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{{Short description|Chemical compound}}
{{Drugbox
{{Use dmy dates|date=February 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| verifiedrevid = 458613328
| verifiedrevid = 458613328
| image = Azelastine.svg
| image = Azelastine.svg
| width = 150
| width = 150
| alt =
| caption =
| image2 = Azelastine-based-on-xtal-3D-bs-17.png
| image2 = Azelastine-based-on-xtal-3D-bs-17.png
| width2 = 200
| width2 = 200
| alt2 =


<!--Clinical data-->
<!-- Clinical data -->
| pronounce =
| tradename = Astelin, Optivar, Allergodil, others.<ref name=Names/>
| tradename = Astelin, others
| Drugs.com = {{drugs.com|monograph|azelastine}}
| Drugs.com = {{drugs.com|monograph|azelastine}}
| MedlinePlus = a603009
| MedlinePlus = a603009
| DailyMedID = Azelastine
| DailyMedID = Azelastine
| pregnancy_AU = B3
| pregnancy_AU = B3
| pregnancy_AU_comment =
| pregnancy_AU_comment =
| pregnancy_US = C
| pregnancy_US_comment =
| pregnancy_category=
| pregnancy_category=
| routes_of_administration = Eye drops, nasal spray, by mouth
| routes_of_administration = [[Ophthalmic drug administration|Eye drops]], [[Nasal administration|nasal spray]], [[Oral administration|by mouth]]
| class =
| ATC_prefix = R01
| ATC_prefix = R01
| ATC_suffix = AC03
| ATC_suffix = AC03
| ATC_supplemental = {{ATC|R06|AX19}}, {{ATC|S01|GX07}}
| ATC_supplemental = {{ATC|R06|AX19}}, {{ATC|S01|GX07}}


<!-- Legal status -->
| legal_AU = S2
| legal_AU = S2
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx Only
| legal_US = Rx Only
| legal_US_comment = /&nbsp;OTC<ref name="Astelin FDA label" /><ref name="Optivar FDA label" /><ref name="Astepro FDA PR" />
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!--Pharmacokinetic data-->
<!-- Pharmacokinetic data -->
| bioavailability = 40% (intranasal)
| bioavailability = 40% (intranasal) <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| protein_bound =
| elimination_half-life = 22 hours
| metabolism =
| metabolites = desmethylazelastine (active) <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| onset = Within 1 hour <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329">{{cite book | vauthors = Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ | title=Clinical Immunology | chapter=Antihistamines | publisher=Elsevier | year=2008 | doi=10.1016/b978-0-323-04404-2.10089-2 | pages=1317–1329 | isbn=9780323044042 | quote=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 ...}}</ref>
| elimination_half-life = 22 hours <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| duration_of_action = 12 hours <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| excretion =


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


<!--Chemical data-->
<!-- Chemical and physical data -->
| IUPAC_name = (''RS'')-4-[(4-Chlorophenyl)methyl]-2-(1-methylazepan-4-yl)-phthalazin-1-one
| IUPAC_name = (''RS'')-4-[(4-Chlorophenyl)methyl]-2-(1-methylazepan-4-yl)-phthalazin-1-one
| C=22 | H=24
| C=22 | H=24
| Cl=1 | N=3
| Cl=1 | N=3
| O=1
| O=1
| smiles = Clc1ccc(cc1)CC\3=N\N(C(=O)c2ccccc2/3)C4CCCN(C)CC4
| SMILES = Clc1ccc(cc1)CC\3=N\N(C(=O)c2ccccc2/3)C4CCCN(C)CC4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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 = 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_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MBUVEWMHONZEQD-UHFFFAOYSA-N
| StdInChIKey = MBUVEWMHONZEQD-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}


<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Azelastine''', sold under the brand name '''Optivar''' among others, is a 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=9780857113382|pages=1169|edition=76}}</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 |language=en}}</ref> Effects last for up to 12 hours.<ref name=AHFS2019/>
'''Azelastine''', sold under the brand name '''Astelin''' among others, is a [[H1 antagonist|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=9780857113382|pages=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/>


<!-- Side effects and mechanism -->
<!-- Side effects and mechanism -->
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 |language=en}}</ref> It is a second-generation [[antihistamine]] and works by blocking the release of a number of [[inflammation|inflammatory]] mediators including [[histamine]].<ref name=Aron2015>{{cite book |last1=Aronson |first1=Jeffrey K. |title=Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions |date=2015 |publisher=Elsevier |isbn=9780444537164 |page=782 |url=https://books.google.com/books?id=NOKoBAAAQBAJ&pg=PA782 |language=en}}</ref><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 [[inflammation|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=9780444537164 |page=782 |url=https://books.google.com/books?id=NOKoBAAAQBAJ&pg=PA782 }}</ref><ref name=AHFS2019/>


