NDC 67877-477 Azelastine

Azelastine

NDC Product Code 67877-477

NDC 67877-477-50

Package Description: 1 SPRAY, METERED in 1 BOTTLE

NDC Product Information

Azelastine with NDC 67877-477 is a a human prescription drug product labeled by Ascend Laboratories, Llc. The generic name of Azelastine is azelastine. The product's dosage form is spray, metered and is administered via nasal form.

Labeler Name: Ascend Laboratories, Llc

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 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.

  • HYPROMELLOSES (UNII: 3NXW29V3WO)
  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE (UNII: 70WT22SF4B)
  • EDETATE DISODIUM (UNII: 7FLD91C86K)
  • ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)
  • BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)
  • 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.
  • 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: Ascend Laboratories, Llc
Labeler Code: 67877
FDA Application Number: ANDA208156 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: 08-18-2017 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: 12-31-2020 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 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. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

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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* Please review the disclaimer below.

Azelastine 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 HCl 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 HCl 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 HCl 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 HCl 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 HCl Nasal Spray by the intranasal route only. Priming: Prime Azelastine HCl Nasal Spray before initial use by releasing 4 sprays or until a fine mist appears. When Azelastine HCl Nasal Spray 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 into the eyes.

3 Dosage Forms And Strengths

Azelastine HCl Nasal Spray is a nasal spray . Each spray of Azelastine HCl Nasal Spray delivers a volume of 0.137 mL solution containing 137 mcg of azelastine hydrochloride, USP.

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 HCl 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 HCl Nasal Spray. Concurrent use of Azelastine HCl 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 HCl 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 Rhinitis Azelastine HCl Nasal Spray Two Sprays Per Nostril Twice Daily Adverse experience information for Azelastine HCl 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 HCl 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 HCl 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 HCl 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 HCl Nasal Spray 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 One Spray Per Nostril Twice Daily  Adverse experience information for Azelastine HCl 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 HCl 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 HCl 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 HCl 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 HCl Nasal Spray 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 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 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 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 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 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 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 (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 HCl 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 HCl 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 HCl 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 HCl Nasal Spray is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of Azelastine HCl 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 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 HCl 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 HCl 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 HCl 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 HCl 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 HCl Nasal Spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in young children. Accordingly, Azelastine HCl Nasal Spray should be kept out of the reach of children.

11 Description

Azelastine HCl Nasal Spray, 137 micrograms (mcg), 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 225°C and the pH of a saturated solution is between 5.0 and 5.4. Its chemical name is (±)-1-(2H)-phthalazinone,4-[(4chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride. Its molecular formula is C22H24ClN3O•HCl with the following chemical structure:Azelastine HCl Nasal Spray contains 0.1% azelastine hydrochloride, USP in an aqueous solution at pH 6.8 ± 0.3. It also contains benzalkonium chloride (125 mcg/mL), edetate disodium, hypromellose, citric acid, dibasic sodium phosphate, sodium chloride, and purified water. After priming [see Dosage and Administration (2.3)], each metered spray delivers a 0.137 mL mean volume containing 137 mcg of azelastine hydrochloride, USP (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 HCl 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 Electrophysiology:  In a placebo-controlled study (95 subjects with allergic rhinitis), there was no evidence of an effect of Azelastine HCl 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 to 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. 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 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 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 Cmax 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 coadministration 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 ngh/mL for azelastine, whereas, administration of azelastine alone resulted in Cmax of 5.57 ± 2.7 ng/mL and AUC of 48.4 ± 24 ngh/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 Cmax of 8.89 ±3.28 ng/mL and AUC of 88.22 ± 40.43 ngh/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 ngh/mL for azelastine. Theophylline: No significant pharmacokinetic interaction was observed with the coadministration 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 Daily  The efficacy and safety of Azelastine HCl Nasal Spray were evaluated in three placebo-controlled clinical trials of Azelastine HCl 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 HCl 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 HCl Nasal Spray 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  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  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  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 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 HCl 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 Daily The efficacy and safety of Azelastine HCl Nasal Spray were evaluated in two placebo-controlled clinical trials of Azelastine HCl 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 12hour 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 to3 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 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 One Spray Per Nostril Twice Daily Versus Placebo  Treatment  NBaseline LS Mean (SD)   Change from Baseline (SD) Treatment Difference P-value Trial 4: 12 Hour AM and PM Reflective TNSS    Azelastine HCl Nasal Spray  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  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 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 were evaluated in two placebo-controlled clinical trials of Azelastine HCl 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 HCl 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

