Azelastine

{{Short description|Chemical compound}} {{Use dmy dates|date=September 2025}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | verifiedrevid = 458613328 | image = Azelastine.svg | image_class = skin-invert-image | width = 150 | alt = | caption = | image2 = Azelastine-based-on-xtal-3D-bs-17.png | image_class2 = bg-transparent | width2 = 200 | alt2 =

| pronounce = | tradename = Astelin, others | Drugs.com = {{drugs.com|monograph|azelastine}} | MedlinePlus = a603009 | DailyMedID = Azelastine | pregnancy_AU = B3 | pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = Eye drops, nasal spray, by mouth | class = | ATC_prefix = R01 | ATC_suffix = AC03 | ATC_supplemental = {{ATC|R06|AX19}}, {{ATC|S01|GX07}}

| legal_AU = S4 | legal_AU_comment = /{{nbsp}}Schedule 2<ref>{{cite web | title=Therapeutic Goods (Poisons Standard— June 2025) Instrument 2025 | website=Therapeutic Goods Administration (TGA) | date=May 2025 | url=https://www.legislation.gov.au/F2025L00599/asmade/2025-05-28/text/original/pdf | format=pdf | access-date=31 August 2025}}</ref> | legal_BR =  | legal_BR_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx Only | legal_US_comment = / OTC<ref name="Astelin FDA label" /><ref name="Optivar FDA label" /><ref name="Astepro FDA PR" /> | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| index2_label = as HCl | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 58581-89-8 | CAS_number2 = 79307-93-0 | CAS_supplemental = | PubChem = 2267 | PubChem2 = 54360 | IUPHAR_ligand = 7121 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00972 | DrugBank2 = DBSALT000013 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2180 | ChemSpiderID2 = 49103 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = ZQI909440X | UNII2 = 0L591QR10I | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07483 | KEGG2 = D00659 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 2950 | ChEBI2 = 2951 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 639 | ChEMBL2 = 1200809 | NIAID_ChemDB = | PDB_ligand = | synonyms =

| 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_Ref = {{stdinchicite|correct|chemspider}} | 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 | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = MBUVEWMHONZEQD-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Azelastine''', sold under the brand name '''Astelin''' among others, is a H<sub>1</sub> receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis.<ref name=BNF76>{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|page=1169|edition=76}}</ref><ref name="Al-Ahmad Hassab Al Ansari 2020 pp. 241–252">{{cite book | vauthors = Al-Ahmad M, Hassab M, Al Ansari A | title=Textbook of Clinical Otolaryngology | chapter=Allergic and Non-allergic Rhinitis | publisher=Springer International Publishing | publication-place=Cham | date=21 December 2020 | isbn=978-3-030-54087-6 | doi=10.1007/978-3-030-54088-3_22 | pages=241–252 | s2cid=234142758 }}</ref> Other uses may include asthma and skin rashes for which it is taken by mouth.<ref name=Aron2015/> Onset of effects is within minutes when used in the eyes and within an hour when used in the nose.<ref name=AHFS2019>{{cite web |title=Azelastine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/azelastine-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists }}</ref> Effects last for up to 12 hours.<ref name=AHFS2019/>

Common side effects include headache, sleepiness, change in taste, and sore throat.<ref name=AHFS2019/> It is unclear if use is safe during pregnancy or breastfeeding.<ref>{{cite web |title=Azelastine ophthalmic (Optivar) Use During Pregnancy |url=https://www.drugs.com/pregnancy/azelastine-ophthalmic.html |website=Drugs.com |access-date=26 March 2019 }}</ref> It is a second-generation antihistamine and works by blocking the release of a number of inflammatory mediators including histamine.<ref name=Aron2015>{{cite book | vauthors = Aronson JK |title=Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions |date=2015 |publisher=Elsevier |isbn=978-0-444-53716-4 |page=782 |url=https://books.google.com/books?id=NOKoBAAAQBAJ&pg=PA782 }}</ref><ref name=AHFS2019/>

