Astepro Information
Astepro (Azelastine) Dosage And Administration
Administer Astepro (Azelastine) Nasal Spray by the intranasal route only.
Priming
Astepro (Azelastine) Dosage Forms And Strengths
Astepro (Azelastine) Nasal Spray is a nasal spray solution. Each spray of Astepro (Azelastine) Nasal Spray 0.1% delivers a volume of 0.137 mL solution containing 137 mcg of azelastine hydrochloride. Each spray of Astepro (Azelastine) Nasal Spray 0.15% delivers a volume of 0.137 mL solution containing 205.5 mcg of azelastine hydrochloride.
Astepro (Azelastine) Contraindications
Astepro (Azelastine) Adverse Reactions
Use of Astepro (Azelastine) Nasal Spray has been associated with somnolence [].
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.
Astepro (Azelastine) Nasal Spray 0.1%
®
Adults and Adolescents 12 Years of Age and Older
Table 1 contains adverse reactions reported with frequencies greater than or equal to 2% and more frequently than placebo in patients treated with Astepro (Azelastine) Nasal Spray 0.1% in the controlled clinical trial described above.
Long-Term (12 Month) Safety Trial:
Astepro (Azelastine) Nasal Spray 0.15%
Adults and Adolescents 12 Years of Age and Older
Table 2 contains adverse reactions reported with frequencies greater than or equal to 2% and more frequently than placebo in patients treated with Astepro (Azelastine) Nasal Spray 0.15% in the seasonal and perennial allergic rhinitis controlled clinical trials.
In the above trials, somnolence was reported in
Long-Term (12 Month) Safety Trial:
During the post approval use of Astepro (Azelastine) Nasal Spray 0.1% and 0.15%, 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: abdominal pain, nasal burning, nausea, sweet taste, and throat irritation.
Additionaly, the following adverse reactions have been identified during the post approval use of the Astelin brand of azelastine hydrochloride 0.1% nasal spray (total daily dose 0.55 mg to 1.1 mg). 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 the following: anaphylactoid reaction, application site irritation, atrial fibrillation, blurred vision, chest pain, confusion, dizziness, dyspnea, facial edema, hypertension, involuntary muscle contractions, nervousness, palpitations, paresthesia, parosmia, paroxysmal sneezing, pruritus, rash, disturbance or loss of sense of smell and/or taste, tachycardia, tolerance, urinary retention, and xerophthalmia.
Astepro (Azelastine) Use In Specific Populations
Pregnancy Category C
Teratogenic Effects
2
In rats, azelastine hydrochloride caused malformations (oligo- and brachydactylia), delayed ossification and skeletal variations, in the absence of maternal toxicity, at an oral dose approximately 150 times the MRHDID in adults on a mg/m basis. At a dose approximately 340 times the MRHDID, azelastine hydrochloride also caused embryo-fetal death and decreased fetal weight; however, this dose caused severe maternal toxicity. Neither fetal nor maternal effects occurred at a dose approximately 15 times the MRHDID.
In rabbits, azelastine hydrochloride caused abortion, delayed ossification and decreased fetal weight at oral doses approximately 300 times the MRHDID in adults on a mg/m basis; however, these doses also resulted in severe maternal toxicity. Neither fetal nor maternal effects occurred at a dose approximately 3 times the MRHDID.
Astepro (Azelastine) Overdosage
There have been no reported overdosages with Astepro (Azelastine) Nasal Spray. Acute overdosage by adults with this dosage form is unlikely to result in clinically significant adverse events, other than increased somnolence, since one 30-mL bottle of Astepro (Azelastine) Nasal Spray 0.1% contains up to 30 mg of azelastine hydrochloride and one 30-mL bottle of Astepro (Azelastine) Nasal Spray 0.15% contains up to 45 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 events. General supportive measures should be employed if overdosage occurs. There is no known antidote to Astepro (Azelastine) Nasal Spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in children. Accordingly, Astepro (Azelastine) Nasal Spray should be kept out of the reach of children. Oral doses of 120 mg/kg and greater (approximately 300 times the maximum recommended human daily intranasal dose [MRHDID] in adults and children on a mg/m basis) were lethal in mice. Responses seen prior to death were tremor, convulsions, decreased muscle tone, and salivation. In dogs, single oral doses as high as 10 mg/kg (approximately 160 times the MRHDID in adults and children on a mg/m basis) were well tolerated, but single oral doses of 20 mg/kg were lethal.
