NDC 50090-2330 Azelastine Hydrochloride

Azelastine Hydrochloride

NDC Product Code 50090-2330

NDC 50090-2330-0

Package Description: 1 BOTTLE, SPRAY in 1 CARTON > 200 SPRAY, METERED in 1 BOTTLE, SPRAY

NDC Product Information

Azelastine Hydrochloride with NDC 50090-2330 is a a human prescription drug product labeled by A-s Medication Solutions. The generic name of Azelastine Hydrochloride is azelastine hydrochloride. The product's dosage form is spray, metered and is administered via nasal form.

Labeler Name: A-s Medication Solutions

Dosage Form: Spray, Metered - A non-pressurized dosage form consisting of valves which allow the dispensing of a specified quantity of spray upon each activation.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Azelastine Hydrochloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • AZELASTINE HYDROCHLORIDE 137 ug/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)
  • EDETATE DISODIUM (UNII: 7FLD91C86K)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)
  • SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM (UNII: GR686LBA74)
  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Nasal - Administration to the nose; administered by way of the nose.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Histamine H1 Receptor Antagonists - [MoA] (Mechanism of Action)
  • Histamine-1 Receptor Antagonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: A-s Medication Solutions
Labeler Code: 50090
FDA Application Number: ANDA077954 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-01-2010 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Azelastine Nasal Spray

Azelastine Nasal Spray is pronounced as (a zel' as teen)

Why is azelastine nasal spray medication prescribed?
Azelastine, an antihistamine, is used to treat hay fever and allergy symptoms including runny nose, sneezing, and itchy nose.This medication is sometimes prescribed for o...
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Azelastine Hydrochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Azelastine hydrochloride nasal spray is indicated for the treatment of the symptoms of seasonal allergic rhinitis in adults and pediatric patients 5 years and older, and for the treatment of the symptoms of vasomotor rhinitis in adults and adolescent patients 12 years and older.

2.1 Seasonal Allergic Rhinitis

The recommended dosage of azelastine hydrochloride nasal spray in adults and adolescent patients 12 years and older with seasonal allergic rhinitis is one or two sprays per nostril twice daily. The recommended dosage of azelastine hydrochloride nasal spray in pediatric patients 5 years to 11 years of age is one spray per nostril twice daily.

2.2 Vasomotor Rhinitis

The recommended dosage of azelastine hydrochloride nasal spray in adults and adolescent patients 12 years and older with vasomotor rhinitis is two sprays per nostril twice daily.

2.3 Important Administration Instructions

Administer azelastine hydrochloride nasal spray by the intranasal route only.Priming  Prime azelastine hydrochloride nasal spray before initial use by releasing 4 sprays or until a fine mist appears. When azelastine hydrochloride nasal spray has not been used for 3 or more days, reprime with 2 sprays or until a fine mist appears. Avoid spraying azelastine hydrochloride nasal spray into the eyes.

3 Dosage Forms And Strengths

Azelastine hydrochloride nasal spray is a nasal spray solution. Each spray of azelastine hydrochloride nasal spray delivers a volume of 0.137 mL solution containing 137 mcg of azelastine hydrochloride.

4 Contraindications

None.

5.1 Somnolence In Activities Requiring Mental Alertness

In clinical trials, the occurrence of somnolence has been reported in some patients taking azelastine hydrochloride nasal spray [see Adverse Reactions (6.1)]. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as operating machinery or driving a motor vehicle after administration of azelastine hydrochloride nasal spray. Concurrent use of azelastine 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 [see Drug Interactions (7.1)].