<!-- Society and culture -->
<!-- Society and culture -->
Azelastine was patented in 1971 and came into medical use in 1986.<ref name=Fis2006>{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=548 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA548 |language=en}}</ref> It is available as a [[generic medication]]. In 2017, it was the 297th most commonly prescribed medication in the United States, with more than one million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 11 April 2020}}</ref><ref>{{cite web | title = Azelastine Hydrochloride - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/AzelastineHydrochloride | access-date = 11 April 2020}}</ref>
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=9783527607495 |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 | 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 2022, it was the 124th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Azelastine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Azelastine | access-date = 30 August 2024 }}</ref>


==Medical uses==
==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>
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 adults and children 5 years of age and older.<ref name=AHRQ>AHRQ [http://www.guidelines.gov/content.aspx?id=24599 Allergic Rhinitis and its Impact on Asthma (ARIA) treatment guidelines] {{Webarchive|url=https://web.archive.org/web/20130218225136/http://www.guidelines.gov/content.aspx?id=24599 |date=2013-02-18 }}</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 = 2010-04-27
}}</ref><ref name="Astelin FDA Prescribing Information">
{{cite web
| url = https://www.drugs.com/pro/astelin.html| title = Astelin FDA Prescribing Information
| access-date = 2010-04-27
}}</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 Prescribing Information" /> 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 = 2010-04-27
}}</ref><ref name="Optivar Eye Drops FDA Prescribing Information">
{{cite web
| url = https://www.drugs.com/pro/optivar.html| title = Optivar Eye Drops FDA Prescribing Information| date = Jan 2010
| access-date = 2010-04-27
}}</ref>


==Side effects==
==Side effects==
Azelastine is safe and well tolerated in both adults and children with [[allergic rhinitis]].<ref>{{cite journal|last1=McNeely|first1=W|last2=Wiseman|first2=LR|title=Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis.|journal=Drugs|date=July 1998|volume=56|issue=1|pages=91–114|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.
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>Am J Rhinol Allergy 2010;24:29-33</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>Curr Med Res Opin 2007;23:2441-52</ref>
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).<ref name="AHFS2019" />
In addition, [[anosmia]] (loss in the ability to smell) can occur with nasal spray antihistamines (including both formulations of azelastine).<ref name="AHFS2019" />
Line 106: Line 140:


=== Pharmacokinetics ===
=== 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]], 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 are not affected by age, gender or hepatic impairment.<ref name="Horak & Zieglmayer, 2009" />
The systemic [[bioavailability]] of azelastine is approximately 40% when administered intranasally.<ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/> Maximum plasma concentrations (Cmax) are observed within 2–3 hours.<ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/> 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.<ref name="Horak & Zieglmayer, 2009" />


==== Metabolism ====
==== 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 |doi=10.1586/eci.09.38 |pmid=20477689 |title=Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis |year=2009 |last1=Horak |first1=Friedrich |last2=Zieglmayer |first2=Ursula Petra |journal=Expert Review of Clinical Immunology |volume=5 |issue=6 |pages=659–69|s2cid=32512061 }}</ref>
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==
==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 June 28, 2015</ref>
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>
{{-}}


==References==
==References==
{{Reflist}}
{{Reflist}}

==External links==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/azelastine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Azelastine }}
* [https://web.archive.org/web/20110728174711/http://www.whiar.org/Documents%26Resources.php#1 Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines]


{{Antihistamines}}
{{Antihistamines}}
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{{Leukotriene signaling modulators}}
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[[Category:Wikipedia medicine articles ready to translate]]
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[[Category:H1 receptor antagonists]]
[[Category:Azepanes]]
[[Category:Azepanes]]
[[Category:Chloroarenes]]
[[Category:4-Chlorophenyl compounds]]
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[[Category:H1 receptor antagonists]]
[[Category:Lactams]]
[[Category:Mast cell stabilizers]]
[[Category:Mast cell stabilizers]]
[[Category:Phthalazines]]
[[Category:Phthalazines]]
[[Category:Lactams]]
[[Category:Wikipedia medicine articles ready to translate]]

Latest revision as of 04:04, 30 September 2024

Azelastine
Clinical data
Trade namesAstelin, others
AHFS/Drugs.comMonograph
MedlinePlusa603009
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Eye drops, nasal spray, by mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability40% (intranasal) [4]
Metabolitesdesmethylazelastine (active) [4]
Onset of actionWithin 1 hour [4]
Elimination half-life22 hours [4]
Duration of action12 hours [4]
Identifiers
  • (RS)-4-[(4-Chlorophenyl)methyl]-2-(1-methylazepan-4-yl)-phthalazin-1-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.133.278 Edit this at Wikidata
Chemical and physical data
FormulaC22H24ClN3O
Molar mass381.90 g·mol−1
3D model (JSmol)
  • Clc1ccc(cc1)CC\3=N\N(C(=O)c2ccccc2/3)C4CCCN(C)CC4
  • InChI=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 checkY
  • Key:MBUVEWMHONZEQD-UHFFFAOYSA-N checkY
  (verify)

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.[5][6] Other uses may include asthma and skin rashes for which it is taken by mouth.[7] Onset of effects is within minutes when used in the eyes and within an hour when used in the nose.[8] Effects last for up to 12 hours.[8]