Astepro (Azelastine) Description
Astepro (Azelastine) (azelastine hydrochloride) Nasal Spray 0.1%, 137 micrograms (mcg), is an antihistamine formulated as a metered-spray solution for intranasal administration. Astepro (Azelastine) (azelastine hydrochloride) Nasal Spray 0.15%, 205.5 micrograms (mcg), is 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-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride. Its molecular formula is CHClNO•HCl with the following chemical structure:
Astepro (Azelastine) Nasal Spray 0.1% contains 0.1% azelastine hydrochloride in an isotonic aqueous solution containing sorbitol, sucralose, hypromellose, sodium citrate, edetate disodium, benzalkonium chloride (125 mcg/mL), and purified water (pH 6.4).
After priming [], each metered spray delivers a 0.137 mL mean volume containing 137 mcg of azelastine hydrochloride (equivalent to 125 mcg of azelastine base). The 30-mL (net weight 30 gm of solution) bottle provides 200 metered sprays.
Astepro (Azelastine) Nasal Spray 0.15% contains 0.15% azelastine hydrochloride in an isotonic aqueous solution containing sorbitol, sucralose, hypromellose, sodium citrate, edetate disodium, benzalkonium chloride (125 mcg/mL), and purified water (pH 6.4).
After priming [], each metered spray delivers a 0.137 mL mean volume containing 205.5 mcg of azelastine hydrochloride (equivalent to 187.6 mcg of azelastine base). The 30-mL (net weight 30 gm of solution) bottle provides 200 metered sprays.
Astepro (Azelastine) Clinical Pharmacology
Cardiac Effects:
Interaction studies investigating the cardiac repolarization effects of concomitantly administered oral azelastine hydrochloride and erythromycin or ketoconazole were conducted. Oral erythromycin had no effect on azelastine pharmacokinetics or QTc based on analysis of serial electrocardiograms. Ketoconazole interfered with the measurement of azelastine plasma levels; however, no effects on QTc were observed [].
Absorption
Metabolism
Elimination
Special Populations
Hepatic Impairment
Renal Impairment
max
Age
Gender
Race
Drug-Drug Interactions
Theophylline
Astepro (Azelastine) Nonclinical Toxicology
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/m 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/m basis). At 68.6 mg/kg (approximately 340 times the MRHDID on a mg/m 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.
Reproductive Toxicology Studies
Azelastine hydrochloride has been shown to cause developmental toxicity. Treatment of mice with an oral dose of 68.6 mg/kg (approximately 170 times the maximum recommended human daily intranasal dose [MRHDID] on a mg/m basis) caused embryo-fetal death, malformations (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification, and decreased fetal weight. This dose also caused maternal toxicity as evidenced by decreased body weight. Neither fetal nor maternal effects occurred at a dose of 3 mg/kg (approximately 7 times the MRHDID on a mg/m basis).
In rats, an oral dose of 30 mg/kg (approximately 150 times the MRHDID on a mg/m basis) caused malformations (oligo-and brachydactylia), delayed ossification and skeletal variations, in the absence of maternal toxicity. At 68.6 mg/kg (approximately 340 times the MRHDID on a mg/m basis) azelastine hydrochloride also caused embryo-fetal death and decreased fetal weight; however, the 68.6 mg/kg dose caused severe maternal toxicity. Neither fetal nor maternal effects occurred at a dose of 3 mg/kg (approximately 15 times the MRHDID on a mg/m basis).
In rabbits, oral doses of 30 mg/kg and greater (approximately 300 times the MRHDID on a mg/m basis) caused abortion, delayed ossification and decreased fetal weight; however, these doses also resulted in severe maternal toxicity. Neither fetal nor maternal effects occurred at a dose of 0.3 mg/kg (approximately 3 times the MRHDID on a mg/m basis).
