MOMETASONE FUROATE: 11,619 Adverse Event Reports & Safety Profile

RYALTRIS is a metered-dose manual nasal spray unit containing an aqueous suspension of a fixed‑dose combination of a histamine-1 (H1) receptor inhibitor (olopatadine hydrochloride) and a corticosteroid (mometasone furoate monohydrate). Olopatadine hydrochloride is a white, sparingly water‑soluble crystalline powder. The chemical name for olopatadine hydrochloride is 2‑[(11Z)-11-[3-(dimethylamino)propylidene]-6H-benzo[c][1]benzoxepin-2-yl]acetic acid hydrochloride. It has a molecular weight of 373.88, and its molecular formula is C 21 H 23 NO 3

• HCl with the following chemical structure: Mometasone furoate monohydrate is an anti-inflammatory corticosteroid having the chemical name [(8S,9R,10S,11S,13S,14S,16R,17R)-9-chloro-17-(2-chloroacetyl)-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] furan-2-carboxylate;hydrate and the following chemical structure: Mometasone furoate monohydrate is a white powder, with an empirical formula of C 27 H 30 C l2 O 6
• H 2 O and a molecular weight of 539.45. It is practically insoluble in water; slightly soluble in methanol, ethanol, and isopropanol; soluble in acetone and chloroform; and freely soluble in tetrahydrofuran. Its partition coefficient between octanol and water is >5000. RYALTRIS is a nasal spray containing an isotonic aqueous suspension of olopatadine hydrochloride (equivalent to 0.6% w/v olopatadine base) and mometasone furoate monohydrate (equivalent to 0.025% w/w mometasone furoate on the anhydrous basis). After initial priming (6 sprays), each metered spray delivers 100 microliters of suspension containing 665 mcg of olopatadine hydrochloride (equivalent to 600 mcg olopatadine base) and 25 mcg of mometasone furoate. RYALTRIS also contains benzalkonium chloride, carboxymethyl cellulose sodium, dibasic sodium phosphate heptahydrate, edetate disodium, hydrochloric acid, microcrystalline cellulose, polysorbate 80, sodium chloride, sodium hydroxide, and water. It has a pH of approximately 3.7 [see How Supplied/Storage and Handling ( 16 )] . structureolopatadine structuremometasone

AND USAGE Mometasone Furoate Monohydrate Nasal Spray is a corticosteroid indicated for: Prophylaxis of Nasal Symptoms of Seasonal Allergic Rhinitis in adult and pediatric patients 12 years of age and older ( 1.1 ) Treatment of Chronic Rhinosinusitis with Nasal Polyps in adult patients 18 years of age and older ( 1.2 )

1.1 Prophylaxis of Seasonal Allergic Rhinitis Mometasone furoate monohydrate 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 monohydrate nasal spray is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients 18 years of age and older.

AND ADMINISTRATION The SINUVA Sinus Implant is loaded into a Delivery System and placed in the ethmoid sinus under endoscopic visualization.

The

Implant may be left in the sinus to gradually release the corticosteroid over 90 days. Remove the implant by 90 days or earlier at the physician's discretion using standard surgical instruments. ( 2.2 ) To be inserted by physicians trained in otolaryngology. ( 2.3 )

2.1 Recommended Dosage The recommended dosage is one SINUVA Sinus Implant (1350 mcg of mometasone furoate) placed in an ethmoid sinus <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> . The SINUVA Sinus Implant may be left in the sinus to gradually release the corticosteroid over 90 days. Remove the SINUVA Sinus Implant by 90 days or earlier at the physician&apos;s discretion <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> .

2.2 Health Care Provider Training The SINUVA Sinus Implant is to be used by physicians trained in otolaryngology. Specialized training is not required for these physicians .

2.3 Placement of SINUVA Sinus Implant The SINUVA Sinus Implant is designed for single patient use only. Do not reprocess or reuse. Do not use if the package is open, the package or product is damaged, or has evidence of gross contamination. Special care should be taken to avoid bending, twisting, or damaging the implant. The implant is not designed to be modified by the physician. The implant is not intended to be compressed and loaded into the Delivery System more than two times. The implant must be placed under endoscopic visualization.

Patient Preparation

The patient should be prepared following routine protocols for in-office sinonasal endoscopic procedures.