Azelastine HCl Nasal Spray , 137 mcg is supplied as a 30-mL package (NDC 67877-477-50)  delivering 200 metered sprays in a high-density polyethylene (HDPE) bottle fitted with a metered-dose spray pump unit. The spray pump unit consists of a nasal spray pump fitted with a white safety clip and a transparent plastic dust cover. The net content of the bottle is 30 mL (net weight 30 gm of solution). Each bottle contains 30 mg (1 mg/mL) of azelastine hydrochloride, USP. After priming [see Dosage and Administration (2.3)], each spray delivers a fine mist containing a mean volume of 0.137 mL solution containing 137 mcg of azelastine hydrochloride, USP. The correct amount of medication in each spray cannot be assured before the initial priming and after 200 sprays have been used, even though the bottle is not completely empty. The bottle should be discarded after 200 sprays have been used. Azelastine HCl Nasal Spray should not be used after the expiration date “EXP” printed on the medicine label and carton. Storage:Store at controlled room temperature 20° to 25°C (68° to 77°F). Protect from freezing.

17 Patient Counseling Information

See FDA-approved patient labeling (Patient Information and Instructions for Use). Activities Requiring Mental Alertness  Somnolence has been reported in some patients taking Azelastine HCl 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 HCl Nasal Spray [see Warnings and Precautions (5.1)]. Concurrent Use of Alcohol and other Central Nervous System Depressants  Instruct patients to avoid concurrent use of Azelastine HCl 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 Reactions  Inform patients that the treatment with Azelastine HCL 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)]. Priming  Instruct patients to prime the pump before initial use and when Azelastine HCl Nasal Spray 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 into their eyes. Keep Out of Children's Reach  Instruct patients to keep Azelastine HCl Nasal Spray out of the reach of children. If a child accidentally ingests Azelastine HCl Nasal Spray, seek medical help or call a poison control center immediately.Manufactured By:Alkem Laboratories 1733 Gilsinn Lane, Fenton, MO 63026Manufactured for: Alkem Laboratories Ltd Mumbai - 400 013, INDIADistributed by: Ascend Laboratories, LLC Parsipanny, NJ 07054

Medication Guide

PATIENT INFORMATION Azelastine HCl Nasal Spray Important: For use in your nose only. What is Azelastine HCl Nasal Spray?  •                     Azelastine HCl Nasal Spray is a prescription medicine used to treat symptoms of seasonal allergic rhinitis in people age 5 and older and vasomotor rhinitis in people age 12 and older. •                     Azelastine HCl Nasal Spray may help to reduce your nasal symptoms including stuffy nose, runny nose, itching and sneezing. It is not known if Azelastine HCl Nasal Spray is safe and effective in children with seasonal allergic rhinitis under 5 years of age or in children with vasomotor rhinitis under 12 years of age.What should I tell my healthcare provider before using Azelastine HCl Nasal Spray ? Before using Azelastine HCl Nasal Spray , tell your healthcare provider if you are:  •                     allergic to any of the ingredients in Azelastine HCl Nasal Spray . See the end of this leaflet for a complete list of ingredients in Azelastine HCl Nasal Spray . •                     pregnant, or plan to become pregnant. It is not known if Azelastine HCl Nasal Spray will harm your unborn baby. •                     breastfeeding, or plan to breastfeed. It is not known if Azelastine HCl Nasal Spray passes into your breast milk. You and your healthcare provider should decide if you will use Azelastine HCl Nasal Spray 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 and other medicines may affect each other, causing side effects.How should I use Azelastine HCl Nasal Spray ?  •                     Read the Instructions for Use at the end of this leaflet for information about the right way to use Azelastine HCl Nasal Spray . •                     Spray Azelastine HCl Nasal Spray in your nose only. Do not spray it into your eyes or mouth. •                     Use Azelastine HCl Nasal Spray 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 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, call your healthcare provider or go to the nearest hospital emergency room right away.  What should I avoid while using Azelastine HCl Nasal Spray?  Azelastine HCl Nasal Spray can cause sleepiness:  •                     Do not drive, operate machinery, or do other dangerous activities until you know how Azelastine HCl Nasal Spray affects you. •                     Do not drink alcohol or take other medicines that may cause you to feel sleepy while using Azelastine HCl Nasal Spray. It may make your sleepiness worse. What are the possible side effects of Azelastine HCl Nasal Spray?  The most common side effects of Azelastine HCl Nasal Spray include: •                     unusual bitter taste •                     headache •                     sleepiness •                     nose burning, pain or discomfort •                     runny nose •                     scratchy or sore throat •                     nosebleeds •                     inflamation 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. 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?  •                     Keep Azelastine HCl Nasal Spray upright at 68°F to 77°F (20°C to 25°C). •                     Do not freeze Azelastine HCl Nasal Spray. •                     Do not use Azelastine HCl Nasal Spray after the expiration date “EXP” on the medicine label and box. Keep Azelastine HCl Nasal Spray and all medicines out of reach of children.  General information about the safe and effective use of Azelastine HCl Nasal Spray.  Medicines are sometimes prescribed for conditions other than those listed in a Patient Information leaflet. Do not use Azelastine HCl Nasal Spray for a condition for which it was not prescribed. Do not give Azelastine HCl Nasal Spray 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. 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 that is written for health professionals. For more information call 1-877-ASC-RX01 (877-272-7901). What are the ingredients in Azelastine HCl Nasal Spray?  Active ingredient: azelastine hydrochloride,USP. Inactive ingredients: benzalkonium chloride, edetate disodium, hypromellose, citric acid, dibasic sodium phosphate, sodium chloride, and purified water.

