e additional reductions in alertness and additional impairment of central nervous system performance may occur [see drug interactions (7.1) ] .

otor rhinitis is two sprays per nostril twice daily. 2.3 important administration instructions administer azelastine hcl nasal spray, 0.1% by the intranasal route only. priming: prime azelastine hcl nasal spray, 0.1% before initial use by releasing 4 sprays or until a fine mist appears. when azelastine hcl nasal spray, 0.1% has not been used for 3 or more days, reprime with 2 sprays or until a fine mist appears. avoid spraying azelastine hcl nasal spray, 0.1% into the eyes.

placebo- and active-controlled, 2-day to 8-week clinical trials which included 391 patients, 12 years of age and older, with seasonal allergic rhinitis who received azelastine hcl nasal spray, 0.1% at a dose of 2 sprays per nostril twice daily. in placebo-controlled efficacy trials, the incidence of discontinuation due to adverse reactions in patients receiving azelastine hcl nasal spray, 0.1% and vehicle placebo was 2.2% and 2.8%, respectively. table 1 contains adverse reactions that were reported with frequencies ≥2% in the azelastine hcl nasal spray, 0.1% 2 sprays per nostril twice daily treatment group and more frequently than placebo. table 1: adverse reactions reported in ≥2% incidence in placebo-controlled trials in patients with seasonal allergic rhinitis [n (%)] azelastine hcl nasal spray, 0.1% n = 391 vehicle placebo n = 353 bitter taste 77 (19.7%) 2 (0.6%) headache 58 (14.8%) 45 (12.7%) somnolence 45 (11.5%) 19 (5.4%) nasal burning 16 (4.1%) 6 (1.7%) pharyngitis 15 (3.8%) 10 (2.8%) paroxysmal sneezing 12 (3.1%) 4 (1.1%) dry mouth 11 (2.8%) 6 (1.7%) nausea 11 (2.8%) 4 (1.1%) rhinitis 9 (2.3%) 5 (1.4%) fatigue 9 (2.3%) 5 (1.4%) dizziness 8 (2.0%) 5 (1.4%) epistaxis 8 (2.0%) 5 (1.4%) weight increase 8 (2.0%) 0 (0.0%) azelastine hcl nasal spray, 0.1% one spray per nostril twice daily adverse experience information for azelastine hcl nasal spray, 0.1% at a dose of one spray per nostril twice daily is derived from two placebo-controlled 2-week clinical studies which included 276 patients 12 years of age and older with seasonal allergic rhinitis. the incidence of discontinuation due to adverse reactions in patients receiving azelastine hcl nasal spray, 0.1% and vehicle placebo was 0.0% and 0.8%, respectively. bitter taste was reported in 8.3% of patients compared to none in the placebo group. somnolence was reported in 0.4% of patients compared to none in the placebo group. a total of 176 patients 5 to 11 years of age were exposed to azelastine hcl nasal spray, 0.1% at a dose of 1 spray each nostril twice daily in 3 placebo-controlled studies. in these studies, adverse reactions that occurred more frequently in patients treated with azelastine hcl nasal spray, 0.1% than with placebo, and that were not represented in the adult adverse reactions table above include rhinitis/cold symptoms (17.0% vs. 9.5%), cough (11.4% vs. 8.3%), conjunctivitis (5.1% vs. 1.8%), and asthma (4.5% vs. 4.1%). adverse reactions <2% in azelastine hcl nasal spray, 0.1% one or two sprays per nostril twice daily the following reactions were observed infrequently (<2% and exceeding placebo incidence) in patients who received azelastine hcl nasal spray, 0.1% dosed at 1 or 2 sprays per nostril twice daily in u.s. clinical trials. cardiovascular: flushing, hypertension, tachycardia. dermatological: contact dermatitis, eczema, hair and follicle infection, furunculosis, skin laceration. digestive: constipation, gastroenteritis, glossitis, ulcerative stomatitis, vomiting, increased sgpt, aphthous stomatitis, diarrhea, toothache. metabolic and nutritional: increased appetite. musculoskeletal: myalgia, temporomandibular dislocation, rheumatoid arthritis. neurological: hyperkinesia, hypoesthesia, vertigo. psychological: anxiety, depersonalization, depression, nervousness, sleep disorder, thinking abnormal. respiratory: bronchospasm, coughing, throat burning, laryngitis, bronchitis, dry throat, nocturnal dyspnea, nasopharyngitis, nasal congestion, pharyngolaryngeal pain, sinusitis, nasal dryness, paranasal sinus hypersecretion, post nasal drip. special senses: conjunctivitis, eye abnormality, eye pain, watery eyes, taste loss. urogenital: albuminuria, amenorrhea, breast pain, hematuria, increased urinary frequency. whole body: allergic reaction, back pain, herpes simplex, viral infection, malaise, pain in extremities, abdominal pain, pyrexia. vasomotor rhinitis adverse experience information for azelastine hcl nasal spray, 0.1% is derived from two placebo-controlled clinical studies which included 216 patients 12 years and older with vasomotor rhinitis who received azelastine hcl nasal spray, 0.1% at a dose of 2 sprays per nostril twice daily for up to 28 days. the incidence of discontinuation due to adverse reactions in patients receiving azelastine hcl nasal spray, 0.1% and vehicle placebo was 2.8% and 2.9%, respectively. the following adverse reactions were reported with frequencies ≥ 2% in the azelastine hcl nasal spray, 0.1% treatment group and more frequently than placebo. table 2: adverse reactions reported in ≥2% incidence in placebo-controlled trials in patients with vasomotor rhinitis [n (%)] azelastine hcl nasal spray, 0.1% n = 216 vehicle placebo n = 210 bitter taste 42 (19.4%) 5 (2.4%) headache 17 (7.9%) 16 (7.6%) dysesthesia 17 (7.9%) 7 (3.3%) rhinitis 12 (5.6%) 5 (2.4%) epistaxis 7 (3.2%) 5 (2.4%) sinusitis 7 (3.2%) 4 (1.9%) somnolence 7 (3.2%) 2 (1.0%) reactions observed infrequently (<2% and exceeding placebo incidence) in patients who received azelastine hcl nasal spray, 0.1% (2 sprays/nostril twice daily) in u.s. clinical trials in vasomotor rhinitis were similar to those observed in u.s. clinical trials in seasonal allergic rhinitis. in controlled trials involving nasal and oral azelastine hcl formulations, there were infrequent occurrences of hepatic transaminase elevations. 6.2 postmarketing experience during the post approval use of azelastine hcl nasal spray, 0.1%, 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. adverse reactions reported include: anaphylaxis, application site irritation, atrial fibrillation, chest pain, confusion, dyspnea, facial edema, involuntary muscle contractions, nasal sores, palpitations, paresthesia, parosmia, pruritus, rash, disturbance or loss of sense of smell and/or taste, tolerance, urinary retention, vision abnormal and xerophthalmia.