Astepro (Azelastine) Clinical Studies
Astepro (Azelastine) Nasal Spray 0.1%
The efficacy and safety of Astepro (Azelastine) Nasal Spray 0.1% was evaluated in a 2-week, randomized, multicenter, double-blind, placebo-controlled clinical trial including 834 adult and adolescent patients 12 years of age and older with symptoms of seasonal allergic rhinitis. The population was 12 to 83 years of age (60% female, 40% male; 69% white, 16% black, 12% Hispanic, 2% Asian, 1% other).
Patients were randomized to one of six treatment groups: 1 spray per nostril of either Astepro (Azelastine) Nasal Spray 0.1%, Astelin (azelastine hydrochloride) Nasal Spray or vehicle placebo twice daily; or 2 sprays per nostril of Astepro (Azelastine) Nasal Spray 0.1%, Astelin (azelastine hydrochloride) Nasal Spray or vehicle placebo twice daily.
Assessment of efficacy was based on the 12-hour reflective total nasal symptom score (rTNSS) assessed daily in the morning and evening, in addition to the instantaneous total nasal symptom score (iTNSS) and other supportive secondary efficacy variables. TNSS is calculated as the sum of the patients’ scoring of the four individual nasal symptoms (rhinorrhea, nasal congestion, sneezing, and nasal itching) on a 0 to 3 categorical severity scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The rTNSS required patients to record symptom severity over the previous 12 hours. For the primary efficacy endpoint, the mean change from baseline rTNSS, morning (AM) and evening (PM) rTNSS scores were summed for each day (maximum score of 24) and then averaged over the 2 weeks. The iTNSS, recorded immediately prior to the next dose, were assessed as an indication of whether the effect was maintained over the dosing interval.
In this trial, Astepro (Azelastine) Nasal Spray 0.1% two sprays twice a day demonstrated a greater decrease in rTNSS and iTNSS than placebo and the difference was statistically significant. The trial results are presented in Table 3 (Trial 1).
The efficacy of Astepro (Azelastine) Nasal Spray 0.1% one spray per nostril twice daily for seasonal allergic rhinitis is supported by two, 2-week, placebo-controlled clinical trials with Astelin (azelastine hydrochloride) Nasal Spray in 413 patients with seasonal allergic rhinitis. In these trials, efficacy was assessed using the TNSS (described above). Astelin Nasal Spray demonstrated a greater decrease from baseline in the summed AM and PM rTNSS compared with placebo and the difference was statistically significant.
Astepro (Azelastine) Nasal Spray 0.15%
The efficacy and safety of Astepro (Azelastine) Nasal Spray 0.15% in seasonal allergic rhinitis was evaluated in five randomized, multicenter, double-blind, placebo-controlled clinical trials in 2499 adult and adolescent patients 12 years and older with symptoms of seasonal allergic rhinitis (Trials 2, 3, 4, 5, and 6). The population of the trials was 12 to 83 years of age (64% female, 36% male; 81% white, 12% black,
Two 2-week seasonal allergic rhinitis trials evaluated the efficacy of Astepro (Azelastine) Nasal Spray 0.15% dosed at 2 sprays twice daily. The first trial (Trial 2) compared the efficacy of Astepro (Azelastine) Nasal Spray 0.15% and Astelin (azelastine hydrochloride) Nasal Spray to vehicle placebo. The other trial (Trial 3) compared the efficacy of Astepro (Azelastine) Nasal Spray 0.15% and Astepro (Azelastine) Nasal Spray 0.1% to vehicle placebo. In these two trials, Astepro (Azelastine) Nasal Spray 0.15% demonstrated greater decreases in rTNSS than placebo and the differences were statistically significant (Table 3).