6 Adverse Reactions

Use of azelastine hydrochloride nasal spray has been associated with somnolence [see Warnings and Precautions (5.1)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.Seasonal Allergic RhinitisAzelastine hydrochloride nasal spray Two Sprays Per Nostril Twice DailyAdverse experience information for azelastine hydrochloride nasal spray is derived from six 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 hydrochloride nasal spray 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 hydrochloride nasal spray and vehicle placebo was 2.2% and 2.8%, respectively.Table 1 contains adverse reactions that were reported with frequencies ≥2% in the azelastine hydrochloride nasal spray 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 hydrochloride Nasal Spray N = 391Vehicle Placebo N = 353Bitter Taste77 (19.7%)2 (0.6%)Headache58 (14.8%)45 (12.7%)Somnolence45 (11.5%)19 (5.4%)Nasal Burning16 (4.1%)6 (1.7%)Pharyngitis15 (3.8%)10 (2.8%)Paroxysmal Sneezing12 (3.1%)4 (1.1%)Dry Mouth11 (2.8%)6 (1.7%)Nausea11 (2.8%)4 (1.1%)Rhinitis9 (2.3%)5 (1.4%)Fatigue9 (2.3%)5 (1.4%)Dizziness8 (2.0%)5 (1.4%)Epistaxis8 (2.0%)5 (1.4%)Weight Increase8 (2.0%)0 (0.0%)Azelastine hydrochloride nasal spray One Spray Per Nostril Twice DailyAdverse experience information for azelastine hydrochloride nasal spray 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 hydrochloride nasal spray 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 hydrochloride nasal spray 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 hydrochloride nasal spray 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 hydrochloride nasal spray One or Two Sprays Per Nostril Twice DailyThe following reactions were observed infrequently (<2% and exceeding placebo incidence) in patients who received azelastine hydrochloride nasal spray dosed at 1 or 2 sprays per nostril twice daily in U.S. clinical trials.CardiovascularFlushing, hypertension, tachycardia.Dermatological Contact dermatitis, eczema, hair and follicle infection, furunculosis, skin laceration.DigestiveConstipation, gastroenteritis, glossitis, ulcerative stomatitis, vomiting, increased SGPT, aphthous stomatitis, diarrhea, toothache.Metabolic and Nutritional Increased appetite.Musculoskeletal Myalgia, temporomandibular dislocation, rheumatoid arthritis.Neurological Hyperkinesias, 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 RhinitisAdverse experience information for azelastine hydrochloride nasal spray is derived from two placebo-controlled clinical studies which included 216 patients 12 years and older with vasomotor rhinitis who received azelastine hydrochloride nasal spray 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 hydrochloride nasal spray and vehicle placebo was 2.8% and 2.9%, respectively.The following adverse reactions were reported with frequencies ≥ 2% in the azelastine hydrochloride nasal spray 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 hydrochloride Nasal Spray N = 216Vehicle Placebo N = 210Bitter Taste42 (19.4%)5 (2.4%)Headache17 (7.9%)16 (7.6%)Dysesthesia17 (7.9%)7 (3.3%)Rhinitis12 (5.6%)5 (2.4%)Epistaxis7 (3.2%)5 (2.4%)Sinusitis7 (3.2%)4 (1.9%)Somnolence7 (3.2%)2 (1.0%)Reactions observed infrequently (<2% and exceeding placebo incidence) in patients who received azelastine hydrochloride nasal spray (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 hydrochloride formulations, there were infrequent occurrences of hepatic transaminase elevations.

6.2 Postmarketing Experience

During the post approval use of azelastine 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. 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.

7.1 Central Nervous System Depressants

Concurrent use of azelastine hydrochloride nasal spray with alcohol or other central nervous system depressants should be avoided because reductions in alertness and impairment of central nervous system performance may occur [see Warnings and Precautions (5.1)].

8.1 Pregnancy

Pregnancy Category C There are no adequate and well-controlled clinical studies in pregnant women. Azelastine hydrochloride has been shown to cause developmental toxicity in mice, rats, and rabbits. Azelastine hydrochloride nasal spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Teratogenic Effects In mice, azelastine hydrochloride caused embryo-fetal death, malformations (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification, and decreased fetal weight at approximately 170 times the maximum recommended human daily intranasal dose (MRHDID) in adults (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day which also caused maternal toxicity as evidenced by decreased body weight). Neither fetal nor maternal effects occurred in mice at approximately 7 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 3 mg/kg/day).In rats, azelastine hydrochloride caused malformations (oligo- and brachydactylia), delayed ossification and skeletal variations, in the absence of maternal toxicity, at approximately 150 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Azelastine hydrochloride caused embryo-fetal death and decreased fetal weight and severe maternal toxicity at approximately 340 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 15 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 2 mg/kg/day).In rabbits, azelastine hydrochloride caused abortion, delayed ossification and decreased fetal weight and severe maternal toxicity at approximately 300 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 3 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 0.3 mg/kg/day).

8.3 Nursing Mothers

It is not known whether azelastine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azelastine hydrochloride nasal spray is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of azelastine hydrochloride nasal spray for the treatment of symptoms of seasonal allergic rhinitis have been established for patients 5 years and older [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. The safety and effectiveness of azelastine hydrochloride nasal spray for the treatment of vasomotor rhinitis have been established for patients 12 years and older [see Adverse Reactions (6.1) and Clinical Studies (14.2)]. The safety and effectiveness of azelastine hydrochloride nasal spray in pediatric patients below the age of 5 years with seasonal allergic rhinitis and in pediatric patients below the age of 12 years with vasomotor rhinitis have not been established.

8.5 Geriatric Use

Clinical trials of azelastine hydrochloride nasal spray did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 Overdosage

There have been no reported overdosages with azelastine hydrochloride nasal spray. Acute overdosage by adults with this dosage form is unlikely to result in clinically significant adverse reactions, other than increased somnolence, since one bottle of azelastine hydrochloride nasal spray contains 30 mg of azelastine hydrochloride. Clinical trials in adults with single doses of the oral formulation of azelastine hydrochloride (up to 16 mg) have not resulted in increased incidence of serious adverse reactions. General supportive measures should be employed if overdosage occurs. There is no known antidote to azelastine hydrochloride nasal spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in young children. Accordingly, azelastine hydrochloride nasal spray should be kept out of the reach of children.

