AZELASTINE HYDROCHLORIDE

AZELASTINE HYDROCHLORIDE- azelastine hydrochloride spray, metered
Bryant Ranch Prepack

Chemical StructureFigure AFigure BFigure CFigure DFigure EFigure FFigure G

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 DOSAGE AND ADMINISTRATION

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 WARNINGS AND PRECAUTIONS

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 Rhinitis

Azelastine Hydrochloride Nasal Spray Two Sprays Per Nostril Twice Daily

Adverse 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 = 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 Hydrochloride Nasal Spray One Spray Per Nostril Twice Daily

Adverse 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 Daily

The 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.

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 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 = 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 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.