, neutrophils, and plasma cells).

12.2 Pharmacodynamics

Adrenal Function in Adults: Four clinical pharmacology studies have been conducted in humans to assess the effect of mometasone furoate nasal spray at various doses on adrenal function. In one study, daily doses of 200 and 400 mcg of mometasone furoate nasal spray and 10 mg of prednisone were compared to placebo in 64 patients (22 to 44 years of age) with allergic rhinitis. Adrenal function before and after 36 consecutive days of treatment was assessed by measuring plasma cortisol levels following a 6-hour Cortrosyn (ACTH) infusion and by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both the 200- and 400-mcg dose, was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. A statistically significant decrease in the measn plasma cortisol levels post-Cortrosyn infusion and 24-hour urinary free cortisol levels was detected in the prednisone treatment group compared to placebo.

A second study assessed adrenal response to mometasone furoate nasal spray (400 and 1600 mcg/day), prednisone (10 mg/day), and placebo, administered for 29 days in 48 male volunteers (21 to 40 years of age). The 24-hour plasma cortisol area under the curve (AUC0–24), during and after an 8-hour Cortrosyn infusion and 24-hour urinary free cortisol levels were determined at baseline and after 29 days of treatment. No statistically significant differences in adrenal function were observed with mometasone furoate nasal spray compared to placebo.

A third study evaluated single, rising doses of mometasone furoate nasal spray (1000, 2000, and 4000 mcg/day), orally administered mometasone furoate (2000, 4000, and 8000 mcg/day), orally administered dexamethasone (200, 400, and 800 mcg/day), and placebo (administered at the end of each series of doses) in 24 male volunteers (22 to 39 years of age). Dose administrations were separated by at least 72 hours. Determination of serial plasma cortisol levels at 8 AM and for the 24-hour period following each treatment were used to calculate the plasma cortisol area under the curve (AUC0–24). In addition, 24-hour urinary free cortisol levels were collected prior to initial treatment administration and during the period immediately following each dose. No statistically significant decreases in the plasma cortisol AUC, 8 AM cortisol levels, or 24-hour urinary free cortisol levels were observed in volunteers treated with either mometasone furoate nasal spray or oral mometasone, as compared with placebo treatment. Conversely, nearly all volunteers treated with the three doses of dexamethasone demonstrated abnormal 8 AM cortisol levels (defined as a cortisol level <10 mcg/dL), reduced 24-hour plasma AUC values, and decreased 24-hour urinary free cortisol levels, as compared to placebo treatment.

In a fourth study, adrenal function was assessed in 213 patients (18 to 81 years of age) with chronic rhinosinusitis with nasal polyps before and after 4 months of treatment with either mometasone furoate nasal spray (200 mcg once or twice daily) or placebo by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both doses (200 and 400 mcg/day), was not associated with statistically significant decreases in the 24-hour urinary free cortisol levels compared to placebo.

Three clinical pharmacology studies have been conducted in pediatric patients to assess the effect of mometasone furoate nasal spray on the adrenal function at daily doses of 50, 100, and 200 mcg vs. placebo. In one study, adrenal function before and after 7 consecutive days of treatment was assessed in 48 pediatric patients with allergic rhinitis (ages 6 to 11 years) by measuring morning plasma cortisol and 24-hour urinary free cortisol levels. Mometasone furoate nasal spray, at all three doses, was not associated with a statistically significant decrease in mean plasma cortisol levels or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. In the second study, adrenal function before and after 14 consecutive days of treatment was assessed in 48 pediatric patients (ages 3 to 5 years) with allergic rhinitis by measuring plasma cortisol levels following a 30-minute Cortrosyn infusion. Mometasone furoate nasal spray, 50 mcg, at all three doses (50, 100, and 200 mcg/day), was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion compared to placebo. All patients had a normal response to Cortrosyn. In the third study, adrenal function before and after up to 42 consecutive days of once-daily treatment was assessed in 52 patients with allergic rhinitis (ages 2 to 5 years), 28 of whom received mometasone furoate nasal spray, 50 mcg per nostril (total daily dose 100 mcg), by measuring morning plasma cortisol and 24-hour urinary free cortisol levels. Mometasone furoate nasal spray was not associated with a statistically significant decrease in mean plasma cortisol levels or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo.

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 1 and 2 times the maximum recommended daily nasal dose [MRDID] in adults [400 mcg] and children [100 mcg], respectively, on a mcg/m2 basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 2 times the MRDID in adults and children, respectively, on a mcg/m2 basis).

Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary-cell assay, but did not increase chromosomal aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse-lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay and a rat bone marrow chromosomal aberration assay or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes.

