PATANASE NASAL SPRAY SIDE EFFECTS

SIDE EFFECTS

The most clinically significant adverse reactions described in other sections of labeling include:

• Epistaxis, Nasal Ulceration, and Nasal Septal Perforation
• Somnolence and Impaired Mental Alertness

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 data described below reflect exposure to PATANASE in 2770 patients with seasonal or perennial allergic rhinitis in 10 controlled clinical trials of 2 weeks to 12 months duration. PATANASE is not indicated for use in patients with perennial allergic rhinitis.

The safety data from adults and adolescents are based upon 6 placebo-controlled clinical trials (3.7 pH vehicle nasal spray or 7.0 pH vehicle nasal spray) in which 1834 patients with seasonal or perennial allergic rhinitis (652 males and 1182 females) 12 years of age and older were treated with PATANASE two sprays per nostril twice daily. There were 1180 patients (PATANASE, 587; vehicle nasal spray, 593) that participated in 3 efficacy and safety trials of 2 weeks duration. There were 2840 patients (PATANASE, 1247; 3.7 pH vehicle nasal spray, 1251; 7.0 pH vehicle nasal spray, 342) that participated in 3 long-term clinical trials of 1-year duration. The racial distribution of adult and adolescent patients receiving PATANASE was 77% white, 9% black, and 14% other. The incidence of discontinuation due to adverse reactions in these controlled clinical trials was comparable for PATANASE and vehicle nasal spray. Overall, 4.7% of the 1834 adult and adolescent patients across all 6 studies treated with PATANASE, 3.5% of the 1844 patients treated with 3.7 pH vehicle nasal spray discontinued due to adverse reactions, and 2.9% of the 342 patients treated with 7.0 pH vehicle nasal spray discontinued due to adverse reactions.

The safety data from pediatric patients 6 to 11 years of age are based upon 3 clinical trials in which 870 children with SAR (376 females and 494 males) were treated with PATANASE one or two sprays per nostril twice daily for 2 weeks. The racial distribution of pediatric patients receiving PATANASE was 68.6% white, 16.6% black, and 14.8% other. The incidence of discontinuation due to adverse reactions in these controlled clinical trials was comparable for PATANASE and vehicle nasal spray. Overall, 1.4% of the 870 pediatric patients across all 3 studies treated with PATANASE and 1.3% of the 872 pediatric patients treated with vehicle nasal spray discontinued due to adverse reactions.

Adults And Adolescents 12 Years Of Age And Older In Short-Term (2 week) Trials

There were 1180 patients 12 years of age and older (PATANASE, 587; vehicle nasal spray, 593) that participated in 3 efficacy and safety trials of 2 weeks duration. Table 1 presents the most common adverse reactions (0.9% or greater in patients treated with PATANASE) that occurred more frequently in patients treated with PATANASE compared with vehicle nasal spray in the 3 clinical trials of 2 weeks duration.

Table 1: Adverse Reactions Occurring at an Incidence of 0.9% or Greater in Controlled Clinical Trials of 2 Weeks Duration With PATANASE in Adolescent and Adult Patients 12 Years of Age and Older With Seasonal Allergic Rhinitis

There were no differences in the incidence of adverse reactions based on gender or race. Clinical trials did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger subjects.

Pediatric Patients 6 To 11 Years Of Age

There were 1742 pediatric patients 6 to 11 years of age (olopatadine nasal spray, 870; vehicle nasal spray, 872) with SAR that participated in 3 clinical trials of 2 weeks duration. Two of the studies used the investigational formulation of olopatadine nasal spray, and one of the studies used PATANASE. One study evaluated the safety of PATANASE at doses of one and two sprays per nostril twice daily in 1188 patients, in which 298 were exposed to PATANASE 1 spray, 296 were exposed to PATANASE 2 sprays, 297 were exposed to vehicle 1 spray, and 297 were exposed to vehicle 2 sprays twice daily for 2 weeks. Table 2 presents the most common adverse reactions (greater than 1.0% in pediatric patients 6 to 11 years of age treated with PATANASE one spray per nostril) that occurred more frequently with PATANASE compared with vehicle nasal spray.

Table 2: Adverse Reactions Occurring at an Incidence of Greater Than 1.0% in a Controlled Clinical Trial of 2 Weeks Duration With PATANASE in Pediatric Patients 6 to 11 Years of Age With Seasonal Allergic Rhinitis

There were no differences in the incidence of adverse reactions based on gender, race, or ethnicity.

