FDA label d422f075-b2ad-493c-a2a2-9c99fb356f27

5 WARNINGS AND PRECAUTIONS • Epistaxis, nasal ulceration, and nasal septal perforation. Monitor patients periodically for signs of adverse effects on the nasal mucosa. Discontinue if ulcerations or perforations occur. Avoid use in patients with nasal disease other than allergic rhinitis (5.1). • Avoid engaging in hazardous occupations requiring complete mental alertness and coordination such as driving or operating machinery when taking olopatadine hydrochloride nasal spray (5.2). • Avoid concurrent use of alcohol or other central nervous system depressants with olopatadine hydrochloride nasal spray (5.2). 5.1 Local Nasal Effects Epistaxis and Nasal Ulceration : In placebo (vehicle nasal spray)-controlled clinical trials of 2 weeks to 12 months duration, epistaxis and nasal ulcerations were reported [ see Adverse Reactions (6) ]. Nasal Septal Perforation : Three placebo (vehicle nasal spray)-controlled long term (12 months) safety trials were conducted. In the first safety trial, patients were treated with an investigational formulation of olopatadine hydrochloride nasal spray containing povidone (not the commercially marketed formulation) or a vehicle nasal spray containing povidone. Nasal septal perforations were reported in one patient treated with the investigational formulation of olopatadine hydrochloride nasal spray and 2 patients treated with the vehicle nasal spray. In the second safety trial with olopatadine hydrochloride nasal spray, which does not contain povidone, there were no reports of nasal septal perforation. In the third safety trial, one patient exposed to the 3.7 pH vehicle nasal spray (containing no povidone) reported a nasal septal perforation [ see Adverse Reactions (6) ]. Before starting olopatadine hydrochloride nasal spray, conduct a nasal examination to ensure that patients are free of nasal disease other than allergic rhinitis. Perform nasal examinations periodically for signs of adverse effects on the nasal mucosa and consider stopping olopatadine hydrochloride nasal spray if patients develop nasal ulcerations. 5.2 Activities Requiring Mental Alertness In clinical trials, the occurrence of somnolence has been reported in some patients taking olopatadine hydrochloride nasal spray [ see Adverse Reactions (6) ]. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as driving or operating machinery after administration of olopatadine hydrochloride nasal spray. Concurrent use of olopatadine hydrochloride nasal spray with alcohol or other central nervous system depressants should be avoided because additional reductions in alertness and additional impairment of central nervous system performance may occur.

6 ADVERSE REACTIONS The most clinically significant adverse reactions described in other sections of labeling include; • Epistaxis, Nasal Ulceration, and Nasal Septal Perforation [ see Warnings and Precautions (5.1) ] • Somnolence [ see Warnings and Precautions (5.2) ] The most common (>1%) adverse reactions included bitter taste, headache, epistaxis, pharyngolaryngeal pain, post-nasal drip, cough, and urinary tract infection in patients 12 years of age and older and epistaxis, headache, upper respiratory tract infection, bitter taste, pyrexia, and rash in patients 6 to 11 years of age (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The safety data described below reflect exposure to olopatadine hydrochloride nasal spray in 2,770 patients with seasonal or perennial allergic rhinitis in 10 controlled clinical trials of 2 weeks to 12 months duration. The safety data from adults and adolescents are based upon 6 placebo (3.7 pH vehicle nasal spray or 7.0 pH vehicle nasal spray)-controlled clinical trials in which 1,834 patients with seasonal or perennial allergic rhinitis (652 males and 1,182 females) 12 years of age and older were treated with olopatadine hydrochloride nasal spray two sprays per nostril twice daily. There were 1,180 patients (olopatadine hydrochloride nasal spray, 587; vehicle nasal spray, 593) that participated in 3 efficacy and safety trials of 2 weeks duration. There were 2,840 patients (olopatadine hydrochloride nasal spray, 1,247; 3.7 pH vehicle nasal spray, 1,251; 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 olopatadine hydrochloride nasal spray was 77% white, 9% black, and 14% other. The incidence of discontinuation due to adverse reactions in these controlled clinical trials was comparable for olopatadine hydrochloride nasal spray and vehicle nasal spray. Overall, 4.7% of the 1,834 adult and adolescent patients across all 6 studies treated with olopatadine hydrochloride nasal spray, 3.5% of the 1,844 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 6-11 years of age are based upon 3 clinical trials in which 870 children with seasonal allergic rhinitis (376 females and 494 males) were treated with olopatadine hydrochloride nasal spray 1 or 2 sprays per nostril twice daily for 2 weeks. The racial distribution of pediatric patients receiving olopatadine hydrochloride nasal spray 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 olopatadine hydrochloride nasal spray and vehicle nasal spray. Overall, 1.4% of the 870 pediatric patients across all 3 studies treated with olopatadine hydrochloride nasal spray and 1.3% of the 872 pediatric patients treated with vehicle nasal spray discontinued due to adverse reactions. Safety information for pediatric patients 2 to 5 years of age is obtained from one vehicle-controlled study of 2 weeks duration [ see Pediatric Use (8.4) ]. 