ons is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background 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 embryo-fetal development study in mice dosed during the period of organogenesis, azelastine hcl caused embryo-fetal death, structural abnormalities (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification, and decreased fetal weight at approximately 300 times the maximum recommended human daily intranasal dose (mrhdid) in adults (on a mg/m 2 basis at a maternal oral dose of 68.6 mg/kg/day), which also caused maternal toxicity as evidenced by decreased maternal body weight. neither fetal nor maternal effects occurred in mice at approximately 15 times the mrhdid in adults (on a mg/m 2 basis at a maternal oral dose of 3 mg/kg/day). in an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 7 to 17, azelastine hcl caused structural abnormalities (oligo-and brachydactylia), delayed ossification, and skeletal variations, in the absence of maternal toxicity, at approximately 270 times the mrhdid in adults (on a mg/m 2 basis at a maternal oral dose of 30 mg/kg/day). azelastine hcl caused embryo-fetal death and decreased fetal weight and severe maternal toxicity at approximately 610 times the mrhdid (on a mg/m 2 basis at a maternal oral dose of 68.6 mg/kg/day). neither fetal nor maternal effects occurred at approximately 20 times the mrhdid (on a mg/m 2 basis at a maternal oral dose of 2 mg/kg/day). in an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, azelastine hcl caused abortion, delayed ossification and decreased fetal weight and severe maternal toxicity at approximately 530 times the mrhdid in adults (on a mg/m 2 basis at a maternal oral dose of 30 mg/kg/day). neither fetal nor maternal effects occurred at approximately 5 times the mrhdid (on a mg/m 2 basis at a maternal oral dose of 0.3 mg/kg/day). in a prenatal and postnatal development study in pregnant rats dosed from late in the gestation period and through the lactation period from gestation day 17 through lactation day 21, azelastine hcl produced no adverse developmental effects on pups at maternal doses up to approximately 270 times the mrhdid (on mg/m 2 basis at a maternal dose of 30 mg/kg/day).

