Azelastine

Azelastine, sold under the brand name Optivar 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.[4][5] Other uses may include asthma and skin rashes for which it is taken by mouth.[6] Onset of effects is within minutes when used in the eyes and within an hour when used in the nose.[7] Effects last for up to 12 hours.[7]

Azelastine
Clinical data
Trade namesAstelin, Optivar, Allergodil, others.[1]
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) [3]
Metabolitesdesmethylazelastine (active) [3]
Onset of actionWithin 1 hour [3]
Elimination half-life22 hours [3]
Duration of action12 hours [3]
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
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)

Common side effects include headache, sleepiness, change in taste, and sore throat.[7] It is unclear if use is safe during pregnancy or breastfeeding.[8] It is a second-generation antihistamine and works by blocking the release of a number of inflammatory mediators including histamine.[6][7]

Azelastine was patented in 1971 and came into medical use in 1986.[9] It is available as a generic medication[2] in the United States. In 2020, it was the 173rd most commonly prescribed medication in the United States, with more than 3 million 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.[14] 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).[7]

Pharmacology

Pharmacodynamics

Azelastine has a triple mode of action:[24]

  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.[3] Maximum plasma concentrations (Cmax) are observed within 2–3 hours.[3] 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

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]

References
  1. Drugs.com Drugs.com international listings for azelastine Page accessed June 28, 2015
  2. "FDA Approves a Nasal Antihistamine for Nonprescription Use". U.S. Food and Drug Administration (FDA) (Press release). 17 June 2021. Retrieved 21 June 2021.
  3. 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 ...
  4. British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 1169. ISBN 9780857113382.
  5. Al-Ahmad M, Hassab M, Al Ansari A (2020-12-21). "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. Intranasal H1 antihistamines such as azelastine are effective for controlling nasal symptoms. They need to be applied twice daily.
  6. Aronson JK (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 782. ISBN 9780444537164.
  7. "Azelastine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists.
  8. "Azelastine ophthalmic (Optivar) Use During Pregnancy". Drugs.com. Retrieved 26 March 2019.
  9. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN 9783527607495.
  10. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  11. "Azelastine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  12. AHRQ Allergic Rhinitis and its Impact on Asthma (ARIA) treatment guidelines Archived 2013-02-18 at the Wayback Machine
  13. "Rhinolast Nasal Spray Summary of Product Characteristics". Oct 2009. Retrieved 2010-04-27.
  14. "Astelin- azelastine hydrochloride spray, metered".
  15. "Optilast Eye Drops Summary of Product Characteristics". Jan 2010. Retrieved 2010-04-27.
  16. "Optivar- azelastine hydrochloride solution/ drops".
  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. 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 June 28, 2015
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