11 Description

Azelastine hydrochloride nasal solution 0.1% (nasal spray), 137 micrograms (mcg) per spray, is an antihistamine formulated as a metered-spray solution for intranasal administration. Azelastine hydrochloride occurs as a white, almost odorless, crystalline powder with a bitter taste. It has a molecular weight of 418.37. It is sparingly soluble in water, methanol, and propylene glycol and slightly soluble in ethanol, octanol, and glycerine. It has a melting point of about 225ºC and the pH of a saturated solution is between 5.0 and 5.4. Its chemical name is (±)-1-(2H)-phthalazinone,4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride. Its molecular formula is C22H24ClN3O•HCl with the following chemical structure:Azelastine hydrochloride nasal solution contains 0.1% azelastine hydrochloride in an aqueous solution at pH 6.8 ± 0.3. It also contains benzalkonium chloride (125 mcg/mL), citric acid, dibasic sodium phosphate, edetate disodium, hypromellose, purified water and sodium chloride. After priming [see Dosage and Administration (2.3)], each metered spray delivers a 0.137 mL mean volume containing 137 mcg of azelastine hydrochloride (equivalent to 125 mcg of azelastine base). The bottle can deliver 200 metered sprays.

12.1 Mechanism Of Action

Azelastine hydrochloride, a phthalazinone derivative, exhibits histamine H1-receptor antagonist activity in isolated tissues, animal models, and humans. Azelastine hydrochloride nasal spray is administered as a racemic mixture with no difference in pharmacologic activity noted between the enantiomers in in vitro studies. The major metabolite, desmethylazelastine, also possesses H1-receptor antagonist activity.

12.2 Pharmacodynamics

Cardiac ElectrophysiologyIn a placebo-controlled study (95 subjects with allergic rhinitis), there was no evidence of an effect of azelastine hydrochloride nasal spray (2 sprays per nostril twice daily for 56 days) on cardiac repolarization as represented by the corrected QT interval (QTc) of the electrocardiogram. Following multiple dose oral administration of azelastine 4 mg or 8 mg twice daily, the mean change in QTc was 7.2 msec and 3.6 msec, respectively.Interaction studies investigating the cardiac repolarization effects of concomitantly administered oral azelastine hydrochloride 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 hydrochloride does not prolong the QTc interval to any clinically relevant extent.

12.3 Pharmacokinetics

Absorption After intranasal administration, the systemic bioavailability of azelastine hydrochloride is approximately 40%. Maximum plasma concentrations (Cmax) are achieved in 2­ - 3 hours.Azelastine hydrochloride administered intranasally at doses above two sprays per nostril twice daily for 29 days resulted in greater than proportional increases in Cmax and area under the curve (AUC) for azelastine.DistributionBased 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.MetabolismAzelastine 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 hydrochloride 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 hydrochloride 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 hydrochloride was excreted in the feces with less than 10% as unchanged azelastine.Special PopulationsHepatic ImpairmentFollowing 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 Cmax and AUC compared to normal subjects. Time to maximum concentration was unchanged.AgeFollowing oral administration, pharmacokinetic parameters were not influenced by age.GenderFollowing oral administration, pharmacokinetic parameters were not influenced by gender.RaceThe effect of race has not been evaluated. Drug-Drug InteractionsErythromycinNo 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 Cmax 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 Cmax of 5.57 ± 2.7 ng/mL and AUC of 48.4 ± 24 ng•h/mL for azelastine.Cimetidine and RanitidineIn 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 Cmax 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 Cmax 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 hydrochloride twice daily and theophylline 300 mg or 400 mg twice daily.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

In 2-year carcinogenicity studies in rats and mice, azelastine hydrochloride did not show evidence of carcinogenicity at oral doses up to 30 mg/kg and 25 mg/kg, respectively. These doses were approximately 150 and 60 times the maximum recommended human daily intranasal dose [MRHDID] on a mg/m2 basis.Azelastine hydrochloride showed no genotoxic effects in the Ames test, DNA repair test, mouse lymphoma forward mutation assay, mouse micronucleus test, or chromosomal aberration test in rat bone marrow.Reproduction and fertility studies in rats showed no effects on male or female fertility at oral doses up to 30 mg/kg (approximately 150 times the MRHDID in adults on a mg/m2 basis). At 68.6 mg/kg (approximately 340 times the MRHDID on a mg/m2 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.