Three 2-week seasonal allergic rhinitis trials evaluated the efficacy of Astepro (Azelastine) Nasal Spray 0.15% dosed at 2 sprays once daily compared to the vehicle placebo. Trial 4 demonstrated a greater decrease in rTNSS than placebo and the difference was statistically significant (Table 3). Trial 5 and Trial 6 were conducted in patients with Texas mountain cedar allergy. In Trial 5 and Trial 6, Astepro (Azelastine) Nasal Spray 0.15% demonstrated a greater decrease in rTNSS than placebo and the differences were statistically significant (Trials 5 and 6; Table 3). Instantaneous TNSS results for the once daily dosing regimen of Astepro (Azelastine) Nasal Spray 0.15% are shown in . In Trials 5 and 6, Astepro (Azelastine) Nasal Spray 0.15% demonstrated a greater decrease in iTNSS than placebo and the differences were statistically significant.
Astepro (Azelastine) Nasal Spray 0.15% at a dose of 1 spray twice daily was not studied. The Astepro (Azelastine) Nasal Spray 0.15% 1 spray twice daily dosing regimen is supported by previous findings of efficacy for Astelin (azelastine hydrochloride) Nasal Spray and a favorable comparison of Astepro (Azelastine) Nasal Spray 0.15% to Astelin Nasal Spray and Astepro (Azelastine) Nasal Spray 0.1% (Table 3).
Astepro (Azelastine) Nasal Spray 0.15%
The efficacy and safety of Astepro (Azelastine) Nasal Spray 0.15% in perennial allergic rhinitis was evaluated in one randomized, multicenter, double-blind, placebo-controlled clinical trial in 578 adult and adolescent patients 12 years and older with symptoms of perennial allergic rhinitis. The population of the trial was 12 to 84 years of age (68% female, 32% male; 85% white, 11% black, 1% Asian, 3% other; 17% Hispanic, 83% non-Hispanic).
Assessment of efficacy was based on the 12-hour reflective total nasal symptom score (rTNSS) assessed daily in the morning and evening, the instantaneous total nasal symptom score (iTNSS), and other supportive secondary efficacy variables. The primary efficacy endpoint was the mean change from baseline rTNSS over 4 weeks. The one 4-week perennial allergic rhinitis trial evaluated the efficacy of Astepro (Azelastine) Nasal Spray 0.15%, Astepro (Azelastine) Nasal Spray 0.1%, and vehicle placebo dosed at 2 sprays per nostril twice daily. In this trial, Astepro (Azelastine) Nasal Spray 0.15% demonstrated a greater decrease in rTNSS than placebo and the difference was statistically significant (Table 5).
Astepro (Azelastine) How Supplied/storage And Handling
Astepro (Azelastine) (azelastine hydrochloride) Nasal Spray 0.1% (NDC 0037-0242-30) is supplied as a 30-mL package 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 blue safety clip and a blue 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. After priming [], each spray delivers a fine mist containing a mean volume of 0.137 mL solution containing 137 mcg of azelastine hydrochloride. 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.
Astepro (Azelastine) (azelastine hydrochloride) Nasal Spray 0.15% is supplied as a 30-mL package (NDC 0037-0243-30) 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 blue safety clip and a blue plastic dust cover. The net content of the bottle is 30 mL (net weight 30 gm of solution). The 30-mL bottle contains 45 mg (1.5 mg/mL) of azelastine hydrochloride. After priming [], each spray delivers a fine mist containing a mean volume of 0.137 mL solution containing 205.5 mcg of azelastine hydrochloride. The correct amount of medication in each spray cannot be assured before the initial priming and after 200 sprays for the 30-mL bottle have been used, even though the bottle is not completely empty. The bottle should be discarded after 200 sprays have been used.
Astepro (Azelastine) Nasal Spray 0.1% and 0.15% should not be used after the expiration date “EXP” printed on the medicine label and carton.
Astepro (Azelastine) Patient Counseling Information
Patients should be instructed to use Astepro (Azelastine) Nasal Spray only as prescribed. For the proper use of the nasal spray and to attain maximum improvement, the patient should read and follow carefully the accompanying FDA-Approved Patient Labeling.
Astepro (Azelastine)
Astepro (Azelastine)
Astepro (Azelastine)