effects of concomitantly administered oral azelastine hcl and erythromycin or ketoconazole were conducted. these drugs had no effect on qtc based on analysis of serial electrocardiograms. at a dose approximately 8 times the maximum recommended dose, azelastine hcl does not prolong the qtc interval to any clinically relevant extent. 12.3 pharmacokinetics absorption: after intranasal administration, the systemic bioavailability of azelastine hcl is approximately 40%. maximum plasma concentrations (c max ) are achieved in 2 to 3 hours. azelastine hcl administered intranasally at doses above two sprays per nostril twice daily for 29 days resulted in greater than proportional increases in c max and area under the curve (auc) for azelastine. distribution: based on intravenous and oral administration, the steady-state volume of distribution is 14.5 l/kg. in vitro studies with human plasma indicate that the plasma protein binding of azelastine and its metabolite, desmethylazelastine, are approximately 88% and 97%, respectively. metabolism: azelastine is oxidatively metabolized to the principal active metabolite, desmethylazelastine, by the cytochrome p450 enzyme system. the specific p450 isoforms responsible for the biotransformation of azelastine have not been identified. after intranasal dosing of azelastine hcl to steady-state, plasma concentrations of desmethylazelastine range from 20% to 50% of azelastine concentrations. limited data indicate that the metabolite profile is similar when azelastine hcl is administered via the intranasal or oral route. elimination: based on intravenous and oral administration, the elimination half-life and plasma clearance are 22 hours and 0.5 l/h/kg, respectively. approximately 75% of an oral dose of radiolabeled azelastine hcl was excreted in the feces with less than 10% as unchanged azelastine. special populations: hepatic impairment: following oral administration, pharmacokinetic parameters were not influenced by hepatic impairment. renal impairment: based on oral, single-dose studies, renal insufficiency (creatinine clearance <50 ml/min) resulted in a 70% to 75% higher c max and auc compared to normal subjects. time to maximum concentration was unchanged. age: following oral administration, pharmacokinetic parameters were not influenced by age. gender: following oral administration, pharmacokinetic parameters were not influenced by gender. race: the effect of race has not been evaluated. drug-drug interactions: erythromycin: no significant pharmacokinetic interaction was observed with the co-administration of orally administered azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days). in this study, co-administration of orally administered azelastine with erythromycin resulted in c max of 5.36 ± 2.6 ng/ml and auc of 49.7 ± 24 ng•h/ml for azelastine, whereas, administration of azelastine alone resulted in c max of 5.57 ± 2.7 ng/ml and auc of 48.4 ± 24 ng•h/ml for azelastine. cimetidine and ranitidine: in a multiple-dose, steady-state drug interaction trial in healthy subjects, cimetidine (400 mg twice daily) increased orally administered mean azelastine (4 mg twice daily) concentrations by approximately 65%. no pharmacokinetic interaction was observed with co-administration of orally administered azelastine (4 mg twice daily) with ranitidine hydrochloride (150 mg twice daily). oral co-administration of azelastine with ranitidine resulted in c max of 8.89 ±3.28 ng/ml and auc of 88.22 ± 40.43 ng•h/ml for azelastine, whereas, azelastine when administered alone resulted in c max of 7.83 ± 4.06 ng/ml and auc of 80.09 ± 43.55 ng•h/ml for azelastine. theophylline: no significant pharmacokinetic interaction was observed with the co-administration of an oral 4 mg dose of azelastine hcl twice daily and theophylline 300 mg or 400 mg twice daily.