Azelastine was patented in 1971 and came into medical use in 1986.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=548 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA548 }}</ref> It is available as a generic medication.<ref name="Astepro FDA PR">{{cite press release | title=FDA Approves a Nasal Antihistamine for Nonprescription Use | website=U.S. Food and Drug Administration (FDA) | date=17 June 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-nasal-antihistamine-nonprescription-use | archive-url=https://web.archive.org/web/20210617204917/https://www.fda.gov/news-events/press-announcements/fda-approves-nasal-antihistamine-nonprescription-use | archive-date=17 June 2021 | access-date=21 June 2021}}</ref><ref>{{cite web | title=First Generic Drug Approvals | website=U.S. Food and Drug Administration (FDA) | date=8 July 2024 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | access-date=9 July 2024}}</ref> In 2023, it was the 142nd most commonly prescribed medication in the United States, with more than 3{{nbsp}}million prescriptions.<ref name="Top 300">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Azelastine Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Azelastine | access-date = 18 August 2025 }}</ref>

==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.<ref>{{cite journal | vauthors = 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 | title = 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 | journal = The Journal of Allergy and Clinical Immunology | volume = 145 | issue = 1 | pages = 70–80.e3 | date = January 2020 | pmid = 31627910 | doi = 10.1016/j.jaci.2019.06.049 | hdl = 10400.17/3723 | hdl-access = free }}</ref><ref name="Rhinolast Nasal Spray">{{cite web | url = http://www.medicines.org.uk/EMC/medicine/9160/SPC/Rhinolast+Nasal+Spray/ | title = Rhinolast Nasal Spray Summary of Product Characteristics | date = Oct 2009 | access-date = 27 April 2010 }}</ref><ref name="Astelin FDA label">{{cite web | url = https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=520663 | title = Astelin- azelastine hydrochloride spray, metered }}</ref> In some countries, it is also indicated for the treatment of vasomotor rhinitis in adults and children ≥ 12 years old.<ref name="Astelin FDA label" /> Azelastine eye drops are indicated for the local treatment of seasonal and perennial allergic conjunctivitis.<ref name="Optilast Eye Drops Summary of Product Characteristics">{{cite web | url = http://www.medicines.org.uk/EMC/medicine/9161/SPC/Optilast+Eye+Drops/| title = Optilast Eye Drops Summary of Product Characteristics | date = Jan 2010 | access-date = 27 April 2010 }}</ref><ref name="Optivar FDA label">{{cite web | url = https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=281009| title = Optivar- azelastine hydrochloride solution/ drops }}</ref>

==Side effects== Azelastine is safe and well tolerated in both adults and children with allergic rhinitis.<ref>{{cite journal | vauthors = McNeely W, Wiseman LR | title = Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis | journal = Drugs | volume = 56 | issue = 1 | pages = 91–114 | date = July 1998 | pmid = 9664202 | doi = 10.2165/00003495-199856010-00011 | s2cid = 46956783 }}</ref><ref name="Ratner et al, 1994">{{cite journal |vauthors=Ratner PH, Findlay SR, Hampel F, van Bavel J, Widlitz MD, Freitag JJ |title=A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis |journal=The Journal of Allergy and Clinical Immunology |volume=94 |issue=5 |pages=818–25 |date=November 1994 |pmid=7963150 |doi=10.1016/0091-6749(94)90148-1}}</ref><ref name="LaForce et al, 1996">{{cite journal |vauthors=LaForce C, Dockhorn RJ, Prenner BM |title=Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial |journal=Annals of Allergy, Asthma & Immunology |volume=76 |issue=2 |pages=181–8 |date=February 1996 |pmid=8595539 |doi=10.1016/S1081-1206(10)63420-5|display-authors=etal}}</ref> 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{{update inline|reason=Does this still hold after so many years?|?=no|date=November 2017}}. More recent studies<ref name="Corren et al, 2005">{{cite journal |vauthors=Corren J, Storms W, Bernstein J, Berger W, Nayak A, Sacks H |title=Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis |journal=Clinical Therapeutics |volume=27 |issue=5 |pages=543–53 |date=May 2005 |pmid=15978303 |doi=10.1016/j.clinthera.2005.04.012}}</ref><ref name="Berger et al, 2006">{{cite journal |vauthors=Berger W, Hampel F, Bernstein J, Shah S, Sacks H, Meltzer EO |title=Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis |journal=Annals of Allergy, Asthma & Immunology |volume=97 |issue=3 |pages=375–81 |date=September 2006 |pmid=17042145 |doi=10.1016/S1081-1206(10)60804-6}}</ref> 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.<ref name="pmid20109317">{{cite journal | vauthors = Kalpaklioglu AF, Kavut AB | title = Comparison of azelastine versus triamcinolone nasal spray in allergic and nonallergic rhinitis | journal = American Journal of Rhinology & Allergy | volume = 24 | issue = 1 | pages = 29–33 | date = 2010 | pmid = 20109317 | doi = 10.2500/ajra.2010.24.3423 | s2cid = 24449860 }}</ref> 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.<ref name="pmid17723160">{{cite journal | vauthors = Bernstein JA | title = Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability | journal = Current Medical Research and Opinion | volume = 23 | issue = 10 | pages = 2441–52 | date = October 2007 | pmid = 17723160 | doi = 10.1185/030079907X226302 | s2cid = 25827650 }}</ref>