14.1 Seasonal Allergic Rhinitis

Two Sprays Per Nostril Twice DailyThe efficacy and safety of azelastine hydrochloride nasal spray were evaluated in three placebo-controlled clinical trials of azelastine hydrochloride nasal spray including 322 patients with seasonal allergic rhinitis who received two sprays per nostril twice a day for up to 4 weeks. These trials included 55 pediatric patients ages 12 to 16 years. Assessment of efficacy was based on the 12-hour reflective Total Symptom Complex (TSC) and Major Symptom Complex (MSC). The MSC was calculated as the 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. Azelastine hydrochloride nasal spray two sprays per nostril twice daily demonstrated a greater decrease in the MSC than placebo (Table 3).Table 3: Mean Change from Baseline in Reflective MSC* in Adults and Adolescents≥12 Years with Seasonal Allergic Rhinitis Treated with Azelastine hydrochloride Nasal Spray Two Sprays Per Nostril Twice Daily Versus PlaceboTreatmentNBaseline LS Mean (SD)Change from Baseline (SD)Treatment DifferenceP-valueTrial 1: 12 Hour AM and PM Reflective MSCAzelastine hydrochloride Nasal Spray6311.48 (4.13)-3.05 (3.51)1.98<0.01Placebo Nasal Spray6010.84 (4.53)-1.07 (3.52)Trial 2: 12 Hour AM and PM Reflective MSCAzelastine hydrochloride Nasal Spray6312.50 (4.5)-4.10 (3.46)2.03<0.01Placebo Nasal Spray6312.18 (4.64)-2.07 (4.01)Trial 3: 12 Hour AM and PM Reflective MSCAzelastine hydrochloride Nasal Spray6612.04 (4.03)-3.31 (3.74)1.350.04Placebo Nasal Spray6611.66 (3.96)-1.96 (3.57)*Major Symptom Comlex (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 hydrochloride nasal spray 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 DailyThe efficacy and safety of azelastine hydrochloride nasal spray were evaluated in two placebo-controlled clinical trials of azelastine hydrochloride nasal spray 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 hydrochloride nasal spray 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 hydrochloride Nasal Spray One Spray Per Nostril Twice Daily Versus PlaceboTreatmentNBaseline LS Mean (SD)Change from Baseline (SD)Treatment DifferenceP-valueTrial 4: 12 Hour AM and PM Reflective TNSSAzelastine hydrochloride Nasal Spray13816.34 (4.22)-2.69 (4.79)1.380.01Placebo Nasal Spray14117.21 (4.32)-1.31 (4.29)Trial 5: 12 Hour AM and PM Reflective TNSSAzelastine hydrochloride Nasal Spray13716.62 (4.20)-3.68 (4.16)1.180.02Placebo Nasal Spray13616.84 (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 hydrochloride nasal spray 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 hydrochloride nasal spray were evaluated in two placebo-controlled clinical trials of azelastine hydrochloride nasal spray 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 hydrochloride nasal spray demonstrated a significantly greater decrease in a symptom complex comprised of rhinorrhea, post nasal drip, nasal congestion, and sneezing compared to placebo.

16 How Supplied/Storage And Handling

Product: 50090-2330NDC: 50090-2330-0 200 SPRAY, METERED in a BOTTLE, SPRAY / 1 in a CARTON

17 Patient Counseling Information

See FDA-approved patient labeling (Patient Information and Instructions for Use).Activities Requiring Mental AlertnessSomnolence has been reported in some patients taking azelastine hydrochloride Nasal Spray. Caution patients against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as driving or operating machinery after administration of azelastine hydrochloride nasal spray [see Warnings and Precautions (5.1)].Concurrent Use of Alcohol and other Central Nervous System DepressantsInstruct patients to avoid concurrent use of azelastine hydrochloride nasal spray with alcohol or other central nervous system depressants because additional reductions in alertness and additional impairment of central nervous system performance may occur [see Warnings and Precautions (5.1)].Common Adverse ReactionsInform patients that the treatment with azelastine hydrochloride nasal spray may lead to adverse reactions, which include 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)].PrimingInstruct patients to prime the pump before initial use and when azelastine hydrochloride nasal spray has not been used for 3 or more days [see Dosage and Administration (2.3)].Keep Spray Out of EyesInstruct patients to avoid spraying azelastine hydrochloride nasal spray into their eyes.Keep Out of Children’s ReachInstruct patients to keep azelastine hydrochloride nasal spray out of the reach of children. If a child accidentally ingests azelastine hydrochloride nasal spray, seek medical help or call a poison control center immediately.APOTEX INC.AZELASTINE HYDROCHLORIDE NASAL SPRAY137 mcgManufactured byManufactured forApotex Inc.Apotex Corp.Toronto, Ontario Weston, Florida Canada M9L 1T9 33326Revised: January 2017

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