azelastine HCl 137 MCG/ACTUAT Metered Dose Nasal Spray
DRUG INTERACTIONS
7 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 )].
OVERDOSAGE
10 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.
DESCRIPTION
11 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 g/mol .
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 C 22 H 24 ClN 3 O•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.
CLINICAL STUDIES
14 14.1 Seasonal Allergic Rhinitis Two Sprays Per Nostril Twice Daily The 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 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 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 Daily The 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 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 hydrochloride 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 hydrochloride 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 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.
HOW SUPPLIED
16 / STORAGE AND HANDLING Product: 50090-2330
DOSAGE FORMS AND STRENGTHS
3 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.
Azelastine hydrochloride nasal spray: 137 mcg of azelastine hydrochloride in each 0.137 mL spray.
( 3 )
INDICATIONS AND USAGE
1 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.
Azelastine hydrochloride nasal spray is an H1-receptor antagonist 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.
( 1 )
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Somnolence: Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking azelastine hydrochloride nasal spray.
( 5.1 ) Alcohol and other central nervous system (CNS) depressants: Avoid concurrent use with azelastine hydrochloride nasal spray because further decreased alertness and impairment of CNS performance may occur.
( 5.1 ) 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 )] .
INFORMATION FOR PATIENTS
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 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 Depressants Instruct 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 Reactions Inform 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)].
Priming Instruct 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 Eyes Instruct patients to avoid spraying azelastine hydrochloride nasal spray into their eyes.
Keep Out of Children’s Reach Instruct 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 SPRAY 137 mcg Manufactured by Manufactured for Apotex Inc.
Apotex Corp.
Toronto, Ontario Weston, Florida Canada M9L 1T9 33326 Revised: September 2018
DOSAGE AND ADMINISTRATION
2 For intranasal use only ( 2.3 ) Seasonal allergic rhinitis: Pediatric patients 5 to 11 years of age: 1 spray per nostril twice daily ( 2.1 ) Adults and adolescents 12 years of age and older: 1 or 2 sprays per nostril twice daily ( 2.1 ) Vasomotor rhinitis: 2 sprays per nostril twice daily in adults and adolescents 12 years of age and older ( 2.2 ) Prime azelastine hydrochloride nasal spray before initial use and when it has not been used for 3 or more days ( 2.3 ) 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.