In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (less than the MRDID in adults on a mcg/m2 basis).

13.2 Animal Toxicology and/or Pharmacology

14.1 Prophylaxis of Seasonal Allergic Rhinitis in Adult and Pediatric Patients 12 Years of Age and Older

The efficacy and safety of mometasone furoate nasal spray in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis have been evaluated in 18 controlled trials, and one uncontrolled clinical trial, in approximately 3000 adults (ages 17 to 85 years) and pediatric patients (ages 12 to 16 years). Of the total number of patients, there were 1757 males and 1453 females, including a total of 283 adolescents (182 boys and 101 girls) with seasonal allergic or perennial allergic rhinitis. Patients were treated with mometasone furoate nasal spray at doses ranging from 50 to 800 mcg/day. The majority of patients were treated with 200 mcg/day. The allergic rhinitis trials evaluated the total nasal symptom scores that included stuffiness, rhinorrhea, itching, and sneezing. Patients treated with mometasone furoate nasal spray 200 mcg/day had a statistically significant decrease in total nasal symptom scores compared to placebo-treated patients. No additional benefit was observed for mometasone furoate doses greater than 200 mcg/day. A total of 350 patients have been treated with mometasone furoate nasal spray for 1 year or longer.

Prophylaxis of seasonal allergic rhinitis for patients 12 years of age and older with mometasone furoate nasal spray given at a dose of 200 mcg/day, was evaluated in two clinical studies in 284 patients. These studies were designed such that patients received 4 weeks of prophylaxis with mometasone furoate nasal spray prior to the anticipated onset of the pollen season; however, some patients received only 2 to 3 weeks of prophylaxis. Patients receiving 2 to 4 weeks of prophylaxis with mometasone furoate nasal spray demonstrated a statistically significantly smaller mean increase in total nasal symptom scores with onset of the pollen season as compared to placebo patients.

14.2 Chronic Rhinosinusitis with Nasal Polyps in Adults 18 Years of Age and Older

Two studies were performed to evaluate the efficacy and safety of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis with nasal polyps. These studies involved 664 patients with chronic rhinosinusitis with nasal polyps, 441 of whom received mometasone furoate nasal spray. These studies were randomized, double-blind, placebo-controlled, parallel-group, multicenter studies in patients 18 to 86 years of age with bilateral nasal polyps. Patients were randomized to receive mometasone furoate nasal spray 200 mcg once daily, 200 mcg twice daily or placebo for a period of 4 months. The co-primary efficacy endpoints were 1) change from baseline in nasal congestion/obstruction averaged over the first month of treatment; and 2) change from baseline to last assessment in bilateral polyp grade during the entire 4 months of treatment as assessed by 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 (see Table 2 below).

Table 2: Effect of Mometasone Furoate Nasal Spray in Two Randomized, Placebo-Controlled Trials in Patients with Chronic Rhinosinusitis with Nasal Polyps

* polyps in each nasal fossa were graded by the investigator based on endoscopic visualization, using a scale of 0-3 where 0=no polyps; 1=polyps in the middle meatus, not reaching below the inferior border of the middle turbinate; 2=polyps reaching below the inferior border of the middle turbinate but not the inferior border of the inferior turbinate; 3=polyps reaching to or below the border of the inferior turbinate, or polyps medial to the middle turbinate (score reflects sum of left and right nasal fossa grades).

†nasal congestion/obstruction was scored daily by the patient using a 0-3 categorical scale where 0=no symptoms, 1=mild symptoms, 2=moderate symptoms and 3=severe symptoms.

There were no clinically relevant differences in the effectiveness of mometasone furoate nasal spray in the studies evaluating treatment of chronic rhinosinusitis with nasal polyps across subgroups of patients defined by gender, age, or race.

Mometasone Furoate Nasal Spray:

• 50 mcg mometasone furoate per spray
• is supplied in a white, high-density, polyethylene bottle fitted with a white metered-dose, manual spray pump, and translucent cap
• contains 17 g of product formulation (NDC 60505-0830-1)
• 120 sprays, each delivering 50 mcg of mometasone furoate per actuation

Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light.

When mometasone furoate nasal spray is removed from its cardboard container, prolonged exposure of the product to direct light should be avoided. Brief exposure to light, as with normal use, is acceptable.

SHAKE WELL BEFORE EACH USE.

Local Nasal Adverse Reactions

Patients should be informed that treatment with mometasone furoate nasal spray 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 mometasone furoate nasal spray 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 mometasone furoate nasal spray 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 mometasone furoate nasal spray 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.