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 in Short-Term (2-week) Trials: There were 1,180 patients 12 years of age and older (olopatadine hydrochloride nasal spray), 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 olopatadine hydrochloride nasal spray) that occurred more frequently in patients treated with olopatadine hydrochloride nasal spray compared with vehicle nasal spray in the 3 clinical trials of 2 weeks duration. 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 1,742 pediatric patients 6 to 11 years of age (Olopatadine nasal spray, 870; vehicle nasal spray, 872) with seasonal allergic rhinitis 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 olopatadine hydrochloride nasal spray. One study evaluated the safety of olopatadine hydrochloride nasal spray at doses of 1 and 2 sprays per nostril twice daily in 1188 patients, in which 298 were exposed to olopatadine hydrochloride nasal spray 1 spray, 296 were exposed to olopatadine hydrochloride nasal spray 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 6-11 years of age treated with olopatadine hydrochloride nasal spray 1 spray/nostril) that occurred more frequently with olopatadine hydrochloride nasal spray compared with vehicle nasal spray. There were no differences in the incidence of adverse reactions based on gender, race, or ethnicity. Pediatric Patients 2 to 5 Years of Age: The safety of olopatadine hydrochloride nasal spray at a dose of 1 spray per nostril twice daily was evaluated in one 2-week vehicle-controlled study in 132 patients (olopatadine hydrochloride nasal spray, 66; vehicle nasal spray, 66) 2 to 5 years of age with allergic rhinitis [ see Pediatric Use (8.4) ]. Long-Term (12-month) Safety Trials: In a 12-month, placebo (vehicle nasal spray)-controlled, safety trial, 890 patients 12 years of age and older with perennial allergic rhinitis were randomized to treatment with olopatadine hydrochloride nasal spray 2 sprays per nostril twice daily (445 patients) or vehicle nasal spray (445 patients). In the olopatadine hydrochloride nasal spray 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 event. The most frequently reported adverse reaction was epistaxis, which occurred in 25% of patients treated with olopatadine hydrochloride nasal spray and 28% in patients treated with vehicle nasal spray. Epistaxis resulted in discontinuation of 0.9% of patients treated with olopatadine hydrochloride nasal spray and 0.2% of patients treated with vehicle nasal spray. Nasal ulcerations occurred in 10% of patients treated with olopatadine hydrochloride nasal spray and 9% of patients treated with vehicle nasal spray. Nasal ulcerations resulted in discontinuation of 0.4% of patients treated with olopatadine hydrochloride nasal spray 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 olopatadine hydrochloride nasal spray and 1 patient treated with vehicle nasal spray. Weight increase was reported in 6 patients treated with olopatadine hydrochloride nasal spray and 1 patient treated with vehicle nasal spray. Depression or worsening of depression occurred in 9 patients treated with olopatadine hydrochloride nasal spray and in 5 patients treated with vehicle nasal spray. Three patients, two of whom had pre-existing histories of depression, who received olopatadine hydrochloride nasal spray were hospitalized for depression compared to none who received vehicle nasal spray. In a second 12-month, placebo (vehicle nasal spray)-controlled, safety trial, 459 patients 12 years of age and older with perennial allergic rhinitis were treated with 2 sprays per nostril of an investigational formulation of olopatadine hydrochloride nasal spray 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 olopatadine hydrochloride nasal spray and 2 patients treated with the vehicle nasal spray. Epistaxis was reported in 19% of patients treated with the investigational formulation of olopatadine hydrochloride nasal spray and 12% of patients treated with vehicle nasal spray. Somnolence was reported in 3 patients treated with the investigational formulation of olopatadine hydrochloride nasal spray compared to 1 patient treated with vehicle nasal spray. Fatigue was reported in 5 patients treated with the investigational formulation of olopatadine hydrochloride nasal spray compared to 1 patient treated with vehicle nasal spray. In a third 3-arm 12-month, placebo (vehicle nasal spray)-controlled, safety trial conducted post approval, 1,026 patients 12 years of age and older with perennial allergic rhinitis were randomized to treatment with olopatadine hydrochloride nasal spray (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 2 sprays per nostril, twice daily. Overall, 5% of olopatadine hydrochloride nasal spray patients, 2% of 3.7 pH vehicle patients and 3% of 7.0 pH vehicle patients discontinued due to adverse events. The most frequently reported adverse event was epistaxis, which occurred in 24% of patients treated with olopatadine hydrochloride nasal spray, 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 olopatadine hydrochloride nasal spray 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 olopatadine hydrochloride nasal spray, 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 olopatadine hydrochloride nasal spray. Hyposmia and anosmia were each reported by one patient treated with olopatadine hydrochloride nasal spray. Neither somnolence nor weight loss was reported. Depression occurred in 3 patients treated with olopatadine hydrochloride nasal spray, 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. Table 1 Table 2.jpg 6.2 Post-Marketing Experience During the post approval use of olopatadine hydrochloride nasal spray, 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 olopatadine hydrochloride nasal spray.