Implant Preparation

The SINUVA Sinus Implant (Figure 1) is loaded into a Delivery System and placed in the ethmoid sinus. Remove the Crimper (Figure 2) and the Delivery System (Figure 3) from their protective packaging using sterile technique. Inspect the SINUVA Sinus Implant located inside of the Crimper (Figure 2). Do not remove the Implant from the Crimper. Prior to use, the SINUVA Sinus Implant must be crimped and loaded into the Delivery System. If the SINUVA Sinus Implant is not fully seated inside of the Crimper, secure the SINUVA Sinus Implant before proceeding. See instructions to secure the SINUVA Sinus Implant (Figure 12–15).

Implant

Length (nominal): 20 mm Expanded Diameter (nominal): 34 mm DELIVERY SYSTEM Shaft Length 117 mm Figure 1: Implant Figure 2: Crimper with Implant Figure 3: Delivery System Place the Crimper on a flat surface and hold to prevent any potential slipping of the Crimper during loading of the SINUVA Sinus Implant into the Delivery System. Orient the Crimper such that the short ends of the Implant are in the 12 o'clock and 6 o'clock position (Figure 4).

Figure

4 Grasp the Delivery System with the index and middle fingers on the left or right hand using the Finger Rests and the thumb in the Thumb Rest (Figure 5).

Figure

5 Pull back on the Finger Rests while pressing down on the Thumb Rest to retract the Cup and expose the Seeker (Figure 6).

Figure

6 Position the tip of the Seeker with its 10° angled tip downwards toward the user in the depression in the center of the SINUVA Sinus Implant (Figure 7). The distal end of the angled shaft must be in a vertical position, perpendicular to the Crimper, during positioning. Ensure the plane of the angled tip is in the same plane as the short ends of the Implant that were oriented in the 12 o'clock / 6 o'clock position in step 1.

Figure

7 With the Thumb Rest depressed, gradually apply perpendicular downward force to the SINUVA Sinus Implant until the ends of the Implant collapse around the Seeker of Delivery System (Figure 8). Make sure that the Finger Rests are not released while pushing downwards.

Figure

8 The SINUVA Sinus Implant should crimp in a radial fashion onto the Seeker. Implant ends should not cross over or past each other when being crimped onto the Seeker by the Crimper. While maintaining steady downward pressure on the Thumb Rest, slowly release the Finger Rests with the index and middle fingers until the Cup lowers and captures all ends of the SINUVA Sinus Implant (Figure 9). If necessary, adjust the position of the Delivery System with slight circular movements, slightly lifting and then lowering the Cup into position to ensure that all eight ends of the SINUVA Sinus Implant are secured within the Cup.

Figure

9 Apply a downward push on the Delivery System to ensure that the SINUVA Sinus Implant is secured in the Cup (Figure 10). This will also ensure the Implant is compressed to its smallest profile for insertion.

Figure

10 Retract the Delivery System from the Crimper. The SINUVA Sinus Implant should remain symmetrically loaded in the Cup of the Delivery System (Figure 11).

Figure

11 CAUTION: Do not leave the SINUVA Sinus Implant in the crimped state for more than 5 minutes prior to placement.

Figure

1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Instructions to Secure the SINUVA Sinus Implant in the Crimper If necessary, the Implant may be reloaded into the Crimper for a second time. CAUTION: The SINUVA Sinus Implant should not be used if the second attempt to crimp is unsuccessful. Hold the SINUVA Sinus Implant by one end as shown in Figure 12.

Figure

12 Holding the SINUVA Sinus Implant with the dome-shaped Cap positioned downward (Figure 13), place the Implant back into the Crimper.

Figure

13 Ensure that each Implant is secured in the Crimper by pressing down on the center of the Implant until all ends of the Implant are below the rim of the Crimper (Figure 14).

Figure

14 Inspect the Implant and the Crimper to ensure that all the Implant ends are secured below the rim of the Crimper (Figure 15). Return to Implant Preparation Step 1 for instructions on how to load the re-secured implant into the delivery system.

