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Identification
Name Fexofenadine
Accession Number DB00950 (APRD00349)
Type small molecule
Groups approved
Description

Fexofenadine hydrochloride (Allegra) is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. It was developed as a successor of and alternative to terfenadine. Fexofenadine, like other second and third-generation antihistamines, does not readily pass through the blood-brain barrier, and so causes less drowsiness than first-generation histamine-receptor antagonists.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Carboxyterfenadine
  • Fexofenadine hydrochloride
  • Fexofendine
  • Terfenadine acid metabolite
  • Terfenadine carboxylate
  • Terfenadine-COOH
Brand names
  • Allegra
  • Allegra-D 12 Hour
  • Allegra-D 24 Hour
Brand name mixtures
  • Allegra-D (Fexofenadine hydrochloride + Pseudoephedrine hydrochloride)
Categories
  • Anti-Allergic Agents
  • Antihistamines
  • Histamine H1 Antagonists, Non-Sedating
CAS number 83799-24-0
Weight Average: 501.6564
Monoisotopic: 501.287908741
Chemical Formula C32H39NO4
InChI Key InChIKey=RWTNPBWLLIMQHL-UHFFFAOYSA-N
InChI
InChI=1S/C32H39NO4/c1-31(2,30(35)36)25-17-15-24(16-18-25)29(34)14-9-21-33-22-19-28(20-23-33)32(37,26-10-5-3-6-11-26)27-12-7-4-8-13-27/h3-8,10-13,15-18,28-29,34,37H,9,14,19-23H2,1-2H3,(H,35,36)
Plain Text
IUPAC Name
2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanoic acid
SMILES
CC(C)(C(O)=O)C1=CC=C(C=C1)C(O)CCCN1CCC(CC1)C(O)(C1=CC=CC=C1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Diphenylmethanes
Substructures
  • Carbonyl Compounds
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Carboxylic Acids and Derivatives
  • Phenylacetates
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Diphenylmethanes
  • Heterocyclic compounds
  • Aromatic compounds
  • Piperidines
Pharmacology
Indication For management of Seasonal allergic rhinitis
Pharmacodynamics Fexofenadine is a second-generation, long lasting H1-receptor antagonist (antihistamine) which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergy. Fexofenadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Fexofenadine does not enter the brain from the blood and, therefore, does not cause drowsiness. Fexofenadine lacks the cardiotoxic potential of terfenadine, since it does not block the potassium channel involved in repolarization of cardiac cells.
Mechanism of action Like other H1-blockers, Fexofenadine competes with free histamine for binding at H1-receptors in the GI tract, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine. Fexofenadine exhibits no anticholinergic, antidopaminergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects.
Absorption 33%
Volume of distribution Not Available
Protein binding 60%-70%
Metabolism

