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Identification
NameAzelastine
Accession NumberDB00972  (APRD00813)
TypeSmall Molecule
GroupsApproved
Description

Azelastine, a phthalazine derivative, is an antihistamine and mast cell stabilizer available as a nasal spray for hay fever and as eye drops for allergic conjunctivitis. Azelastine is also available as a combination product of azelastine hydrochloride and fluticasone propionate called Dymista™. Dymista™ is indicated in patient over 12 years old for symptomatic relief of seasonal allergic rhinitis.

Structure
Thumb
Synonyms
SynonymLanguageCode
4-(P-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinoneNot AvailableNot Available
AzelastinaSpanishINN
AzelastinumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Astelinspray, metered137 ugnasalMeda Pharmaceuticals Inc.1996-11-152016-11-30Us
Asteprospray, metered205.5 ugnasalMeda Pharmaceuticals Inc.2009-10-12Not AvailableUs
Optivarsolution/ drops.5 mg/mLintraocularMeda Pharmaceuticals Inc.2000-05-22Not AvailableUs
Azelastine Hydrochloridespray, metered137 ugnasalWallace Pharmaceuticals Inc.2010-07-01Not AvailableUs
Azelastine Hydrochloridesolution/ drops.5 mg/mLintraocularWallace Pharmaceuticals Inc.2010-10-01Not AvailableUs
Astelinspray, metered137 ugnasalPhysicians Total Care, Inc.2004-05-25Not AvailableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Azelastine Hydrochloridespray, metered137 ugnasalRoxane Laboratories, Inc.2014-10-27Not AvailableUs
Azelastine Hydrochloridespray, metered137 ugnasalSun Pharma Global FZE2012-05-24Not AvailableUs
Azelastine Hydrochloridesolution/ drops.5 mg/mLintraocularSun Pharma Global FZE2010-05-31Not AvailableUs
Azelastine Hydrochloridespray, metered137 ugnasalPhysicians Total Care, Inc.2011-06-28Not AvailableUs
Azelastine Hydrochloridesolution/ drops.5 mg/mLintraocularApotex Corp.2009-12-01Not AvailableUs
Azelastine Hydrochloridespray, metered137 ugnasalApotex Corp.2010-03-01Not AvailableUs
Azelastine Hydrochloridespray, metered205.5 ugnasalApotex Corp.2014-07-07Not AvailableUs
Azelastine Hydrochloridesolution/ drops.5 mg/mLintraocularSandoz Inc2013-03-21Not AvailableUs
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixtures
Brand NameIngredients
Dymistaazelastine hydrochloride and fluticasone propionate
Salts
Name/CASStructureProperties
Azelastine Hydrochloride
79307-93-0
Thumb
  • InChI Key: YEJAJYAHJQIWNU-UHFFFAOYNA-N
  • Monoisotopic Mass: 417.137467851
  • Average Mass: 418.359
DBSALT000013
Categories
CAS number58581-89-8
WeightAverage: 381.898
Monoisotopic: 381.160790112
Chemical FormulaC22H24ClN3O
InChI KeyMBUVEWMHONZEQD-UHFFFAOYSA-N
InChI
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
IUPAC Name
4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)-1,2-dihydrophthalazin-1-one
SMILES
CN1CCCC(CC1)N1N=C(CC2=CC=C(Cl)C=C2)C2=CC=CC=C2C1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phthalazinones. These are compounds containing a phthalazine bearing a ketone group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassPhthalazines
Direct ParentPhthalazinones
Alternative Parents
Substituents
  • Phthalazinone
  • Pyridazinone
  • Halobenzene
  • Chlorobenzene
  • Azepane
  • Benzenoid
  • Pyridazine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the symptomatic treatment of seasonal allergic rhinitis and non-allergic rhinitis, as well as symptomatic relief of ocular itching associated with allergic conjunctivitis.
PharmacodynamicsAzelastine is a relatively selective histamine H1 antagonist, which inhibits the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. It has some affinity to H2 receptors. Based on in vitro studies using human cell lines, inhibition of other mediators involved in allergic reactions (e.g. leukotrienes and PAF) has been demonstrated with azelastine. Azelastine may also inhibit the accumulation and degranulation of eosinophils at the site of allergic inflammation.
Mechanism of actionAzelastine competes with histamine for the H1-receptor sites on effector cells and acts as an antagonist by inhibiting the release of histamine and other mediators involved in the allergic response.
AbsorptionAbsorption of azelastine following ocular administration was relatively low. Systemic bioavailability is approximately 40% after nasal administration.
Volume of distribution
  • 14.5 L/kg
Protein bindingIn-vitro studies in human plasma indicate that the plasma protein binding of azelastine and N-desmethylazelastine are approximately 88% and 97%, respectively.
Metabolism

Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system, however the exact cytochrome P450 isoenzyme involved has not been determined. The major metabolite, desmethylazelastine, also has H1-receptor antagonist activity.