In addition, anosmia (loss in the ability to smell) can occur with nasal spray antihistamines (including both formulations of azelastine).{{medical citation needed|date=October 2025}}

==Pharmacology==

=== Pharmacodynamics === Azelastine has a triple mode of action:<ref name="Horak & Zieglmayer, 2009" /> # Anti-histamine effect, # Mast-cell stabilizing effect and # Anti-inflammatory effect.

=== Pharmacokinetics === The systemic bioavailability of azelastine is approximately 40% when administered intranasally. Maximum plasma concentrations (Cmax) are observed within 2–3 hours. The elimination half life is 22 h, the steady-state volume of distribution is 14.5 L/kg, and the plasma clearance is 0.5 L/h/kg (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.<ref name="Horak & Zieglmayer, 2009" />

==== Metabolism ==== Azelastine is oxidatively metabolized by the cytochrome P450 family into its active metabolite, desmethylazelastine, and two inactive carboxylic acid metabolites.<ref name="Horak & Zieglmayer, 2009">{{cite journal | vauthors = Horak F, Zieglmayer UP | title = Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis | journal = Expert Review of Clinical Immunology | volume = 5 | issue = 6 | pages = 659–669 | date = November 2009 | pmid = 20477689 | doi = 10.1586/eci.09.38 | s2cid = 32512061 }}</ref>

==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.<ref>drugs.com [https://www.drugs.com/pro/azelastine.html Azelastine] Page accessed 28 June 2015</ref>

== History == Azelastine was first synthesized by Dietrich in 1971, developed through collaborative research between Eisai Co., Ltd. in Japan and Degussa GmbH in West Germany.<ref>{{cite journal | vauthors = Mitsuhashi Y, Hashimoto I | title = E-0659 (Azelastine)による慢性蕁麻疹の治療経験 | journal = Skin Research | volume = 31 | issue = 3 | pages = 472–476 | date = 1989 | doi = 10.11340/skinresearch1959.31.472 | language = ja | trans-title = Treatment of chronic urticaria with E-0659 (Azelastine) | url = https://www.jstage.jst.go.jp/article/skinresearch1959/31/3/31_3_472/_article/-char/en | access-date = 29 July 2025 }}</ref>

