Sinuva

5 WARNINGS AND PRECAUTIONS Monitor nasal mucosa adjacent to the SINUVA Sinus Implant for any signs of bleeding (epistaxis), irritation, infection, or perforation. Avoid use in patients with nasal ulcers or trauma. ( 5.1 ) Monitor patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts closely. ( 5.2 ) Hypersensitivity reactions, including rash, pruritus, and angioedema, have been reported with use of corticosteroids. ( 5.3 ) Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections. ( 5.4 ) If corticosteroid effects such as hypercorticism and adrenal suppression appear in patients, consider sinus implant removal. ( 5.5 ) 5.1 Local Nasal Adverse Reactions Monitor nasal mucosa adjacent to the SINUVA Sinus Implant for any signs of bleeding (epistaxis), irritation, infection, or perforation. Avoid use in patients with nasal ulcers or trauma. 5.2 Glaucoma and Cataracts Nasal steroids may result in development of glaucoma and/or cataracts. Glaucoma, cataracts, and clinically significant elevation of intraocular pressure were not observed in patients from the treatment group of one randomized controlled clinical study (N = 53) who underwent bilateral placement of SINUVA Sinus Implants. Close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. 5.3 Hypersensitivity Reactions Hypersensitivity reactions, including rash, pruritus, and angioedema have been reported with use of corticosteroids. 5.4 Immunosuppression and Risk of Infections Persons who are using drugs that suppress the immune system, such as corticosteroids, including SINUVA Sinus Implant 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 safety and effectiveness of SINUVA Sinus Implant have not been established in pediatric patients less than 18 years of age and SINVA is not indicated for use in this population. 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 tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. 5.5 Hypercorticism and Adrenal Suppression Hypercorticism and adrenal suppression were not evaluated as part of the SINUVA Sinus Implant clinical program. Since individual sensitivity to effects of cortisol production exists, physicians should consider this information when prescribing SINUVA Sinus Implant. 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 may appear in patients, particularly when systemic mometasone furoate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, consider sinus implant removal.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Local Nasal Adverse Reactions [see Warnings and Precautions (5.1) ] Glaucoma and Cataracts [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Immunosuppression and Risk of Infections [see Warnings and Precautions (5.4) ] Hypercorticism and Adrenal Suppression [see Warnings and Precautions (5.5) ] The most common adverse reactions (in more than 1% of subjects) were bronchitis, nasopharyngitis, otitis media, headache, presyncope, asthma, and epistaxis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Intersect ENT at 1-866 531-6004 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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. The safety of the SINUVA Sinus Implant was evaluated and demonstrated in 400 patients in 2 controlled, randomized, parallel group, single-blind studies. In Study 1, one-hundred (100) subjects were followed for 6 months. In Study 2, three-hundred (300) subjects were followed for 90 days. Of the 400 patients, 254 were assigned to the treatment group and underwent bilateral placement of SINUVA Sinus Implants in the ethmoid sinuses, totaling 2700 mcg of mometasone furoate, and 146 patients were assigned to the control group and underwent a sham procedure consisting of advancement of the Delivery System with the SINUVA Sinus Implant followed by removal without deployment. The Implants were removed by Day 60. All patients were required to use mometasone furoate nasal spray once daily (200 mcg of mometasone furoate) through Day 90. Table 1 shows the common adverse reactions (in greater than 1% of subjects) that occurred more frequently in patients treated with SINUVA Sinus Implant compared to the control group. Table 1: Adverse Reactions with > 1% Incidence and More Common than Control in 90-Day Controlled Clinical Trials with SINUVA Sinus Implant Study 1 & Study 2 Combined Data Adverse Reaction Treatment Patients in the treatment group received SINUVA Sinus Implants placed bilaterally in the ethmoid sinuses and used mometasone furoate nasal