Figure

15 Figure 12 Figure 13 Figure 14 Figure 15 Instructions for the SINUVA Sinus Implant Placement Advance the Delivery System under endoscopic visualization into the ethmoid sinus cavity. Ensure that the Delivery System is oriented such that the 10° curvature of the distal tip is curved superiorly. Insert the Delivery System such that the Shaft is parallel to roof of ethmoid sinus. If the SINUVA Sinus Implant becomes dislodged from the Delivery System prior to placement into the ethmoid sinus, remove the Implant and inspect for damage, re-load the undamaged Implant in the Crimper, and re-crimp the Implant into the Delivery System. Note that the SINUVA Sinus Implant should not be loaded into the Delivery System more than twice. Release the SINUVA Sinus Implant by pressing down on the Thumb Rest while pulling back on the Finger Rests in a controlled manner. Place the SINUVA Sinus Implant amongst the sinus polyps with the cap oriented toward the posterior ethmoid sinus, and with the Implant positioned as superiorly as possible in the sinus. The long ends of the Implant should be in approximately the 2 o'clock, 4 o'clock, 8 o'clock and 10 o'clock positions, respectively. Confirm final placement of the SINUVA Sinus Implant by endoscopic visualization. To adjust the position of the SINUVA Sinus Implant, use the Seeker on the Delivery System or standard endoscopic surgical instruments.

Post Placement Instructions

Reposition the Implant if its ends are perpendicular to and in contact with the nasal septum. Avoid excessive manipulation of the Implant during follow-up, as this can cause dislodgement.

2.4 Removal Instructions The SINUVA Sinus Implant is made from bioabsorbable polymers designed to gradually soften over time. Remove the SINUVA Sinus Implant by day 90 or earlier at the physician&apos;s discretion using standard endoscopic instruments.

ASMANEX TWISTHALER is contraindicated: Status Asthmaticus: in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Hypersensitivity: in patients with known hypersensitivity to milk proteins or any ingredients of ASMANEX TWISTHALER [see Warnings and Precautions (5.3) and Description (11) ]. Patients with status asthmaticus or other acute episodes of asthma where intensive measures are required. ( 4 ) Patients with a known hypersensitivity to milk proteins or any ingredients of ASMANEX TWISTHALER. ( 4 )

REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Oropharyngeal Candidiasis [see Warnings and Precautions (5.1) ] Immunosuppression and Risk of Infections [see Warnings and Precautions (5.4) ] Hypercorticism and Adrenal Suppression [see Warnings and Precautions (5.6) ] Reduction in Bone Mineral Density [see Warnings and Precautions (5.7) ]

Growth

Effects [see Warnings and Precautions (5.8) and Use in Specific Populations (8.4) ] Glaucoma and Cataracts [see Warnings and Precautions (5.9) ] The most common adverse reactions (incidence ≥5%) are headache, allergic rhinitis, pharyngitis, upper respiratory tract infection, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, and dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Organon LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Studies Experience The safety data described below reflect exposure to ASMANEX TWISTHALER in 2380 patients with asthma exposed for 8 to 12 weeks and 627 patients with asthma exposed for 1 year in a total of 17 clinical trials. In adult and adolescent patients 12 years of age and older, ASMANEX TWISTHALER was studied in 10 placebo-controlled clinical trials of 8 to 12 weeks duration with a total of 1750 patients receiving ASMANEX TWISTHALER. There were also 3 trials with a total of 475 patients receiving ASMANEX TWISTHALER for 1 year. In the 8- to 12-week clinical trials, the population was 12 to 83 years of age; 38% males and 62% females; and 83% Caucasian, 8% black, 6% Hispanic, and 3% other race/ethnicity. Patients received ASMANEX TWISTHALER 110 mcg twice daily (n=133), 220 mcg once daily in the morning (n=209), 220 mcg once daily in the evening (n=232), 220 mcg twice daily (n=433), 440 mcg once daily in the morning (n=419), 440 mcg once daily in the evening (n=250), or 440 mcg twice daily (n=74).

In

3 long-term safety trials (two 9-month extensions of efficacy trials and one 52-week active-controlled safety trial), 475 patients with asthma (12-83 years of age, 44% males, 56% females, 87% Caucasian, 8% black, 4% Hispanic, and 1% other race/ethnicity) received various doses of ASMANEX TWISTHALER for 1 year. In pediatric patients 4 to 11 years of age, ASMANEX TWISTHALER was studied in 3 placebo-controlled clinical trials of 12 weeks duration with a total of 630 patients receiving ASMANEX TWISTHALER and a 52-week, active-controlled safety trial with a total of 152 patients receiving ASMANEX TWISTHALER. In the 12-week clinical trials, the population was 4 to 11 years of age; 63% males and 37% females; and 67% Caucasian, 13% black, 17% Hispanic, and 3% other race/ethnicity. Patients received ASMANEX TWISTHALER 110 mcg once daily in the evening (n=98), 110 mcg once daily in the morning (n=181), 110 mcg twice daily (n=179), or 220 mcg once daily in the morning (n=172). In the long-term active-controlled safety trial (n=152), patients with asthma (4 to 11 years of age, 60% males and 40% females, 84% Caucasian, 11% Black, and 5% Hispanic) received ASMANEX TWISTHALER 110 mcg twice daily or 220 mcg once daily in the morning for 52 weeks. 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. Adults and Adolescents 12 Years of Age and Older: The safety results of the 10 trials that were 8 to 12 weeks in duration were pooled because patients with asthma in these studies were previously maintained on bronchodilators and/or inhaled corticosteroids. The safety results of the one 12-week clinical trial in patients with asthma previously treated with oral corticosteroids are presented separately. In the pooled 8- to 12-week clinical trials, adverse reactions were reported in 70% of patients treated with ASMANEX TWISTHALER (n=1750) compared to 65% of patients taking placebo (n=720).