ady-state, plasma concentrations of desmethylazelastine range from 20% to 50% of azelastine concentrations. limited data indicate that the metabolite profile is similar when azelastine hcl is administered via the intranasal or oral route. elimination: based on intravenous and oral administration, the elimination half-life and plasma clearance are 22 hours and 0.5 l/h/kg, respectively. approximately 75% of an oral dose of radiolabeled azelastine hcl was excreted in the feces with less than 10% as unchanged azelastine. special populations: hepatic impairment: following oral administration, pharmacokinetic parameters were not influenced by hepatic impairment. renal impairment: based on oral, single-dose studies, renal insufficiency (creatinine clearance <50 ml/min) resulted in a 70% to 75% higher c max and auc compared to normal subjects. time to maximum concentration was unchanged. age: following oral administration, pharmacokinetic parameters were not influenced by age. gender: following oral administration, pharmacokinetic parameters were not influenced by gender. race: the effect of race has not been evaluated. drug-drug interactions: erythromycin: no significant pharmacokinetic interaction was observed with the co-administration of orally administered azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days). in this study, co-administration of orally administered azelastine with erythromycin resulted in c max of 5.36 ± 2.6 ng/ml and auc of 49.7 ± 24 ng•h/ml for azelastine, whereas, administration of azelastine alone resulted in c max of 5.57 ± 2.7 ng/ml and auc of 48.4 ± 24 ng•h/ml for azelastine. cimetidine and ranitidine: in a multiple-dose, steady-state drug interaction trial in healthy subjects, cimetidine (400 mg twice daily) increased orally administered mean azelastine (4 mg twice daily) concentrations by approximately 65%. no pharmacokinetic interaction was observed with co-administration of orally administered azelastine (4 mg twice daily) with ranitidine hydrochloride (150 mg twice daily). oral co-administration of azelastine with ranitidine resulted in c max of 8.89 ±3.28 ng/ml and auc of 88.22 ± 40.43 ng•h/ml for azelastine, whereas, azelastine when administered alone resulted in c max of 7.83 ± 4.06 ng/ml and auc of 80.09 ± 43.55 ng•h/ml for azelastine. theophylline: no significant pharmacokinetic interaction was observed with the co-administration of an oral 4 mg dose of azelastine hcl twice daily and theophylline 300 mg or 400 mg twice daily.

610 times the mrhdid on a mg/m 2 basis), the duration of estrous cycles was prolonged and copulatory activity and the number of pregnancies were decreased. the numbers of corpora lutea and implantations were decreased; however, pre-implantation loss was not increased.

mg/m 2 basis), the duration of estrous cycles was prolonged and copulatory activity and the number of pregnancies were decreased. the numbers of corpora lutea and implantations were decreased; however, pre-implantation loss was not increased.

