Azelastine Hydrochloride

AZELASTINE HYDROCHLORIDE- azelastine hydrochloride spray, metered
Apotex Corp.

FigureG

1 INDICATIONS AND USAGE

1.1 Allergic Rhinitis

Azelastine hydrochloride nasal spray, 0.15% is indicated for the relief of the symptoms of seasonal allergic rhinitis in patients 6 years of age and older and perennial allergic rhinitis in patients 6 years of age and older.

2 DOSAGE AND ADMINISTRATION

2.1 Seasonal Allergic Rhinitis

Children 6 to 11 years of age: azelastine hydrochloride nasal spray, 0.15%, 1 spray per nostril twice daily.

Adults and adolescents 12 years of age and older: azelastine hydrochloride nasal spray, 0.15%, 1 or 2 sprays per nostril twice daily. Azelastine hydrochloride nasal spray, 0.15% may also be administered as 2 sprays per nostril once daily.

2.2 Perennial Allergic Rhinitis

Children 6 to 11 years of age: azelastine hydrochloride nasal spray, 0.15%, 1 spray per nostril twice daily.

Adults and adolescents 12 years of age and older: azelastine hydrochloride nasal spray, 0.15%, 2 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 6 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 available in one dosage strength:

• Each spray of azelastine hydrochloride nasal spray 0.15% delivers a volume of 0.137 mL solution containing 205.5 mcg of azelastine hydrochloride.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 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.

Azelastine hydrochloride nasal spray, 0.15%
The safety data described below reflect exposure to azelastine hydrochloride nasal spray, 0.15% in 2114 patients (6 months of age and older) with seasonal or perennial allergic rhinitis from 10 clinical trials of 2 weeks to 12 months duration. In 8 double-blind, placebo-controlled clinical trials of 2 to 4 weeks duration, 1703 patients (646 males and 1059 females) with seasonal or perennial allergic rhinitis were treated with azelastine hydrochloride nasal spray, 0.15% one or two sprays per nostril once or twice daily. In the 12 month open-label, active-controlled clinical trial, 466 patients (156 males and 310 females) with perennial allergic rhinitis were treated with azelastine hydrochloride nasal spray, 0.15% two sprays per nostril twice daily. Of these 466 patients, 152 had participated in the 4-week placebo-controlled perennial allergic rhinitis clinical trials. In a 4-week, double-blind, placebo-controlled clinical trial, 161 patients (87 males and 74 females) ages 6 to 11 years of age with perennial allergic rhinitis, with or without concomitant seasonal allergic rhinitis, were treated with azelastine hydrochloride nasal spray, 0.15% one spray per nostril twice daily. In a 4-week clinical trial, 95 patients (59 males and 36 females) ages 6 months to 5 years of age with seasonal and/ or perennial allergic rhinitis were treated with azelastine hydrochloride nasal spray, 0.15% one spray per nostril twice daily. The racial distribution for the 10 clinical trials was 79% white, 14% black, 2% Asian, and 5% other.

Adults and Adolescents 12 Years of Age and OlderIn the 7 placebo controlled clinical trials of 2 to 4 week duration, 2343 patients with seasonal allergic rhinitis and 540 patients with perennial allergic rhinitis were treated with two sprays per nostril of either azelastine hydrochloride nasal spray, 0.15% or placebo once or twice daily. Overall, adverse reactions were more common in the azelastine hydrochloride nasal spray, 0.15% treatment groups (16 to 31%) than in the placebo groups (11 to 24%). Overall, less than 2% of patients discontinued due to adverse reactions and withdrawal due to adverse reactions was similar among the treatment groups.

Table 3 contains adverse reactions reported with frequencies greater than or equal to 2% and more frequently than placebo in patients treated with azelastine hydrochloride nasal spray, 0.15% in the seasonal and perennial allergic rhinitis controlled clinical trials.

Table 3. Adverse Reactions with ≥2% Incidence in Placebo-Controlled Trials of 2 to 4 Weeks’ Duration with Azelastine Hydrochloride Nasal Spray, 0.15% in Adult and Adolescent Patients with Seasonal or Perennial Allergic Rhinitis

	2 sprays twice daily		2 sprays once daily
	Azelastine Hydrochloride Nasal Spray, 0.15%(N=523)	Vehicle Placebo (N=523)	Azelastine Hydrochloride Nasal Spray, 0.15% (N=1021)	Vehicle Placebo (N=816)
Bitter Taste	31 (6%)	5 (1%)	38 (4%)	2 (<1%)
Nasal Discomfort	18 (3%)	12 (2%)	37 (4%)	7 (1%)
Epistaxis	5 (1%)	7 (1%)	21 (2%)	14 (2%)
Sneezing	9 (2%)	1 (<1%)	14 (1%)	0 (0%)

In the above trials, somnolence was reported in <1% of patients treated with azelastine hydrochloride nasal spray, 0.15% (11 of 1544) or vehicle placebo (1 of 1339).

Long-Term (12 Month) Safety Trial
In the 12 month, open-label, active-controlled, long-term safety trial, 466 patients (12 years of age and older) with perennial allergic rhinitis were treated with azelastine hydrochloride nasal spray, 0.15% two sprays per nostril twice daily and 237 patients were treated with mometasone nasal spray two sprays per nostril once daily. The most frequently reported adverse reactions (>5%) with azelastine hydrochloride nasal spray, 0.15% were bitter taste, headache, sinusitis, and epistaxis. Focused nasal examinations were performed and no nasal ulcerations or septal perforations were observed. In each treatment group, approximately 3% of patients had mild epistaxis. No patients had reports of severe epistaxis. Fifty-four patients (12%) treated with azelastine hydrochloride nasal spray, 0.15% and 17 patients (7%) treated with mometasone nasal spray discontinued from the trial due to adverse events.