Instructions For Use

Instructions for UseAzelastine HCl Nasal SprayImportant:For use in your nose only.For the correct dose of medicine:  •                     Keep your head tilted downward when spraying into your nostril. •                     Change nostrils each time you use the spray. •                     Breathe gently and do not tip your head back after using the spray. This will keep the medicine from running down into your throat. You may get a bitter taste in your mouth. Figure A identifies the parts of your Azelastine HCL Nasal Spray pumpFigure A  Before you use Azelastine HCL Nasal Spray for the first time, you will need to prime the bottle. Priming your Azelastine HCL Nasal Spray)   Remove the transparent  dust cover over the tip of the pump and the white safety clip just under the “shoulders” of the pump (See Figure B). Figure BHold the bottle upright with 2 fingers on the shoulders of the spray pump unit and •                     put your thumb on the bottom of the bottle. Press upward with your thumb and release for the pumping action. Repeat this until you see a fine mist (See Figure C). •                     To get a fine mist you must pump the spray fast and use firm pressure against the bottom of the bottle. If you see a stream of liquid, the pump is not working correctly and you may have nasal discomfort. •                     This should happen in 4 sprays or less. Now your pump is primed and ready to use. Figure C•                     Do not use Azelastine HCL Nasal Spray unless you see a fine mist after you do the priming sprays. If you do not see a fine mist, clean the tip of the spray nozzle. See the “Cleaning the Spray Tip of your Azelastine HCL Nasal Spray ” section below. •                     If you do not use Azelastine Hydrochloride Nasal Solution (Nasal Spray) for 3 or more days, you will need to prime the pump with 2 sprays or until you see a fine mist. Using your Azelastine HCL Nasal Spray) Step 1. Blow your nose to clear your nostrils. Step 2. Keep your head tilted downward toward your toes. Step 3. Place the spray tip about ¼ inch to ½ inch into 1 nostril. Hold bottle upright and aim the spray tip toward the back of your nose (See Figure D).Figure DStep 4. Close your other nostril with a finger. Press the pump 1 time and sniff gently at the same time, keeping your head tilted forward and down (See Figure E).Figure EStep 5. Repeat Step 3 and Step 4 in your other nostril.Step 6. If your healthcare provider tells you to use 2 sprays in each nostril, repeat Steps 2               through 4 above for the second spray in each nostril.  Step 7. Breathe in gently, and do not tilt your head back after using Azelastine HCL Nasal Spray . This will help to keep the medicine from going into your throat. Step 8. When you finish using your Azelastine HCL Nasal Spray , wipe the spray tip with a clean tissue or cloth. Put the safety clip and dust cover back on the bottle. Cleaning the Spray Tip of your Azelastine HCL Nasal Spray•                     If the spray tip opening is clogged, do not use a pin or pointed object to unclog the tip. Unscrew the spray pump unit from the bottle by turning it to the left (counter-clockwise) (See Figure F). •                     Soak only the spray pump unit in warm water. Squirt the spray unit several times while holding it under water. Use the pumping action to clear the opening in the tip (See Figure G).                                                                                                  Figure F                                                              Figure G•                     Let the spray pump unit air dry. Make sure it is dry before you put it back onto the bottle. •                     Put the spray pump unit back into the open bottle and tighten it by turning clockwise (to the right). •                     To keep the medicine from leaking out, use firm pressure when you put the pump back onto the bottle. •                     After cleaning, follow the instructions for priming. This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured By:Alkem Laboratories 1733 Gilsinn Lane, Fenton, MO 63026 Manufactured for: Alkem Laboratories LtdMumbai - 400 013, INDIA Distributed by:Ascend Laboratories, LLCParsippany, NJ 07054 PT 2385 Revised: 07/2017

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