SubstrateEnzymesProduct
Azelastine
DesmethylazelastineDetails
Route of eliminationApproximately 75% of an oral dose of radiolabeled azelastine hydrochloride was excreted in the feces with less than 10% as unchanged azelastine. Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system.
Half lifeElimination half-life (based on intravenous and oral administration) is 22 hours. Elimination half-life of the active metabolite, desmethylazelastine, is 54 hours (after oral administration of azelastine).
Clearance
  • 0.5 L/h/kg [symptomatic patients]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.982
Caco-2 permeable-0.5102
P-glycoprotein substrateSubstrate0.7034
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.9563
Renal organic cation transporterInhibitor0.6812
CYP450 2C9 substrateNon-substrate0.7501
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.8204
CYP450 1A2 substrateInhibitor0.6371
CYP450 2C9 substrateNon-inhibitor0.8114
CYP450 2D6 substrateNon-inhibitor0.568
CYP450 2C19 substrateNon-inhibitor0.6934
CYP450 3A4 substrateNon-inhibitor0.5902
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7266
Ames testNon AMES toxic0.6567
CarcinogenicityNon-carcinogens0.878
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0597 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7885
hERG inhibition (predictor II)Inhibitor0.7391
Pharmacoeconomics
Manufacturers
  • Apotex inc richmond hill
  • Sun pharma global fze
  • Meda pharmaceuticals inc
  • Meda pharmaceuticals meda pharmaceuticals inc
  • Apotex inc
  • Meda pharmaceuticals
Packagers
Dosage forms
FormRouteStrength
Solution/ dropsintraocular.5 mg/mL
Spray, meterednasal137 ug
Spray, meterednasal205.5 ug
Prices
Unit descriptionCostUnit
Optivar 0.05% Solution 6ml Bottle120.26USD bottle
Astelin 137 mcg/spray Solution 30ml Bottle117.27USD bottle
Azelastine HCl 0.05% Solution 6ml Bottle108.23USD bottle
Optivar 0.05% drops19.27USD ml
Azelastine hcl 0.05% drops17.35USD ml
Astelin 137 mcg nasal spray3.71USD ml
Astepro 137 mcg nasal spray3.61USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States51641941994-05-012011-05-01
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point225 °C (hydrochloride salt)Not Available
water solubilitySparingly soluble (hydrochloride salt)Not Available
logP4.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0092 mg/mLALOGPS
logP3.81ALOGPS
logP4.04ChemAxon
logS-4.6ALOGPS
pKa (Strongest Basic)8.88ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area35.91 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity110.52 m3·mol-1ChemAxon
Polarizability41.54 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Yutaka Morita, Noritoshi Koyama, Shigemitsu Ohsawa, “Methods employing stable preparation containing azelastine hydrochloride.” U.S. Patent US6117864, issued December, 1990.

US6117864
General Reference
  1. Horak F: Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis. Ther Clin Risk Manag. 2008 Oct;4(5):1009-22. Pubmed
  2. Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. Pubmed
External Links
ATC CodesR01AC03R06AX19S01GX07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (17.5 KB)
MSDSDownload (36.8 KB)
Interactions
Drug Interactions
Drug
DihydrocodeineEnhanced CNS depressant effects contraindicates concurrent use.
gabapentin enacarbilAvoid combination due to increased CNS depression.
PerampanelAvoid combination with azelastine or other CNS depressants due to the combined increase of CNS depression.
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Azelastine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TrimethobenzamideTrimethobenzamide and Azelastine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineConcomitant therapy with triprolidine and azelastine, two anticholinergics and CNS depressants, may result in additive adverse/toxic effects. Monitor for enhanced anticholinergic and CNS depressant effects during concomitant therapy.
TrospiumTrospium and Azelastine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food InteractionsNot Available

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Casale TB: The interaction of azelastine with human lung histamine H1, beta, and muscarinic receptor-binding sites. J Allergy Clin Immunol. 1989 Apr;83(4):771-6. Pubmed
  2. Conde Hernandez DJ, Palma Aqilar JL, Delgado Romero J: Comparison of azelastine nasal spray and oral ebastine in treating seasonal allergic rhinitis. Curr Med Res Opin. 1995;13(6):299-304. Pubmed
  3. Antepara I, Jauregui I, Basomba A, Cadahia A, Feo F, Garcia JJ, Gonzalo MA, Luna I, Rubio M, Vazquez M: [Investigation of the efficacy and tolerability of azelastine nasal spray versus ebastine tablets in patients with seasonal allergic rhinitis] Allergol Immunopathol (Madr). 1998 Jan-Feb;26(1):9-16. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. Horak F: Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis. Ther Clin Risk Manag. 2008 Oct;4(5):1009-22. Pubmed
  6. Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. Pubmed
  7. Golden SJ, Craig TJ: Efficacy and safety of azelastine nasal spray for the treatment of allergic rhinitis. J Am Osteopath Assoc. 1999 Jul;99(7 Suppl):S7-12. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

6. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

7. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

9. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

10. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

11. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport. Eur J Pharm Sci. 2001 Feb;12(4):505-13. Pubmed
  2. Hu YP, Robert J: Azelastine and flezelastine as reversing agents of multidrug resistance: pharmacological and molecular studies. Biochem Pharmacol. 1995 Jul 17;50(2):169-75. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12