Long-Term (12 month) Safety Trials

In a 12-month, placebo-controlled, safety trial (vehicle nasal spray), 890 patients 12 years of age and older with perennial allergic rhinitis were randomized to treatment with PATANASE two sprays per nostril twice daily (445 patients) or vehicle nasal spray (445 patients). In the PATANASE and vehicle nasal spray groups, 72% and 74% of patients, respectively, completed the trial. Overall, 7% and 5%, respectively, discontinued study participation due to an adverse reaction. The most frequently reported adverse reaction was epistaxis, which occurred in 25% of patients treated with PATANASE and 28% in patients treated with vehicle nasal spray. Epistaxis resulted in discontinuation of 0.9% of patients treated with PATANASE and 0.2% of patients treated with vehicle nasal spray. Nasal ulcerations occurred in 10% of patients treated with PATANASE and 9% of patients treated with vehicle nasal spray. Nasal ulcerations resulted in discontinuation of 0.4% of patients treated with PATANASE and 0.2% patients treated with vehicle nasal spray. There were no patients with nasal septal perforation in either treatment group. Somnolence was reported in 1 patient treated with PATANASE and 1 patient treated with vehicle nasal spray. Weight increase was reported in 6 patients treated with PATANASE and 1 patient treated with vehicle nasal spray. Depression or worsening of depression occurred in 9 patients treated with PATANASE and in 5 patients treated with vehicle nasal spray. Three patients, 2 of whom had preexisting histories of depression, who received PATANASE were hospitalized for depression compared to none who received vehicle nasal spray.

In a second 12-month, placebo-controlled, safety trial (vehicle nasal spray), 459 patients 12 years of age and older with perennial allergic rhinitis were treated with two sprays per nostril of an investigational formulation of PATANASE containing povidone (not the commercially marketed formulation) and 465 patients were treated with 2 sprays of a vehicle nasal spray containing povidone. Nasal septal perforations were reported in one patient treated with the investigational formulation of PATANASE and 2 patients treated with the vehicle nasal spray. Epistaxis was reported in 19% of patients treated with the investigational formulation of PATANASE and 12% of patients treated with vehicle nasal spray. Somnolence was reported in 3 patients treated with the investigational formulation of PATANASE compared to 1 patient treated with vehicle nasal spray. Fatigue was reported in 5 patients treated with the investigational formulation of PATANASE compared to 1 patient treated with vehicle nasal spray.

In a third 3-arm, 12-month placebo-controlled, safety trial (vehicle nasal spray), conducted post approval, 1026 patients 12 years of age and older with perennial allergic rhinitis were randomized to treatment with PATANASE (343 patients), a 3.7 pH vehicle nasal spray (341 patients), or a 7.0 pH vehicle nasal spray (342 patients). All treatments were administered as two sprays per nostril, twice daily. Overall, 5% of PATANASE patients, 2% of 3.7 pH vehicle patients and 3% of 7.0 pH vehicle patients discontinued due to adverse reactions. The most frequently reported adverse reaction was epistaxis, which occurred in 24% of patients treated with PATANASE, 20% of patients treated with 3.7 pH vehicle nasal spray, and 23% of patients treated with 7.0 Ph vehicle nasal spray. Epistaxis resulted in the discontinuation of 2 patients treated with PATANASE and 1 patient treated with 7.0 pH vehicle nasal spray. Nasal septal perforation was reported for one patient treated with the 3.7 pH vehicle nasal spray. Nasal ulcerations occurred in 9% of patients treated with PATANASE, 8% of patients treated with 3.7 pH vehicle nasal spray, and 9% of patients treated with 7.0 pH vehicle nasal spray. Nasal ulceration resulted in the discontinuation of 1 patient treated with PATANASE. Hyposmia and anosmia were each reported by one patient treated with PATANASE. Neither somnolence nor weight loss was reported. Depression occurred in 3 patients treated with PATANASE, 2 patients treated with 3.7 pH vehicle nasal spray, and 3 patients treated with 7.0 pH vehicle nasal spray.

There were no long-term clinical trials in children below 12 years of age.

Postmarketing Experience

During the post approval use of PATANASE, the following adverse reactions have been identified. 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. The most common adverse reactions reported include dizziness, dysgeusia, epistaxis, headache, nasal discomfort, oropharyngeal pain, and somnolence. Additionally, hyposmia and anosmia have been reported with the use of PATANASE.