treated with azelastine hcl nasal spray, 0.1% two sprays per nostril twice daily versus placebo treatment n baseline ls mean (sd) change from baseline (sd) treatment difference p-value trial 1: 12 hour am and pm reflective msc azelastine hcl nasal spray, 0.1% 63 11.48 (4.13) -3.05 (3.51) 1.98 <0.01 placebo nasal spray 60 10.84 (4.53) -1.07 (3.52) trial 2: 12 hour am and pm reflective msc azelastine hcl nasal spray, 0.1% 63 12.50 (4.5) -4.10 (3.46) 2.03 <0.01 placebo nasal spray 63 12.18 (4.64) -2.07 (4.01) trial 3: 12 hour am and pm reflective msc azelastine hcl nasal spray, 0.1% 66 12.04 (4.03) -3.31 (3.74) 1.35 0.04 placebo nasal spray 66 11.66 (3.96) -1.96 (3.57) * major symptom complex (msc): average of individual symptoms of nose blows, sneezes, runny nose/sniffles, itchy nose, and watery eyes as assessed by patients on a 0 to 5 categorical scale. in dose-ranging trials, administration of azelastine hcl nasal spray, 0.1% two sprays per nostril twice daily resulted in a statistically significant decrease in symptoms compared to saline placebo within 3 hours after initial dosing and persisted over the 12-hour dosing interval. one spray per nostril twice daily the efficacy and safety of azelastine hcl nasal spray, 0.1% were evaluated in two placebo-controlled clinical trials of azelastine hcl nasal spray, 0.1% including 275 patients with seasonal allergic rhinitis who received one spray per nostril twice a day for up to 2 weeks. assessment of efficacy was based on the 12-hour reflective total nasal symptom score [rtnss]. rtnss is calculated as the sum of the patients scoring of four individual nasal symptoms (runny nose, sneezing, itchy nose, and nasal congestion) as assessed by patients on a 0 to 3 categorical scale. the primary efficacy endpoint was the change from baseline to day 14 in rtnss. the mean change from baseline in rtnss was greater in patients receiving azelastine hcl nasal spray, 0.1% one spray per nostril twice daily than those receiving placebo (table 4). table 4: mean change from baseline in reflective tnss* in adults and adolescents ≥12 years with seasonal allergic rhinitis treated with azelastine hcl nasal spray, 0.1% one spray per nostril twice daily versus placebo treatment n baseline ls mean (sd) change from baseline (sd) treatment difference p-value trial 4: 12 hour am and pm reflective tnss azelastine hcl nasal spray, 0.1% 138 16.34 (4.22) -2.69 (4.79) 1.38 0.01 placebo nasal spray 141 17.21 (4.32) -1.31 (4.29) trial 5: 12 hour am and pm reflective tnss azelastine hcl nasal spray, 0.1% 137 16.62 (4.20) -3.68 (4.16) 1.18 0.02 placebo nasal spray 136 16.84 (4.77) -2.50 (4.01) * total nasal symptom score (tnss): average of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestion as assessed by patients on a 0 to 3 categorical scale. two-week studies comparing the efficacy (and safety) of azelastine hcl nasal spray, 0.1% two sprays per nostril twice daily versus one spray per nostril twice daily were not conducted. 14.2 vasomotor rhinitis the efficacy and safety of azelastine hcl nasal spray, 0.1% were evaluated in two placebo-controlled clinical trials of azelastine hcl nasal spray, 0.1% including 216 patients with vasomotor rhinitis who received two sprays per nostril twice a day for up to 4 weeks. these patients had vasomotor rhinitis for at least one year, negative skin tests to indoor and outdoor aeroallergens, negative nasal smears for eosinophils, and negative sinus x-rays. azelastine hcl nasal spray, 0.1% demonstrated a significantly greater decrease in a symptom complex comprised of rhinorrhea, post nasal drip, nasal congestion, and sneezing compared to placebo.