Common side effects include headache, sleepiness, change in taste, and sore throat.[8] It is unclear if use is safe during pregnancy or breastfeeding.[9] It is a second-generation antihistamine and works by blocking the release of a number of inflammatory mediators including histamine.[7][8]

Azelastine was patented in 1971 and came into medical use in 1986.[10] It is available as a generic medication.[3][11] In 2022, it was the 124th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[12][13]

Medical uses

[edit]

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.[14][15][1] In some countries, it is also indicated for the treatment of vasomotor rhinitis in adults and children ≥ 12 years old.[1] Azelastine eye drops are indicated for the local treatment of seasonal and perennial allergic conjunctivitis.[16][2]

Side effects

[edit]

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[needs update?]. 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).[8]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Azelastine has a triple mode of action:[24]

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

Pharmacokinetics

[edit]

The systemic bioavailability of azelastine is approximately 40% when administered intranasally.[4] Maximum plasma concentrations (Cmax) are observed within 2–3 hours.[4] 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.[24]

Metabolism

[edit]

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

Chemical properties

[edit]

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]

References

[edit]
  1. ^ a b c "Astelin- azelastine hydrochloride spray, metered".
  2. ^ a b "Optivar- azelastine hydrochloride solution/ drops".
  3. ^ a b "FDA Approves a Nasal Antihistamine for Nonprescription Use". U.S. Food and Drug Administration (FDA) (Press release). 17 June 2021. Retrieved 21 June 2021.
  4. ^ a b c d e f g Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ (2008). "Antihistamines". Clinical Immunology. Elsevier. pp. 1317–1329. doi:10.1016/b978-0-323-04404-2.10089-2. ISBN 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 ...
  5. ^ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 1169. ISBN 9780857113382.
  6. ^ Al-Ahmad M, Hassab M, Al Ansari A (21 December 2020). "Allergic and Non-allergic Rhinitis". Textbook of Clinical Otolaryngology. Cham: Springer International Publishing. pp. 241–252. doi:10.1007/978-3-030-54088-3_22. ISBN 978-3-030-54087-6. S2CID 234142758.
  7. ^ a b Aronson JK (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 782. ISBN 9780444537164.
  8. ^ a b c d e "Azelastine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists.
  9. ^ "Azelastine ophthalmic (Optivar) Use During Pregnancy". Drugs.com. Retrieved 26 March 2019.
  10. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN 9783527607495.
  11. ^ "First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 8 July 2024. Retrieved 9 July 2024.
  12. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  13. ^ "Azelastine Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  14. ^ Bousquet J, Schünemann HJ, Togias A, Bachert C, Erhola M, Hellings PW, et al. (January 2020). "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. doi:10.1016/j.jaci.2019.06.049. hdl:10400.17/3723. PMID 31627910.
  15. ^ "Rhinolast Nasal Spray Summary of Product Characteristics". October 2009. Retrieved 27 April 2010.
  16. ^ "Optilast Eye Drops Summary of Product Characteristics". January 2010. Retrieved 27 April 2010.
  17. ^ McNeely W, Wiseman LR (July 1998). "Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis". Drugs. 56 (1): 91–114. doi:10.2165/00003495-199856010-00011. PMID 9664202. S2CID 46956783.
  18. ^ Ratner PH, Findlay SR, Hampel F, van Bavel J, Widlitz MD, Freitag JJ (November 1994). "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. doi:10.1016/0091-6749(94)90148-1. PMID 7963150.
  19. ^ LaForce C, Dockhorn RJ, Prenner BM, et al. (February 1996). "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. doi:10.1016/S1081-1206(10)63420-5. PMID 8595539.
  20. ^ Corren J, Storms W, Bernstein J, Berger W, Nayak A, Sacks H (May 2005). "Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis". Clinical Therapeutics. 27 (5): 543–53. doi:10.1016/j.clinthera.2005.04.012. PMID 15978303.
  21. ^ Berger W, Hampel F, Bernstein J, Shah S, Sacks H, Meltzer EO (September 2006). "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. doi:10.1016/S1081-1206(10)60804-6. PMID 17042145.
  22. ^ Kalpaklioglu AF, Kavut AB (2010). "Comparison of azelastine versus triamcinolone nasal spray in allergic and nonallergic rhinitis". American Journal of Rhinology & Allergy. 24 (1): 29–33. doi:10.2500/ajra.2010.24.3423. PMID 20109317. S2CID 24449860.
  23. ^ Bernstein JA (October 2007). "Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability". Current Medical Research and Opinion. 23 (10): 2441–52. doi:10.1185/030079907X226302. PMID 17723160. S2CID 25827650.
  24. ^ a b c Horak F, Zieglmayer UP (November 2009). "Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis". Expert Review of Clinical Immunology. 5 (6): 659–669. doi:10.1586/eci.09.38. PMID 20477689. S2CID 32512061.
  25. ^ drugs.com Azelastine Page accessed 28 June 2015
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