Misplaced Pages

Fexofenadine: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively
Page 1
Page 2
← Previous editContent deleted Content addedVisualWikitext
Revision as of 06:35, 8 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'StdInChI').← Previous edit Latest revision as of 23:50, 10 December 2024 edit undo2601:642:c303:f370:103a:b9cd:8e09:9e6 (talk) ce 
(358 intermediate revisions by more than 100 users not shown)
Line 1: Line 1:
{{Short description|Antihistamine medication}}
{{Drugbox
{{Use dmy dates|date=February 2022}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed | Watchedfields = changed
| verifiedrevid = 412105756 | verifiedrevid = 459589155
| image = Fexofenadine2DCSD.svg
| IUPAC_name = (''RS'')- 2-butyl]phenyl]- 2-methyl- propanoic acid
| alt = Skeletal formula of fexofenadine
| image = Fexofenadine.svg
| width = 200px | width = 260
| imagename = 1 : 1 mixture (racemate) | chirality = ]
| drug_name = Fexofenadine | image2 = Fexofenadine 3D ball.png
| alt2 = Ball-and-stick model of fexofenadine
| width2 =


<!--Clinical data--> <!-- Clinical data -->
| tradename = Allegra | pronounce =
| tradename = Allegra, others
| Drugs.com = {{drugs.com|monograph|fexofenadine-hydrochloride}} | Drugs.com = {{drugs.com|monograph|fexofenadine-hydrochloride}}
| MedlinePlus = a697035 | MedlinePlus = a697035
| licence_US = Fexofenadine | DailyMedID = Fexofenadine
| pregnancy_AU = B2 | pregnancy_AU = B2
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Fexofenadine Use During Pregnancy | website=Drugs.com | date=1 April 2019 | url=https://www.drugs.com/pregnancy/fexofenadine.html | access-date=26 July 2020}}</ref>
| pregnancy_US = C
| pregnancy_category =
| legal_AU = Unscheduled
| routes_of_administration = ]
| class = ]; ]
| ATC_prefix = R06
| ATC_suffix = AX26
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S2
| legal_AU_comment = / S4
| legal_BR = OTC
| legal_BR_comment =
| legal_CA = OTC | legal_CA = OTC
| legal_UK = POM | 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 = P
| legal_UK_comment = / P/ GSL<ref>{{cite web | title=Telfast 30mg Film-coated Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=25 October 2019 | url=https://www.medicines.org.uk/emc/product/5529/smpc | access-date=20 June 2021}}</ref><ref>{{cite web | title=Almerg 180 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | url=https://www.medicines.org.uk/emc/product/10147/smpc | access-date=20 June 2021}}</ref><ref>{{cite web | title=Fexofenadine Hydrochloride 120 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=22 March 2021 | url=https://www.medicines.org.uk/emc/product/10144/smpc | access-date=20 June 2021 | archive-date=24 June 2021 | archive-url=https://web.archive.org/web/20210624202243/https://www.medicines.org.uk/emc/product/10144/smpc | url-status=dead }}</ref>
| legal_US = OTC | legal_US = OTC
| legal_US_comment = / Rx-only<ref name="Allegra FDA label">{{cite web | title=Allegra (fexofenadine hydrochloride) tablet, orally disintegrating for oral use Allegra (fexofenadine hydrochloride) tablet, film coated for oral use Allegra (fexofenadine hydrochloride) suspension for oral useInitial U.S. Approval: 1996 | website=DailyMed | date=15 December 2008 | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=17669 | access-date=13 February 2022}}</ref><ref>{{cite web | title=Allegra Allergy- fexofenadine hydrochloride tablet, coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f061d6b1-89f7-4d5f-ac59-9c73408517c1 | access-date=12 February 2022}}</ref><ref>{{cite web | title = ALLEGRA (fexofenadine hydrochloride) Product Monograph | date = 7 November 2019 | publisher = Sanofi Consumer Health Inc. | url = http://products.sanofi.ca/en/allegra.pdf }}</ref>
| routes_of_administration = ]
| 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 = 30-41%<ref>{{cite journal | author = Lappin G, Shishikura Y, Jochemsen R, Weaver RJ, Gesson C, Houston B, Oosterhuis B, Bjerrum OJ, Rowland M, Garner C | title = Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability | journal = Eur J Pharm Sci | volume = 40 | issue = 2 | pages = 125–31 | year = 2010 | month = May | pmid = 20307657 | doi = 10.1016/j.ejps.2010.03.009}}</ref> | bioavailability = 30–41%<ref>{{cite journal | vauthors = Lappin G, Shishikura Y, Jochemsen R, Weaver RJ, Gesson C, Houston B, Oosterhuis B, Bjerrum OJ, Rowland M, Garner C | title = Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability | journal = European Journal of Pharmaceutical Sciences | volume = 40 | issue = 2 | pages = 125–131 | date = May 2010 | pmid = 20307657 | doi = 10.1016/j.ejps.2010.03.009 }}</ref>
| protein_bound = 60–70%<ref name=phk09>{{cite journal | vauthors = Smith SM, Gums JG | title = Fexofenadine: biochemical, pharmacokinetic and pharmacodynamic properties and its unique role in allergic disorders | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 5 | issue = 7 | pages = 813–822 | date = July 2009 | pmid = 19545214 | doi = 10.1517/17425250903044967 | s2cid = 19048690 }}</ref>
| protein_bound = 60-70%
| metabolism = ] (5% of dose) | metabolism = ] (≤5% of dose)<ref name=phk09/>
| metabolites =
| onset =
| elimination_half-life = 14.4 hours | elimination_half-life = 14.4 hours
| duration_of_action =
| excretion = Feces (~80%) and urine (~11%) as unchanged drug
| excretion = Feces (~80%) and urine (~10%) as unchanged drug<ref name=phk09/>


