Chemistry:Azelastine

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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.[1][2] Other uses may include asthma and skin rashes for which it is taken by mouth.[3] 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.[3][4]

Azelastine was patented in 1971 and came into medical use in 1986.[6] It is available as a generic medication.[7][8] In 2023, it was the 142nd most commonly prescribed medication in the United States, with more than 3 million prescriptions.[9][10]

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.[11][12][13] In some countries, it is also indicated for the treatment of vasomotor rhinitis in adults and children ≥ 12 years old.[13] Azelastine eye drops are indicated for the local treatment of seasonal and perennial allergic conjunctivitis.[14][15]

Side effects

Azelastine is safe and well tolerated in both adults and children with allergic rhinitis.[16][17][18] 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[19][20] 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.[21] 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.[22]

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:[23]

  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. 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.[23]

Metabolism

Azelastine is oxidatively metabolized by the cytochrome P450 family into its active metabolite, desmethylazelastine, and two inactive carboxylic acid metabolites.[23]

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.[24]

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.[25]

An ophthalmic drop formulation of azelastine (Optivar) was approved by the US FDA in 2000.[26] Prescription nasal spray formulations were approved in 1996 (Astelin) and 2008 (Astepro),[27] with Astepro becoming available over‑the‑counter in 2021.[28]

Research

Azelastine may have in vitro antiviral activity against respiratory viruses, including SARS-CoV-2.[29][30][31] 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.[29] 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.[32]

References

  1. ↑ British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 1169. ISBN 978-0-85711-338-2. 
  2. ↑ "Allergic and Non-allergic Rhinitis". Textbook of Clinical Otolaryngology. Cham: Springer International Publishing. 21 December 2020. pp. 241–252. doi:10.1007/978-3-030-54088-3_22. ISBN 978-3-030-54087-6. 
  3. ↑ 3.0 3.1 Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. 2015. p. 782. ISBN 978-0-444-53716-4. https://books.google.com/books?id=NOKoBAAAQBAJ&pg=PA782. 
  4. ↑ 4.0 4.1 4.2 4.3 "Azelastine Hydrochloride Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/azelastine-hydrochloride.html. 
  5. ↑ "Azelastine ophthalmic (Optivar) Use During Pregnancy". https://www.drugs.com/pregnancy/azelastine-ophthalmic.html. 
  6. ↑ Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 548. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA548. 
  7. ↑ "FDA Approves a Nasal Antihistamine for Nonprescription Use". U.S. Food and Drug Administration (FDA) (Press release). 17 June 2021. Archived from the original on 17 June 2021. Retrieved 21 June 2021.
  8. ↑ "First Generic Drug Approvals". 8 July 2024. https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals. 
  9. ↑ "Top 300 of 2023". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  10. ↑ "Azelastine Drug Usage Statistics, United States, 2013 - 2023". https://clincalc.com/DrugStats/Drugs/Azelastine. 
  11. ↑ "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. doi:10.1016/j.jaci.2019.06.049. PMID 31627910. 
  12. ↑ "Rhinolast Nasal Spray Summary of Product Characteristics". Oct 2009. http://www.medicines.org.uk/EMC/medicine/9160/SPC/Rhinolast+Nasal+Spray/. 
  13. ↑ 13.0 13.1 "Astelin- azelastine hydrochloride spray, metered". https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=520663. 
  14. ↑ "Optilast Eye Drops Summary of Product Characteristics". Jan 2010. http://www.medicines.org.uk/EMC/medicine/9161/SPC/Optilast+Eye+Drops/. 
  15. ↑ "Optivar- azelastine hydrochloride solution/ drops". https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=281009. 
  16. ↑ "Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis". Drugs 56 (1): 91–114. July 1998. doi:10.2165/00003495-199856010-00011. PMID 9664202. 
  17. ↑ "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. doi:10.1016/0091-6749(94)90148-1. PMID 7963150. 
  18. ↑ "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. doi:10.1016/S1081-1206(10)63420-5. PMID 8595539. 
  19. ↑ "Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis". Clinical Therapeutics 27 (5): 543–53. May 2005. doi:10.1016/j.clinthera.2005.04.012. PMID 15978303. 
  20. ↑ "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. doi:10.1016/S1081-1206(10)60804-6. PMID 17042145. 
  21. ↑ "Comparison of azelastine versus triamcinolone nasal spray in allergic and nonallergic rhinitis". American Journal of Rhinology & Allergy 24 (1): 29–33. 2010. doi:10.2500/ajra.2010.24.3423. PMID 20109317. 
  22. ↑ "Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability". Current Medical Research and Opinion 23 (10): 2441–52. October 2007. doi:10.1185/030079907X226302. PMID 17723160. 
  23. ↑ 23.0 23.1 23.2 "Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis". Expert Review of Clinical Immunology 5 (6): 659–669. November 2009. doi:10.1586/eci.09.38. PMID 20477689. 
  24. ↑ drugs.com Azelastine Page accessed 28 June 2015
  25. ↑ "E-0659 (Azelastine)に よ る慢 性蕁 麻 疹 の 治 療 経 験" (in ja). Skin Research 31 (3): 472–476. 1989. doi:10.11340/skinresearch1959.31.472. https://www.jstage.jst.go.jp/article/skinresearch1959/31/3/31_3_472/_article/-char/en. Retrieved 29 July 2025. 
  26. ↑ "Evaluation of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen challenge model". Clinical Therapeutics 23 (8): 1272–80. August 2001. doi:10.1016/s0149-2918(01)80106-5. PMID 11558863. 
  27. ↑ "The efficacy of intranasal antihistamines in the treatment of allergic rhinitis". Annals of Allergy, Asthma & Immunology 106 (2 Suppl): S6–S11. February 2011. doi:10.1016/j.anai.2010.08.010. PMID 21277531. 
  28. ↑ Park, Brian (June 18, 2021). "FDA Approves Rx-to-OTC Switch for Astepro Allergy Nasal Spray". https://www.empr.com/home/news/fda-approves-rx-to-otc-switch-for-astepro-allergy-nasal-spray/. 
  29. ↑ 29.0 29.1 "Potential Protective Factors for Allergic Rhinitis Patients Infected with COVID-19". Current Issues in Molecular Biology 46 (7): 6633–6645. June 2024. doi:10.3390/cimb46070395. PMID 39057037. 
  30. ↑ "Effectiveness of antihistamines in COVID-19 symptoms: a systematic review study". Jundishapur Journal of Sciences: 800–810. 3 February 2024. doi:10.32592/JSMJ.22.6.800. https://jsmj.ajums.ac.ir/article_189630_a205e0a5dee552d244da83c8c36d08a4.pdf. Retrieved 7 October 2025. 
  31. ↑ "Current status of antihistamine drugs repurposing for infectious diseases". Medicine in Drug Discovery 15. 2022. doi:10.1016/j.medidd.2022.100140. 
  32. ↑ "Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial". JAMA Internal Medicine. September 2025. doi:10.1001/jamainternmed.2025.4283. PMID 40892398. 



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