1 INDICATIONS AND USAGE Olopatadine hydrochloride nasal solution (nasal spray) is indicated for the relief of the symptoms of seasonal allergic rhinitis in adults and pediatric patients 6 years of age and older.

Olopatadine hydrochloride nasal solution (nasal spray) is an H 1 receptor antagonist indicated for the relief of the symptoms of seasonal allergic rhinitis in adults and pediatric patients 6 years of age and older.

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 and Impaired Mental Alertness [ 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 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 olopatadine hydrochloride nasal solution (nasal spray) in 2770 patients with seasonal or perennial allergic rhinitis in 10 controlled clinical trials of 2 weeks to 12 months duration.

Olopatadine hydrochloride nasal solution (nasal spray) 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 olopatadine hydrochloride nasal solution (nasal spray) two sprays per nostril twice daily.

There were 1180 patients (olopatadine hydrochloride nasal solution (nasal spray), 587; vehicle nasal spray, 593) that participated in 3 efficacy and safety trials of 2 weeks duration.

There were 2840 patients (olopatadine hydrochloride nasal solution (nasal spray), 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 olopatadine hydrochloride nasal solution (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 solution (nasal spray) and vehicle nasal spray.

Overall, 4.7% of the 1834 adult and adolescent patients across all 6 studies treated with olopatadine hydrochloride nasal solution (nasal spray), 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 seasonal allergic rhinitis (376 females and 494 males) were treated with olopatadine hydrochloride nasal solution (nasal spray) one or two sprays per nostril twice daily for 2 weeks.

The racial distribution of pediatric patients receiving olopatadine hydrochloride nasal solution (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 solution (nasal spray) and vehicle nasal spray.

Overall, 1.4% of the 870 pediatric patients across all 3 studies treated with olopatadine hydrochloride nasal solution (nasal spray) 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 (olopatadine hydrochloride nasal solution (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 solution (nasal spray)) that occurred more frequently in patients treated with olopatadine hydrochloride nasal solution (nasal spray) 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 Olopatadine Hydrochloride Nasal Solution (Nasal Spray) in Adolescent and Adult Patients 12 Years of Age and Older With Seasonal Allergic Rhinitis Adverse Reaction Adult and Adolescent Patients 12 Years and Older Olopatadine Hydrochloride Nasal Solution (Nasal Spray) N = 587 Vehicle Nasal Spray N = 593 Bitter taste 75 (12.8%) 5 (0.8%) Headache 26 (4.4%) 24 (4.0%) Epistaxis 19 (3.2%) 10 (1.7%) Pharyngolaryngeal Pain 13 (2.2%) 8 (1.3%) Post-nasal drip 9 (1.5%) 5 (0.8%) Cough 8 (1.4%) 3 (0.5%) Urinary tract infection 7 (1.2%) 3 (0.5%) CPK elevation 5 (0.9%) 2 (0.3%) Dry mouth 5 (0.9%) 1 (0.2%) Fatigue 5 (0.9%) 4 (0.7%) Influenza 5 (0.9%) 1 (0.2%) Nasopharyngitis 5 (0.9%) 4 (0.7%) Somnolence 5 (0.9%) 2 (0.3%) Throat irritation 5 (0.9%) 0 (0.0%) 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 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 solution (nasal spray).

One study evaluated the safety of olopatadine hydrochloride nasal solution (nasal spray) at doses of one and two sprays per nostril twice daily in 1188 patients, in which 298 were exposed to olopatadine hydrochloride nasal solution (nasal spray) 1 spray, 296 were exposed to olopatadine hydrochloride nasal solution (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 to 11 years of age treated with olopatadine hydrochloride nasal solution (nasal spray) one spray per nostril) that occurred more frequently with olopatadine hydrochloride nasal solution (nasal spray) 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 Olopatadine Hydrochloride Nasal Solution (Nasal Spray) in Pediatric Patients 6 to 11 Years of Age With Seasonal Allergic Rhinitis Adverse Reaction Pediatric Patients 6 to 11 Years of Age Olopatadine Hydrochloride Nasal Solution (Nasal Spray) One Spray per Nostril N = 298 Vehicle Nasal Spray One Spray per Nostril N = 297 Epistaxis Headache Upper respiratory tract infection Bitter taste 17 (5.7%) 13 (4.4%) 8 (2.6%) 3 (1.0%) 11 (3.7%) 11 (3.7%) 0 0 Pyrexia 4 (1.3%) 3 (1.0%) Rash 4 (1.3%) 0 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 olopatadine hydrochloride nasal solution (nasal spray) two sprays per nostril twice daily (445 patients) or vehicle nasal spray (445 patients).

In the olopatadine hydrochloride nasal solution (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 reaction.

The most frequently reported adverse reaction was epistaxis, which occurred in 25% of patients treated with olopatadine hydrochloride nasal solution (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 solution (nasal spray) and 0.2% of patients treated with vehicle nasal spray.

Nasal ulcerations occurred in 10% of patients treated with olopatadine hydrochloride nasal solution (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 solution (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 solution (nasal spray) and 1 patient treated with vehicle nasal spray.

Weight increase was reported in 6 patients treated with olopatadine hydrochloride nasal solution (nasal spray) and 1 patient treated with vehicle nasal spray.

Depression or worsening of depression occurred in 9 patients treated with olopatadine hydrochloride nasal solution (nasal spray) and in 5 patients treated with vehicle nasal spray.

Three patients, 2 of whom had preexisting histories of depression, who received olopatadine hydrochloride nasal solution (nasal spray) 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 olopatadine hydrochloride nasal solution (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 solution (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 solution (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 solution (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 solution (nasal spray) 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 olopatadine hydrochloride nasal solution (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 two sprays per nostril, twice daily.

Overall, 5% of olopatadine hydrochloride nasal solution (nasal spray) 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 olopatadine hydrochloride nasal solution (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 solution (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 solution (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 solution (nasal spray).

Hyposmia and anosmia were each reported by one patient treated with olopatadine hydrochloride nasal solution (nasal spray).

Neither somnolence nor weight loss was reported.

Depression occurred in 3 patients treated with olopatadine hydrochloride nasal solution (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.

6.2 Postmarketing Experience During the post approval use of olopatadine hydrochloride nasal solution (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 solution (nasal spray).