Azelastine Explained

Verifiedrevid:458613328
Width:150
Width2:200
Tradename:Astelin, others
Dailymedid:Azelastine
Pregnancy Au:B3
Routes Of Administration:Eye drops, nasal spray, by mouth
Atc Prefix:R01
Atc Suffix:AC03
Atc Supplemental:,
Legal Au:S2
Legal Uk:POM
Legal Us:Rx Only
Legal Us Comment:/ OTC
Bioavailability:40% (intranasal)
Metabolites:desmethylazelastine (active)
Onset:Within 1 hour [1]
Elimination Half-Life:22 hours
Duration Of Action:12 hours
Index2 Label:as HCl
Cas Number:58581-89-8
Cas Number2:79307-93-0
Pubchem:2267
Pubchem2:54360
Iuphar Ligand:7121
Drugbank:DB00972
Drugbank2:DBSALT000013
Chemspiderid:2180
Chemspiderid2:49103
Unii:ZQI909440X
Unii2:0L591QR10I
Kegg:D07483
Kegg2:D00659
Chebi:2950
Chebi2:2951
Chembl:639
Chembl2:1200809
Iupac Name:(RS)-4-[(4-Chlorophenyl)methyl]-2-(1-methylazepan-4-yl)-phthalazin-1-one
C:22
H:24
Cl:1
N:3
O:1
Smiles:Clc1ccc(cc1)CC\3=N\N(C(=O)c2ccccc2/3)C4CCCN(C)CC4
Stdinchi:1S/C22H24ClN3O/c1-25-13-4-5-18(12-14-25)26-22(27)20-7-3-2-6-19(20)21(24-26)15-16-8-10-17(23)11-9-16/h2-3,6-11,18H,4-5,12-15H2,1H3
Stdinchikey:MBUVEWMHONZEQD-UHFFFAOYSA-N

Azelastine, sold under the brand name Astelin among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis.[2] [3] Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose.[4] Effects last for up to 12 hours.[4]

Common side effects include headache, sleepiness, change in taste, and sore throat.[4] It is unclear if use is safe during pregnancy or breastfeeding.[5] It is a second-generation antihistamine and works by blocking the release of a number of inflammatory mediators including histamine.[6] [4]

Azelastine was patented in 1971 and came into medical use in 1986.[7] It is available as a generic medication.[8] [9] In 2021, it was the 145th most commonly prescribed medication in the United States, with more than 4million prescriptions.[10] [11]

Medical uses

Azelastine nasal spray is indicated for the local treatment of the symptoms of seasonal allergic rhinitis and perennial allergic rhinitis, such as rhinorrhea, sneezing and nasal pruritus in people five years of age and older.[12] [13] [14] In some countries, it is also indicated for the treatment of vasomotor rhinitis in adults and children ≥ 12 years old. Azelastine eye drops are indicated for the local treatment of seasonal and perennial allergic conjunctivitis.[15] [16]

Side effects

Azelastine is safe and well tolerated in both adults and children with allergic rhinitis.[17] [18] [19] Bitter taste, headache, nasal burning and somnolence are the most frequently reported adverse events. US prescribing recommendations warn against the concurrent use of alcohol and/or other central nervous system depressants, but to date there have been no studies to assess the effects of azelastine nasal spray on the CNS in humans. More recent studies[20] [21] have shown similar degrees of somnolence (approx. 2%) compared with placebo treatment.

The most common side effect is a bitter taste (about 20% of people). Due to this, the manufacturer has produced another formulation of azelastine with sucralose.[22] The problem of bitter taste may also be reduced by correct application of the nasal spray (i.e. slightly tipping the head forward and not inhaling the medication too deeply), or alternatively using the azelastine/sucralose formulation.[23]

In addition, anosmia (loss in the ability to smell) can occur with nasal spray antihistamines (including both formulations of azelastine).

Pharmacology

Pharmacodynamics

Azelastine has a triple mode of action:

  1. Anti-histamine effect,
  2. Mast-cell stabilizing effect and
  3. Anti-inflammatory effect.

Pharmacokinetics

The systemic bioavailability of azelastine is approximately 40% when administered intranasally.[1] Maximum plasma concentrations (Cmax) are observed within 2–3 hours.[1] The elimination half life, steady-state volume of distribution and plasma clearance are 22 h, 14.5 L/kg and 0.5 L/h/kg respectively (based on intravenous and oral administration data). Approximately 75% of an oral dose is excreted in feces. Pharmacokinetics of orally administered azelastine is not affected by age, gender, or hepatic impairment.

Metabolism

Azelastine is oxidatively metabolized by the cytochrome P450 family into its active metabolite, desmethylazelastine, and two inactive carboxylic acid metabolites.[24]

Chemical properties

The chemical nomenclature of azelastine is (±)-1-(2H)-phthalazinone, 4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-monohydrochloride. It is white, almost odorless with a bitter taste.[25]