<!--Identifiers--> <!-- Identifiers -->
| index2_label = as HCl
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 83799-24-0 | CAS_number = 83799-24-0
| ATC_prefix = R06 | CAS_supplemental =
| ATC_suffix = AX26
| PubChem = 3348 | PubChem = 3348
| IUPHAR_ligand = 4819
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00950 | DrugBank = DB00950
Line 44: Line 75:
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07958 | KEGG = D07958
| ChEBI_Ref = {{ebicite|changed|EBI}} | KEGG2_Ref = {{keggcite|correct|kegg}}
| KEGG2 = D00671
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 5050 | ChEBI = 5050
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 914 | ChEMBL = 914
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =


<!--Chemical data--> <!-- Chemical and physical data -->
| IUPAC_name = (±)-4--butyl]-α, α-dimethyl benzeneacetic acid
| C=32 | H=39 | N=1 | O=4
| C=32 | H=39 | N=1 | O=4
| molecular_weight = 501.656
| smiles = O=C(O)C(c1ccc(cc1)C(O)CCCN2CCC(CC2)C(O)(c3ccccc3)c4ccccc4)(C)C | SMILES = O=C(O)C(c1ccc(cc1)C(O)CCCN2CCC(CC2)C(O)(c3ccccc3)c4ccccc4)(C)C
| InChI = 1/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)
| InChIKey = RWTNPBWLLIMQHL-UHFFFAOYAM
| StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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) | StdInChI = 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)
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RWTNPBWLLIMQHL-UHFFFAOYSA-N | StdInChIKey = RWTNPBWLLIMQHL-UHFFFAOYSA-N
}} }}
<!-- Definition and medical uses -->
'''Fexofenadine''', sold under the brand name '''Allegra''' among others,<ref name=Brands/> is an ] ] used in the treatment of allergy symptoms, such as ] and ].<ref>{{cite journal | vauthors = Bachert C | title = A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis | journal = Clinical Therapeutics | volume = 31 | issue = 5 | pages = 921–944 | date = May 2009 | pmid = 19539095 | doi = 10.1016/j.clinthera.2009.05.017 }}</ref>


Therapeutically, fexofenadine is a ] ] ]. It is classified as a second-generation antihistamine because it is less able to pass the ] and cause sedation, compared to first-generation antihistamines.<ref name="rhin11">{{cite journal | vauthors = Compalati E, Baena-Cagnani R, Penagos M, Badellino H, Braido F, Gómez RM, Canonica GW, Baena-Cagnani CE | title = Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials | journal = International Archives of Allergy and Immunology | volume = 156 | issue = 1 | pages = 1–15 | date = 2011 | pmid = 21969990 | doi = 10.1159/000321896 | doi-access = free }}</ref><ref name="rhin1">{{cite journal | vauthors = Dicpinigaitis PV, Gayle YE | title = Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function | journal = British Journal of Clinical Pharmacology | volume = 56 | issue = 5 | pages = 501–504 | date = November 2003 | pmid = 14651723 | pmc = 1884387 | doi = 10.1046/j.1365-2125.2003.01902.x }}</ref>
'''Fexofenadine''' (trade names '''Allegra''', '''Telfast''', '''Fastofen''', '''Tilfur''', '''Vifas''', '''Telfexo''', '''Allerfexo''') is an ] ] used in the treatment of ] and similar ] symptoms. It was developed as a successor of and alternative to ] (trade names include ''Triludan'' and ''Seldane''), an antihistamine that caused ] prolongation, potentially leading to ]. Fexofenadine, like other second- and third-generation ]s, does not readily cross the ], and so causes less drowsiness than first-generation ]-receptor antagonists. It works by being an ] to the ].<ref>{{cite pmid|16556272}}</ref>