spray once daily (200 mcg mometasone furoate) through Day 90. (N = 254) n (%) Control Patients in the control group underwent a sham procedure and used mometasone furoate nasal spray once daily (200 mcg mometasone furoate) through Day 90. (N = 146) n (%) Values represent patient counts and percentages. A patient reporting more than one adverse event for a particular MedDRA preferred term is counted only once. Asthma 12 (4.7) 6 (4.1) Headache 9 (3.5) 5 (3.4) Epistaxis 6 (2.4) 2 (1.4) Presyncope 6 (2.4) 3 (2.1) Bronchitis 5 (2.0) 2 (1.4) Otitis media 5 (2.0) 2 (1.4) Nasopharyngitis 3 (1.2) 1 (0.7) Study 1 monitored patients from Day 90 through 6 months. Hypersensitivity (4% (n=2) vs. 0), chronic rhinosinusitis (11% (n=6) vs. 9% (n=4)), and upper respiratory tract infections (8% (n=4) vs. 2% (n=1)) were reported in more than 2 subjects in the treatment group, and more commonly than the control group during this time period. The safety of repeat administration of the SINUVA Sinus Implant was evaluated in Study 3 that was an open-label, single-arm, multicenter study in 50 patients. All patients underwent an in- office bilateral placement of the SINUVA Sinus Implant in each ethmoid sinus (totaling 2 implants) and were followed for 365 days. Patients were required to use mometasone furoate nasal spray once daily (200 mcg of mometasone furoate) through 365 days. At 90 days, the remaining implants were removed. To maximize the size of the safety population, patients with ethmoid sinus polyps grade ≥ 1 on any side were considered for repeat implant placement. Repeat placement was not performed if polyp grade was < 1, or if the patient declined it. Of the 50 patients, 41 received repeat implant placement (33 bilaterally and 8 unilaterally). Acute sinusitis (29%, n=12), upper respiratory infection (17%, n=7) epistaxis (12%, n=5), nasal discomfort or rhinalgia (12%, n=5), headache (7%, n=3), were the common adverse reactions that occurred in at least 3 subjects who underwent repeat placement during the study period. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of the SINUVA sinus implant. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to SINUVA, or a combination of these factors, include: implant migration, lack of efficacy, nasal pain, headache, epistaxis. 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 experience.

<table width="75%" ID="Table1"><caption>Table 1: Adverse Reactions with &gt; 1% Incidence and More Common than Control in 90-Day Controlled Clinical Trials with SINUVA Sinus Implant</caption><col width="45%" align="left" valign="bottom"/><col width="30%" align="center" valign="bottom"/><col width="25%" align="center" valign="bottom"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule Botrule" colspan="2">Study 1 &amp; Study 2 Combined Data</th></tr><tr><th styleCode="Lrule Rrule" align="center">Adverse Reaction</th><th styleCode="Rrule">Treatment <footnote>Patients in the treatment group received SINUVA Sinus Implants placed bilaterally in the ethmoid sinuses and used mometasone furoate nasal spray once daily (200 mcg mometasone furoate) through Day 90. </footnote> (N = 254) n (%)</th><th styleCode="Rrule">Control <footnote>Patients in the control group underwent a sham procedure and used mometasone furoate nasal spray once daily (200 mcg mometasone furoate) through Day 90. </footnote> (N = 146) n (%)</th></tr></thead><tfoot><tr><td align="left" colspan="3">Values represent patient counts and percentages. A patient reporting more than one adverse event for a particular MedDRA preferred term is counted only once. </td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Asthma</td><td styleCode="Rrule">12 (4.7)</td><td styleCode="Rrule">6 (4.1)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">9 (3.5)</td><td styleCode="Rrule">5 (3.4)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Epistaxis</td><td styleCode="Rrule">6 (2.4)</td><td styleCode="Rrule">2 (1.4)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Presyncope</td><td styleCode="Rrule">6 (2.4)</td><td styleCode="Rrule">3 (2.1)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Bronchitis</td><td styleCode="Rrule">5 (2.0)</td><td styleCode="Rrule">2 (1.4)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Otitis media</td><td styleCode="Rrule">5 (2.0)</td><td styleCode="Rrule">2 (1.4)</td></tr><tr><td styleCode="Lrule Rrule">Nasopharyngitis</td><td styleCode="Rrule">3 (1.2)</td><td styleCode="Rrule">1 (0.7)</td></tr></tbody></table>