Notes and References

  1. Book: Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ . Clinical Immunology . Antihistamines . Elsevier . 2008 . 10.1016/b978-0-323-04404-2.10089-2 . 1317–1329 . 9780323044042 . After intranasal administration, its systemic bioavailability is approximately 40%. Azelastine has an onset of action within the first hour of administration and reaches peak activity at 1–3 hours after administration. Duration of activity is about 12 hours. Intranasal administration results in maximal plasma concentrations in 2–3 hours. ... The half-life of the parent compound is 22 hours ....
  2. Book: British national formulary : BNF 76. 2018. Pharmaceutical Press. 9780857113382. 1169. 76.
  3. Book: Al-Ahmad M, Hassab M, Al Ansari A . Textbook of Clinical Otolaryngology . Allergic and Non-allergic Rhinitis . Springer International Publishing . Cham . 21 December 2020 . 978-3-030-54087-6 . 10.1007/978-3-030-54088-3_22 . 241–252 . 234142758 .
  4. Web site: Azelastine Hydrochloride Monograph for Professionals . Drugs.com . American Society of Health-System Pharmacists .
  5. Web site: Azelastine ophthalmic (Optivar) Use During Pregnancy . Drugs.com . 26 March 2019 .
  6. Book: Aronson JK . Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions . 2015 . Elsevier . 9780444537164 . 782 .
  7. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 548 .
  8. FDA Approves a Nasal Antihistamine for Nonprescription Use . U.S. Food and Drug Administration (FDA) . 17 June 2021 . 21 June 2021.
  9. Web site: First Generic Drug Approvals . U.S. Food and Drug Administration (FDA) . 8 July 2024 . 9 July 2024.
  10. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  11. Web site: Azelastine - Drug Usage Statistics . ClinCalc . 14 January 2024.
  12. Bousquet J, Schünemann HJ, Togias A, Bachert C, Erhola M, Hellings PW, Klimek L, Pfaar O, Wallace D, Ansotegui I, Agache I, Bedbrook A, Bergmann KC, Bewick M, Bonniaud P, Bosnic-Anticevich S, Bossé I, Bouchard J, Boulet LP, Brozek J, Brusselle G, Calderon MA, Canonica WG, Caraballo L, Cardona V, Casale T, Cecchi L, Chu DK, Costa EM, Cruz AA, Czarlewski W, D'Amato G, Devillier P, Dykewicz M, Ebisawa M, Fauquert JL, Fokkens WJ, Fonseca JA, Fontaine JF, Gemicioglu B, van Wijk RG, Haahtela T, Halken S, Ierodiakonou D, Iinuma T, Ivancevich JC, Jutel M, Kaidashev I, Khaitov M, Kalayci O, Kleine Tebbe J, Kowalski ML, Kuna P, Kvedariene V, La Grutta S, Larenas-Linnemann D, Lau S, Laune D, Le L, Lieberman P, Lodrup Carlsen KC, Lourenço O, Marien G, Carreiro-Martins P, Melén E, Menditto E, Neffen H, Mercier G, Mosgues R, Mullol J, Muraro A, Namazova L, Novellino E, O'Hehir R, Okamoto Y, Ohta K, Park HS, Panzner P, Passalacqua G, Pham-Thi N, Price D, Roberts G, Roche N, Rolland C, Rosario N, Ryan D, Samolinski B, Sanchez-Borges M, Scadding GK, Shamji MH, Sheikh A, Bom AT, Toppila-Salmi S, Tsiligianni I, Valentin-Rostan M, Valiulis A, Valovirta E, Ventura MT, Walker S, Waserman S, Yorgancioglu A, Zuberbier T . Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence . The Journal of Allergy and Clinical Immunology . 145 . 1 . 70–80.e3 . January 2020 . 31627910 . 10.1016/j.jaci.2019.06.049 . 10400.17/3723 . free .
  13. Web site: Rhinolast Nasal Spray Summary of Product Characteristics . Oct 2009 . 27 April 2010 .
  14. Web site: Astelin- azelastine hydrochloride spray, metered .
  15. Web site: Optilast Eye Drops Summary of Product Characteristics . Jan 2010 . 27 April 2010 .
  16. Web site: Optivar- azelastine hydrochloride solution/ drops .
  17. McNeely W, Wiseman LR . Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis . Drugs . 56 . 1 . 91–114 . July 1998 . 9664202 . 10.2165/00003495-199856010-00011 . 46956783 .
  18. Ratner PH, Findlay SR, Hampel F, van Bavel J, Widlitz MD, Freitag JJ . A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis . The Journal of Allergy and Clinical Immunology . 94 . 5 . 818–25 . November 1994 . 7963150 . 10.1016/0091-6749(94)90148-1.
  19. LaForce C, Dockhorn RJ, Prenner BM . Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial . Annals of Allergy, Asthma & Immunology . 76 . 2 . 181–8 . February 1996 . 8595539 . 10.1016/S1081-1206(10)63420-5. etal.
  20. Corren J, Storms W, Bernstein J, Berger W, Nayak A, Sacks H . Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis . Clinical Therapeutics . 27 . 5 . 543–53 . May 2005 . 15978303 . 10.1016/j.clinthera.2005.04.012.
  21. Berger W, Hampel F, Bernstein J, Shah S, Sacks H, Meltzer EO . Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis . Annals of Allergy, Asthma & Immunology . 97 . 3 . 375–81 . September 2006 . 17042145 . 10.1016/S1081-1206(10)60804-6.
  22. Kalpaklioglu AF, Kavut AB . Comparison of azelastine versus triamcinolone nasal spray in allergic and nonallergic rhinitis . American Journal of Rhinology & Allergy . 24 . 1 . 29–33 . 2010 . 20109317 . 10.2500/ajra.2010.24.3423 . 24449860 .
  23. Bernstein JA . Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability . Current Medical Research and Opinion . 23 . 10 . 2441–52 . October 2007 . 17723160 . 10.1185/030079907X226302 . 25827650 .
  24. Horak F, Zieglmayer UP . Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis . Expert Review of Clinical Immunology . 5 . 6 . 659–669 . November 2009 . 20477689 . 10.1586/eci.09.38 . 32512061 .
  25. drugs.com Azelastine Page accessed 28 June 2015

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