<!-- Society and culture -->
It has been described as both a second-generation<ref name="pmid14651723">{{cite journal |author=Dicpinigaitis PV, Gayle YE |title=Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function |journal=British journal of clinical pharmacology |volume=56 |issue=5 |pages=501–4 |year=2003 |month=November |pmid=14651723 |pmc=1884387 |doi=10.1046/j.1365-2125.2003.01902.x}}</ref> and third-generation antihistamine.<ref name="pmid12575922">{{cite journal |author=Vena GA, Cassano N, Filieri M, Filotico R, D'Argento V, Coviello C |title=Fexofenadine in chronic idiopathic urticaria: a clinical and immunohistochemical evaluation |journal=Int J Immunopathol Pharmacol |volume=15 |issue=3 |pages=217–24 |year=2002 |pmid=12575922 }}</ref>
It was patented in 1979 and came into medical use in 1996.<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 on the ].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> Fexofenadine has been manufactured in generic form since 2011.<ref>{{cite web|url=http://www.drreddys.com/media/press-releases/aug30_2011.html |title=Dr. Reddy's announces the launch of Over-the-Counter Fexofenadine HCl and Pseudoephedrine HCl extended-release tablets |date=30 August 2011 |publisher=Dr. Reddy's Laboratories Ltd. |access-date=27 May 2016 |url-status=dead |archive-url=https://web.archive.org/web/20161012010000/http://www.drreddys.com/media/press-releases/aug30_2011.html |archive-date=12 October 2016 }}</ref> In 2022, it was the 257th most commonly prescribed medication in the United States, with more than 1{{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 = Fexofenadine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Fexofenadine | access-date = 30 August 2024 }}</ref>


==Indications== ==Medical uses==
Fexofenadine is indicated for the relief from physical symptoms associated with ] and treatment of ].<ref>{{cite web|author=March 22, 2011 |url=http://www.medicinenet.com/fexofenadine/article.htm |title=fexofenadine (Allegra) - drug class, medical uses, medication side effects, and drug interactions by |publisher=Medicinenet.com |date=2002-11-07 |accessdate=2011-03-22}}</ref> It is not a therapeutic drug and does not cure but rather prevents the aggravation of ] and ] and reduces the severity of the symptoms associated with those conditions, providing much relief from repeated sneezing, runny nose, itchy eyes and general body fatigue.<ref name="AustriaCodex">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2010|edition=2010/2011|language=German}}</ref><ref name="Arzneistoff-Profile">{{cite book|title=Arzneistoff-Profile|editor=Dinnendahl, V, Fricke, U|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=23|volume=2|isbn=978-3-7741-98-46-3|language=German}}</ref> Fexofenadine is used for relief from physical symptoms associated with seasonal ] and for treatment of hives, including chronic ].<ref name=rhin11/> It does not cure, but rather prevents the aggravation of allergic rhinitis and chronic idiopathic urticaria, and reduces the severity of the symptoms associated with those conditions, providing relief from repeated sneezing, runny nose, itchy eyes or skin, and general body fatigue. In a 2018 review, fexofenadine, along with ], ], and ], was cited to be a safe drug to use for individuals with inherited ].<ref>{{cite journal | vauthors = Welzel T, Ziesenitz VC, Seitz S, Donner B, van den Anker JN | title = Management of anaphylaxis and allergies in patients with long QT syndrome: A review of the current evidence | journal = Annals of Allergy, Asthma & Immunology | volume = 121 | issue = 5 | pages = 545–551 | date = November 2018 | pmid = 30059791 | doi = 10.1016/j.anai.2018.07.027 | doi-access = free }}</ref>


===Dosage=== === Efficacy ===
For the treatment of ], fexofenadine is similarly effective to ], but is associated with less drowsiness than cetirizine.<ref>{{cite journal | vauthors = Hampel F, Ratner P, Mansfield L, Meeves S, Liao Y, Georges G | title = Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine, 10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic rhinitis | journal = Annals of Allergy, Asthma & Immunology | volume = 91 | issue = 4 | pages = 354–361 | date = October 2003 | pmid = 14582814 | doi = 10.1016/S1081-1206(10)61682-1 }}</ref> Fexofenadine was also shown to inhibit ]-induced ] to a significantly greater degree than ] or ],<ref>{{cite journal | vauthors = Kruszewski J, Kłos K, Sułek K | title = | journal = Polski Merkuriusz Lekarski | volume = 21 | issue = 125 | pages = 443–448 | date = November 2006 | pmid = 17345837 | url = https://pubmed.ncbi.nlm.nih.gov/17345837/ }}</ref> but was slightly less effective than ].<ref>{{cite journal | vauthors = Grant JA, Riethuisen JM, Moulaert B, DeVos C | title = A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects | journal = Annals of Allergy, Asthma & Immunology | volume = 88 | issue = 2 | pages = 190–197 | date = February 2002 | pmid = 11868924 | doi = 10.1016/S1081-1206(10)61995-3 }}</ref>
* Children of 12 years and older, adults: 60&nbsp;mg twice daily ''or'' 180&nbsp;mg once daily
* Elderly: Starting dose: 60&nbsp;mg once daily