Approximately 5% of the total dose is metabolized, by cytochrome P450 3A4 and by intestinal microflora.
Route of elimination Not Available
Half life 14.4 hours
Clearance Not Available
Toxicity Side effects include dizziness, drowsiness, and dry mouth.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Barr laboratories inc
  • Dr reddys laboratories ltd
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Sanofi-Aventis
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Allegra ODT 60 30 mg Dispersible Tablet Box 126.0 USD box
Allegra-D 24 Hour 180-240 mg 24 Hour tablet 5.01 USD tablet
Allegra-d 24 hour tablet 4.98 USD tablet
Allegra 180 mg tablet 2.89 USD tablet
Allegra-D 12 Hour 60-120 mg 12 Hour tablet 2.72 USD tablet
Allegra-d 12 hour tablet 2.49 USD tablet
Fexofenadine hcl 180 mg tablet 2.47 USD tablet
Allegra odt 30 mg tablet 1.98 USD tablet
Allegra 60 mg tablet 1.64 USD tablet
Fexofenadine hcl 60 mg tablet 1.43 USD tablet
Allegra 30 mg tablet 0.81 USD tablet
Fexofenadine hcl 30 mg tablet 0.71 USD tablet
Allegra 30 mg/5ml Suspension 0.25 USD ml
Patents
Country Patent Number Approved Expires
United States 6037353 1997-09-14 2017-09-14
United States 5178878 1993-01-12 2010-01-12
Canada 2301267 2004-07-13 2018-07-21
Canada 2134211 1999-06-29 2013-04-06
Properties
State solid
Melting point 142.5 oC
Experimental Properties
Property Value Source
water solubility Slightly soluble PhysProp
logP 5.6 PhysProp
Predicted Properties
Property Value Source
water solubility 2.66e-03 g/l ALOGPS
logP 5.02 ALOGPS
logP 0.85 ChemAxon Molconvert
logS -5.28 ALOGPS
pKa 13.20 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 81.00 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 147.98 ChemAxon Molconvert
polarizability 57.42 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Smith SM, Gums JG: Fexofenadine: biochemical, pharmacokinetic and pharmacodynamic properties and its unique role in allergic disorders. Expert Opin Drug Metab Toxicol. 2009 Jul;5(7):813-22. Pubmed
  2. Bachert C: A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis. Clin Ther. 2009 May;31(5):921-44. Pubmed
  3. Markham A, Wagstaff AJ: Fexofenadine. Drugs. 1998 Feb;55(2):269-74; discussion 275-6. Pubmed
  4. Golightly LK, Greos LS: Second-generation antihistamines: actions and efficacy in the management of allergic disorders. Drugs. 2005;65(3):341-84. Pubmed
  5. Molimard M, Diquet B, Benedetti MS: Comparison of pharmacokinetics and metabolism of desloratadine, fexofenadine, levocetirizine and mizolastine in humans. Fundam Clin Pharmacol. 2004 Aug;18(4):399-411. Pubmed
External Links
Resource Link
KEGG Compound C06999 Link_out
PubChem Compound 3348 Link_out
PubChem Substance 46504676 Link_out
ChemSpider 3231 Link_out
BindingDB 22874 Link_out
ChEBI 5050 Link_out
ChEMBL 5050 Link_out
Therapeutic Targets Database DAP000330 Link_out
PharmGKB PA449621 Link_out
Drug Product Database 2242819 Link_out
RxList http://www.rxlist.com/cgi/generic/fexofen.htm Link_out
Drugs.com http://www.drugs.com/cdi/fexofenadine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Fexofenadine Link_out
ATC Codes
  • R06AX26
AHFS Codes
  • 04:08.00
PDB Entries Not Available
FDA label show (43.7 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Grapefruit and grapefruit juice should be avoided throughout treatment as grapefruit can significantly decrease serum levels of this product.
  • Take without regard to meals.
Targets

1. Histamine H1 receptor

Pharmacological action: yes
Actions: antagonist

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Amon U, Amon S, Gibbs BF: In vitro studies with fexofenadine, a new nonsedating histamine H1 receptor antagonist, on isolated human basophils. Inflamm Res. 2000 Apr;49 Suppl 1:S13-4. Pubmed
  3. Abbas MN, Abdel Fattah AA, Zahran E: A novel membrane sensor for histamine H1-receptor antagonist “fexofenadine”. Anal Sci. 2004 Aug;20(8):1137-42. Pubmed
  4. Grzelewska-Rzymowska I, Kroczynska-Bednarek J, Pietrzkowicz M: [Effect of fexofenadine—selective antagonist of histamine receptor (H1) on histamine-induced bronchoconstriction] Pol Merkur Lekarski. 2003 Jan;14(79):43-6. Pubmed
  5. Tashiro M, Sakurada Y, Iwabuchi K, Mochizuki H, Kato M, Aoki M, Funaki Y, Itoh M, Iwata R, Wong DF, Yanai K: Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol. 2004 Aug;44(8):890-900. Pubmed
  6. Cavero I, Mestre M, Guillon JM, Heuillet E, Roach AG: Preclinical in vitro cardiac electrophysiology: a method of predicting arrhythmogenic potential of antihistamines in humans? Drug Saf. 1999;21 Suppl 1:19-31; discussion 81-7. Pubmed
  7. Devillier P, Roche N, Faisy C: Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. Pubmed
  8. Dhanya NB, Thasleem Z, Rai R, Srinivas CR: Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test. Indian J Dermatol Venereol Leprol. 2008 Jul-Aug;74(4):361-3. Pubmed
  9. Smith SM, Gums JG: Fexofenadine: biochemical, pharmacokinetic and pharmacodynamic properties and its unique role in allergic disorders. Expert Opin Drug Metab Toxicol. 2009 Jul;5(7):813-22. Pubmed
  10. Markham A, Wagstaff AJ: Fexofenadine. Drugs. 1998 Feb;55(2):269-74; discussion 275-6. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. Pubmed
  2. Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA, Benet LZ: Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res. 1999 Apr;16(4):478-85. Pubmed
  3. Petri N, Tannergren C, Rungstad D, Lennernas H: Transport characteristics of fexofenadine in the Caco-2 cell model. Pharm Res. 2004 Aug;21(8):1398-404. Pubmed

2. Solute carrier organic anion transporter family member 2B1

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost

UniProt ID: O94956 Link_out
Gene: SLCO2B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I: Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45. Epub 2003 Nov 10. Pubmed

3. Solute carrier organic anion transporter family member 1A2

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on August 18, 2011 10:03

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.