Table

2 displays the common adverse reactions (≥3% in any patient group receiving ASMANEX TWISTHALER) that occurred more frequently in patients treated with ASMANEX TWISTHALER compared to patients treated with placebo.

Table

2: Adverse Reactions with ≥3% Incidence in 10 Controlled Clinical Trials with ASMANEX TWISTHALER in Patients 12 Years of Age and Older Previously on Bronchodilators and/or Inhaled Corticosteroids (%) of Patients ASMANEX TWISTHALER Adverse Reaction 220 mcg twice daily (n=433) 440 mcg once daily (n=497) 220 mcg once daily in the evening (n=232) Placebo (n=720)

Headache

22 17 20 20 Allergic Rhinitis 15 11 14 13 Pharyngitis 11 8 13 7 Upper Respiratory Infection 10 8 15 7 Sinusitis 6 6 5 5 Candidiasis, oral 6 4 4 2 Dysmenorrhea Percentages are based on the number of female patients. 9 4 4 4 Musculoskeletal Pain 8 4 4 5 Back Pain 6 3 3 4 Dyspepsia 5 3 3 3 Myalgia 3 2 3 2 Abdominal Pain 3 2 3 2 Nausea 3 1 3 2 Average Duration of Exposure (Days) 81 70 80 62 The following other adverse reactions occurred in these clinical trials with an incidence of at least 1% but less than 3% and were more common on ASMANEX TWISTHALER therapy than on placebo: Body as a Whole: fatigue, flu-like symptoms, pain Gastrointestinal: gastroenteritis, vomiting, anorexia Hearing, Vestibular: earache Resistance Mechanism: infection Respiratory: dysphonia, epistaxis, nasal irritation, respiratory disorder, throat dry In the 12-week trial in adult asthmatics who previously required oral corticosteroids, the effects of ASMANEX TWISTHALER therapy administered as two 220-mcg inhalations twice daily (n=46) were compared with those of placebo (n=43). Adverse reactions, whether considered drug-related or not by the investigators, reported in more than 3 patients in the ASMANEX TWISTHALER treatment group, and which occurred more frequently than in placebo were (ASMANEX TWISTHALER % vs. placebo %): musculoskeletal pain (22% vs. 14%), oral candidiasis (22% vs. 9%), sinusitis (22% vs. 19%), allergic rhinitis (20% vs. 5%), upper respiratory infection (15% vs. 14%), arthralgia (13% vs. 7%), fatigue (13% vs. 2%), depression (11% vs. 0%), and sinus congestion (9% vs. 0%). In considering these data, an increased duration of exposure for patients on ASMANEX TWISTHALER treatment (77 days vs. 58 days on placebo) should be taken into account. Long-Term Clinical Trials Experience - 12 Years of Age and Older: In 3 long-term safety trials, 475 patients with asthma 12 years of age and older were treated with ASMANEX TWISTHALER 220 mcg twice daily (n=60), 220 mcg once daily in the morning (n=41), 220 mcg once daily in the evening (n=40), 440 mcg once daily in the morning (n=44), 440 mcg once daily in the evening (n=41), 440 mcg twice daily (n=62), 880 mcg once daily (n=59), or at variable doses (n=128) for 52 weeks. The safety profile of ASMANEX TWISTHALER in the 52-week trials was similar to the findings in the 8- to 12-week clinical trials. In patients previously on inhaled corticosteroids, cataracts were reported in 3 patients (0.9%) treated with ASMANEX TWISTHALER, compared to 1 patient (1.7%) treated with the active comparator medication. Increased ocular pressure at the end of the study was observed in 2 patients, both on ASMANEX TWISTHALER 880 mcg once daily in the morning. Oral candidiasis, dysphonia, and dysmenorrhea were seen at a higher frequency with long-term administration than in the 8- to 12-week trials.