An ophthalmic drop formulation of azelastine (Optivar) was approved by the US FDA in 2000.<ref name="pmid11558863">{{cite journal |vauthors=Spangler DL, Bensch G, Berdy GJ |title=Evaluation of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen challenge model |journal=Clinical Therapeutics |volume=23 |issue=8 |pages=1272–80 |date=August 2001 |pmid=11558863 |doi=10.1016/s0149-2918(01)80106-5}}</ref> Prescription nasal spray formulations were approved in 1996 (Astelin) and 2008 (Astepro),<ref name="pmid21277531">{{cite journal |vauthors=Kaliner MA, Berger WE, Ratner PH, Siegel CJ |title=The efficacy of intranasal antihistamines in the treatment of allergic rhinitis |journal=Annals of Allergy, Asthma & Immunology |volume=106 |issue=2 Suppl |pages=S6–S11 |date=February 2011 |pmid=21277531 |doi=10.1016/j.anai.2010.08.010}}</ref> with Astepro becoming available over‑the‑counter in 2021.<ref name="Park 2021">{{cite web |last=Park |first=Brian |title=FDA Approves Rx-to-OTC Switch for Astepro Allergy Nasal Spray |website=MPR |date=June 18, 2021 |url=https://www.empr.com/home/news/fda-approves-rx-to-otc-switch-for-astepro-allergy-nasal-spray/ |access-date=October 1, 2025}}</ref>

== Research == Azelastine may have in vitro antiviral activity against respiratory viruses, including SARS-CoV-2.<ref name="pmid39057037">{{cite journal |vauthors=Dong J, Su D, Zhao B, Han J, Tu M, Zhang K, Wang F, An Y |title=Potential Protective Factors for Allergic Rhinitis Patients Infected with COVID-19 |journal=Current Issues in Molecular Biology |volume=46 |issue=7 |pages=6633–6645 |date=June 2024 |pmid=39057037 |pmc=11275266 |doi=10.3390/cimb46070395 |doi-access=free }}</ref><ref name="Moomen 2024">{{cite journal |vauthors=Moomen T, Tavahen N, Asadsamani S |title=Effectiveness of antihistamines in COVID-19 symptoms: a systematic review study |journal=Jundishapur Journal of Sciences |date=3 February 2024 |doi=10.32592/JSMJ.22.6.800 |doi-access=free |pages=800–810 |url=https://jsmj.ajums.ac.ir/article_189630_a205e0a5dee552d244da83c8c36d08a4.pdf |access-date=7 October 2025}}</ref><ref name="Travi 2022">{{cite journal |vauthors=Travi BL |title=Current status of antihistamine drugs repurposing for infectious diseases |journal=Medicine in Drug Discovery |volume=15 |date=2022 |doi=10.1016/j.medidd.2022.100140 |doi-access=free |article-number=100140}}</ref> It is thought to work by interfering with the interaction of the SARS-CoV-2 spike glycoprotein and ACE2 by fixing the receptor in a closed form.<ref name="pmid39057037"/> In 2025, a small single-center phase II randomized trial found reduced incidence of PCR-confirmed SARS-CoV-2 infection, increased mean time to infection, and reduced PCR-confirmed rhinovirus infections by two thirds, without adverse effects.<ref name="pmid40892398">{{cite journal |vauthors=Lehr T, Meiser P, Selzer D, Rixecker T, Holzer F, Mösges R, Smola S, Bals R |title=Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial |journal=JAMA Internal Medicine |volume= |issue= |pages= |date=September 2025 |pmid=40892398 |doi=10.1001/jamainternmed.2025.4283 |pmc=12406145 }}</ref><ref name="Ricke 2026">{{cite journal |vauthors=Ricke DO |title=Mast cells and histamine receptor-targeted adjunctive treatments for COVID-19: A literature review |journal=Innovative Medicines & Omics |date=February 4, 2026 |issn=3060-8910 |doi=10.36922/IMO025440058 |article-number=025440058 |url=https://accscience.com/journal/IMO/articles/online_first/6199 |access-date=April 10, 2026}}</ref>

==References== {{Reflist}}

{{Antihistamines}} {{Histamine receptor modulators}} {{Leukotriene signaling modulators}} {{Portal bar | Medicine}} {{Authority control}}

Category:Azepanes Category:4-Chlorophenyl compounds Category:H1 receptor antagonists Category:Lactams Category:Mast cell stabilizers Category:Over-the-counter drugs in the United States Category:Phthalazines Category:Wikipedia medicine articles ready to translate