Sinuva Drug Information

Sinus Implant is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients ≥18 years of age who have had ethmoid sinus surgery. SINUVA Sinus Implant is a corticosteroid-eluting implant indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients ≥ 18years of age who have had ethmoid sinus surgery.

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 subjects were followed for 6 months.

In Study 2, three-hundred 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 6 Headache 9 5 Epistaxis 6 2 Presyncope 6 3 Bronchitis 5 2 Otitis media 5 2 Nasopharyngitis 3 1 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.

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.

Inhibitors of Cytochrome P450 3A4 Co-administration with ketoconazole, a potent

CYP 3A4 inhibitor, may increase the plasma concentrations of mometasone furoate .

Pregnancy Risk Summary There are no randomized clinical studies of SINUVA Sinus Implant or mometasone furoate in pregnant women. The active pharmaceutical ingredient, mometasone furoate is systemically available when administered topically or when inhaled. In animal reproduction studies, subcutaneous administration of mometasone furoate to pregnant mice, rats, or rabbits 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/m 2 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. 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 an exposure approximately one-third of the MRHD (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at an exposure approximately equivalent to the MRHD (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure approximately one-tenth of the MRHD (on a mcg/m 2 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 6 times the MRHD (on a mcg/m2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at exposures approximately 3 times the MRHD (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 an exposure that was approximately 8 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings with an exposure approximately 4 times the MRHD (on an AUC 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 an exposure approximately 3 times the MRHD (on a mcg/m 2 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 an exposure approximately 1/2 of the MRHD (on AUC basis with a maternal oral dose of 700 mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis with a maternal oral dose of 140 mcg/kg).

Pediatric Use The safety and effectiveness of the SINUVA Sinus Implant have not been established in pediatric patients less than 18 years of age.

Patients with known hypersensitivity to mometasone furoate, or to any of the copolymers of the SINUVA Sinus Implant . Patients with known hypersensitivity to mometasone furoate and any of the ingredients of the SINUVA Sinus Implant.

There are no data available on the effects of acute or chronic overdosage with SINUVA Sinus Implant. Chronic overdosage may result in signs/symptoms of hypercorticism .