€œexp” printed on the medicine label and carton. storage: store upright at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. protect from freezing.

de bitter taste, headache, somnolence, dysesthesia, rhinitis, nasal burning, pharyngitis, epistaxis, sinusitis, paroxysmal sneezing, nausea, dry mouth, fatigue, dizziness, and weight increase [see adverse reactions (6.1) ] . priming instruct patients to prime the pump before initial use and when azelastine hcl nasal spray, 0.1% has not been used for 3 or more days [see dosage and administration (2.3) ] . keep spray out of eyes instruct patients to avoid spraying azelastine hcl nasal spray, 0.1% into their eyes. keep out of children’s reach instruct patients to keep azelastine hcl nasal spray, 0.1% out of the reach of children. if a child accidentally ingests azelastine hcl nasal spray, 0.1%, seek medical help or call a poison control center immediately. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 10-2018-02

for a complete list of ingredients in azelastine hcl nasal spray, 0.1%. pregnant, or plan to become pregnant. breastfeeding, or plan to breastfeed. it is not known if azelastine hcl passes into your breast milk. you and your healthcare provider should decide if you will use azelastine hcl nasal spray, 0.1% if you plan to breastfeed. tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. azelastine hcl nasal spray, 0.1% and other medicines may affect each other, causing side effects. how should i use azelastine hcl nasal spray, 0.1%? read the instructions for use at the end of this leaflet for information about the right way to use azelastine hcl nasal spray, 0.1%. spray azelastine hcl nasal spray, 0.1% in your nose only. do not spray it into your eyes or mouth. use azelastine hcl nasal spray, 0.1% exactly as your healthcare provider tells you to use it. do not use more than your healthcare provider tells you. throw away your azelastine hcl nasal spray, 0.1% bottle after using 200 sprays. even though the bottle may not be completely empty, you may not get the correct dose of medicine. if you use too much or a child accidentally swallows azelastine hcl nasal spray, 0.1%, call your healthcare provider or go to the nearest hospital emergency room right away. what should i avoid while using azelastine hcl nasal spray, 0.1%? azelastine hcl nasal spray, 0.1% can cause sleepiness: do not drive, operate machinery, or do other dangerous activities until you know how azelastine hcl nasal spray, 0.1% affects you. do not drink alcohol or take other medicines that may cause you to feel sleepy while using azelastine hcl nasal spray, 0.1%. it may make your sleepiness worse. what are the possible side effects of azelastine hcl nasal spray, 0.1%? the most common side effects of azelastine hcl nasal spray, 0.1% include: unusual bitter taste headache sleepiness nose burning, pain or discomfort runny nose scratchy or sore throat nosebleeds inflammation or swelling of the sinuses sneezing nausea dry mouth fatigue dizziness weight increase tell your healthcare provider if you have any side effect that bothers you or that does not go away. these are not all of the possible side effects of azelastine hcl nasal spray, 0.1%. for more information, ask your healthcare provider or pharmacist. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store azelastine hcl nasal spray, 0.1%? keep azelastine hcl nasal spray, 0.1% upright at 68° to 77°f (20° to 25°c). do not freeze azelastine hcl nasal spray, 0.1%. do not use azelastine hcl nasal spray, 0.1% after the expiration date “exp” on the medicine label and box. keep azelastine hcl nasal spray, 0.1% and all medicines out of reach of children. general information about the safe and effective use of azelastine hcl nasal spray, 0.1%. medicines are sometimes prescribed for conditions other than those listed in a patient information leaflet. do not use azelastine hcl nasal spray, 0.1% for a condition for which it was not prescribed. do not give azelastine hcl nasal spray, 0.1% to other people, even if they have the same symptoms that you have. it may harm them. this patient information leaflet summarizes the most important information about azelastine hcl nasal spray, 0.1%. if you would like more information, talk with your healthcare provider. you can ask your pharmacist or healthcare provider for information about azelastine hcl nasal spray, 0.1% that is written for health professionals. for more information call 1-877-835-5472. what are the ingredients in azelastine hcl nasal spray, 0.1%? active ingredient: azelastine hcl, usp inactive ingredients: benzalkonium chloride, citric acid, dibasic sodium phosphate, edetate disodium, hypromellose, purified water (ph 6.8) and sodium chloride. * trademarks are the property of their respective owners. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 10-2018-02