Pediatric Patients

4 to 11 Years of Age: In the three 12-week clinical trials in pediatric patients 4 to 11 years of age, patients with asthma were previously maintained on bronchodilators and/or inhaled corticosteroids. The safety results from 1 trial are described in Table 3 for ASMANEX TWISTHALER 110 mcg once daily in the evening. The safety results from the other 2 trials showed similar findings. Overall adverse reactions were reported with approximately the same frequency by patients treated with ASMANEX TWISTHALER and those receiving placebo.

Table

3 displays the common adverse reactions (≥2% in any patient group receiving ASMANEX TWISTHALER) that occurred more frequently in patients 4 to 11 years of age treated with ASMANEX TWISTHALER compared with placebo-treated patients.

Table

3: Adverse Reactions with ≥2% Incidence in a 12-Week Study with ASMANEX TWISTHALER in Patients 4 to 11 Years of Age Previously on Bronchodilators and/or Inhaled Corticosteroids (%) of Patients ASMANEX TWISTHALER Adverse Reaction 110 mcg once daily in the evening (n=98) Placebo (n=99)

Fever

7 5 Allergic Rhinitis 4 3 Abdominal Pain 6 2 Vomiting 3 2 Urinary Tract Infection 2 1 Bruise 2 0 Average Duration of Exposure (Days) 72 68 Long-Term Clinical Trials Experience in Children 4 to 11 Years of Age: In a 52-week, active-controlled, long-term safety trial, 152 patients with asthma 4 to 11 years of age were treated with ASMANEX TWISTHALER 110 mcg twice daily (n=74) or 220 mcg once daily (n=78). The safety profile for ASMANEX TWISTHALER in the 52-week trial was similar to the findings in the 12-week clinical trials.

6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of ASMANEX TWISTHALER. Because they 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. Eye disorders: Vision blurred <span class="opacity-50 text-xs">[see Warnings and Precautions (5.9) ]</span> .

Immune System

Disorders: Immediate and delayed hypersensitivity reactions including rash, pruritus, angioedema and anaphylactic reaction [see Warnings and Precautions (5.3) and Contraindications (4) ] . Respiratory, Thoracic and Mediastinal Disorders: Asthma aggravation, which may include cough, dyspnea, wheezing and bronchospasm.

AND PRECAUTIONS Deterioration of asthma and acute episodes: ASMANEX HFA should not be used for relief of acute symptoms. Patients require immediate re-evaluation during rapidly deteriorating asthma. ( 5.1 ) Localized infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. After dosing, advise patients to rinse their mouth with water and spit out contents without swallowing. ( 5.2 ) Immunosuppression: Potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Use with caution in patients with these infections because of the potential for worsening of these infections. ( 5.3 ) Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids. Wean patients slowly from systemic corticosteroids if transferring to ASMANEX HFA. ( 5.4 ) Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue ASMANEX HFA slowly. ( 5.5 ) Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. Exercise caution when used with ASMANEX HFA. ( 5.6 ) Paradoxical bronchospasm: Discontinue ASMANEX HFA and institute alternative therapy if paradoxical bronchospasm occurs. ( 5.7 ) Hypersensitivity reactions including anaphylaxis: Hypersensitivity reactions, such as urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reaction may occur. Discontinue ASMANEX HFA if such reactions occur. ( 5.8 ) Decreases in bone mineral density: Monitor patients with major risk factors for decreased bone mineral content. ( 5.9 ) Effects on growth: Monitor growth of pediatric patients. ( 5.10 ) Glaucoma and cataracts: Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX HFA long term. ( 5.11 )

5.1 Deterioration of Asthma and Acute Episodes ASMANEX HFA is not indicated for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta 2 -agonist, not ASMANEX HFA, should be used to relieve acute symptoms such as shortness of breath. When prescribing ASMANEX HFA, the physician must also provide the patient with an inhaled, short-acting beta 2 -agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily (morning and evening) use of ASMANEX HFA. Instruct patients to contact their physician immediately if episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with ASMANEX HFA. During such episodes, patients may require therapy with oral corticosteroids.

5.2 Local Effects In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans have occurred in patients treated with ASMANEX HFA. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while remaining on treatment with ASMANEX HFA therapy, but at times therapy with ASMANEX HFA may need to be interrupted. To reduce the risk of oropharyngeal candidiasis, after dosing with ASMANEX HFA, advise patients to rinse their mouth with water and spit out the contents without swallowing.

5.3 Immunosuppression Persons who are using drugs that 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 susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or who are not properly immunized, 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) or pooled intravenous immunoglobulin (IVIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

5.4 Transferring Patients from Systemic Corticosteroid Therapy Particular care is needed for patients who are transferred from systemically active corticosteroids to ASMANEX HFA because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although ASMANEX HFA may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity necessary for coping with these emergencies. During periods of stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe asthma attack. Patients requiring oral or other systemic corticosteroids should be weaned slowly from oral or other systemic corticosteroid use after transferring to ASMANEX HFA. Lung function (FEV 1 or PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral or other systemic corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to ASMANEX HFA may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function.

5.5 Hypercorticism and Adrenal Suppression ASMANEX HFA will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since mometasone furoate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of ASMANEX HFA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with ASMANEX HFA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients, particularly when mometasone furoate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of ASMANEX HFA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms.

5.6 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of ASMANEX HFA with ketoconazole, and other known strong cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to mometasone furoate may occur <span class="opacity-50 text-xs">[see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]</span>.

5.7 Paradoxical Bronchospasm and Upper Airway Symptoms ASMANEX HFA may produce inhalation induced bronchospasm with an immediate increase in wheezing after dosing that may be life-threatening. If inhalation induced bronchospasm occurs, it should be treated immediately with an inhaled, short-acting bronchodilator. ASMANEX HFA should be discontinued immediately and alternative therapy instituted.

5.8 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions such as urticaria, flushing, allergic dermatitis, and bronchospasm, may occur after administration of ASMANEX HFA. Discontinue ASMANEX HFA if such reactions occur <span class="opacity-50 text-xs">[see Contraindications (4.2) ]</span>. The following additional hypersensitivity reactions, such as rash, pruritus, angioedema, and anaphylactic reaction, have been reported after administration of mometasone furoate dry powder inhaler (DPI) <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span>.

5.9 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including mometasone furoate. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care. In a 2-year double-blind study in 103 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (Baseline FEV 1 85%-88% predicted), treatment with mometasone furoate dry powder inhaler 200 mcg twice daily resulted in significant reductions in lumbar spine (LS) BMD at the end of the treatment period compared to placebo. The mean change from Baseline to Endpoint in the lumbar spine BMD was -0.015 (-1.43%) for the mometasone furoate dry powder inhaler group compared to 0.002 (0.25%) for the placebo group. In another 2-year double-blind study in 87 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (Baseline FEV 1 82%-83% predicted), treatment with mometasone furoate dry powder inhaler 400 mcg twice daily demonstrated no statistically significant changes in lumbar spine BMD at the end of the treatment period compared to placebo. The mean change from Baseline to Endpoint in the lumbar spine BMD was -0.018 (-1.57%) for the mometasone furoate group compared to -0.006 (-0.43%) for the placebo group.

5.10 Effect on Growth Orally inhaled corticosteroids, including ASMANEX HFA, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving ASMANEX HFA routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ASMANEX HFA, titrate each patient&apos;s dose to the lowest dosage that effectively controls his/her symptoms <span class="opacity-50 text-xs">[see Use in Specific Populations (8.4) ]</span> .

5.11 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported following the use of long-term administration of inhaled corticosteroids, including mometasone furoate. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX HFA long term <span class="opacity-50 text-xs">[see Adverse Reactions (6) ]</span> .

INTERACTIONS In clinical trials, concurrent administration of ASMANEX HFA and other drugs, such as short-acting beta 2 -agonist and intranasal corticosteroids have not resulted in an increased frequency of adverse drug reactions. No formal drug interaction studies have been performed with ASMANEX HFA. Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects. ( 7.1 )

7.1 Inhibitors of Cytochrome P450 3A4 The main route of metabolism of corticosteroids, including mometasone furoate, is via CYP3A4. After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally inhaled mometasone furoate increased. 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 ASMANEX HFA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) <span class="opacity-50 text-xs">[see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) ]</span> . 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.

Active ingredient (in each spray) Mometasone furoate monohydrate (glucocorticoid) 50 mcg

Inactive ingredients benzalkonium chloride, citric acid monohydrate, glycerin, microcrystalline cellulose and carboxymethylcellulose sodium, polysorbate 80, purified water, sodium citrate (dihydrate)