Fexofenadine at doses above 120&nbsp;mg a day does not appear to provide additional efficacy in the treatment of allergic rhinitis.<ref>{{cite journal | vauthors = Casale TB, Andrade C, Qu R | title = Safety and efficacy of once-daily fexofenadine HCl in the treatment of autumn seasonal allergic rhinitis | journal = Allergy and Asthma Proceedings | volume = 20 | issue = 3 | pages = 193–198 | date = 1999 | pmid = 10389553 | doi = 10.2500/108854199778553046 }}</ref><ref>{{cite journal | vauthors = Howarth PH, Stern MA, Roi L, Reynolds R, Bousquet J | title = Double-blind, placebo-controlled study comparing the efficacy and safety of fexofenadine hydrochloride (120 and 180 mg once daily) and cetirizine in seasonal allergic rhinitis | journal = The Journal of Allergy and Clinical Immunology | volume = 104 | issue = 5 | pages = 927–933 | date = November 1999 | pmid = 10550734 | doi = 10.1016/s0091-6749(99)70070-9 | doi-access = free }}</ref>
Fexofenadine is not well examined for children under 12 years.<ref name="AustriaCodex" />

===Dosage forms===
* Suspension: 6&nbsp;mg/mL (300 mL) <ref name="Allegra_Insert">Allegra (fexofenadine hydrochloride) tablets, ODT, and oral suspension package insert. Bridgewater, NJ: Sanofi-Aventis; 2008 Dec.</ref>
* Tablet: 30&nbsp;mg, 60&nbsp;mg, 180&nbsp;mg<ref name="Allegra_Insert" />
* Orally-disintegrating tablet: 30&nbsp;mg<ref name="Allegra_Insert" />
* Some preparations are combined with 120&nbsp;mg (12 hour extended release dosage form) or 240&nbsp;mg (24 hour extended release dosage form) of ] as a decongestant.<ref>Allegra D-12 Hour (fexofenadine hcl and pseudoephedrine hcl) tablets, extended release package insert. Bridgewater, NJ: Sanofi-Aventis; 2009 Dec.</ref><ref>Allegra-D 24 Hour (fexofenadine hcl and pseudoephedrine hcl) tablets, extended release package insert. Bridgewater, NJ: Sanofi-Aventis; 2009 Dec.</ref>


==Side effects== ==Side effects==
The most common ]s include headache, back and muscle pain, ] or pinpoint pupils, nausea, drowsiness, and menstrual cramps. ] and ] have also been rarely reported. The most common side effects demonstrated during clinical trials were ], ], ], and ] for children ages 6 to 11 and ] for children ages 6 months to 5 years.<ref name="Allegra FDA label"/>
The most common side effects are ], ], ], ] and ]; ] ]s and frequent ] are seen in less than 1% of patients. In studies, all of these effects occurred with similar frequencies as under ].<ref name="AustriaCodex" /><ref name="Arzneistoff-Profile" />


==Overdose== ==Overdose==
The safety profile of fexofenadine is quite favorable, as no ] or ] effects have been shown to occur even when taking 10 times the recommended dose.<ref>{{cite journal | vauthors = Philpot EE | title = Safety of second-generation antihistamines | journal = Allergy and Asthma Proceedings | volume = 21 | issue = 1 | pages = 15–20 | date = Jan–Feb 2000 | pmid = 10748947 | doi = 10.2500/108854100778249033 }}</ref> Research on humans ranges from a single 800-mg dose, to a twice-daily, 690-mg dose for a month, with no clinically significant adverse effects, when compared to a ]. No deaths occurred in testing on mice, at 5000&nbsp;mg/kg body weight, which is 110 times the maximum recommended dose for an adult human.<ref name="Allegra FDA label"/> If an overdose were to occur, supportive measures are recommended. Theoretically, an overdose could present as dizziness, dry mouth, and/or drowsiness, consistent with an exaggeration of the usual side effects. ] does not appear to be an effective means of removing fexofenadine from the blood.<ref name="Allegra FDA label"/>
Reports of fexofenadine overdose are infrequent, and because of this, the effects are not well established. No deaths occurred in testing on mice, at 5000&nbsp;mg/kg body weight, which is one-hundred and ten times the maximum recommended dose for an adult human. Further research shows no deaths in rats at the same concentration, which equates four hundred times the recommended dose in an adult human.


==Pharmacology==
Research on humans ranges from a single 800&nbsp;mg dose, to a twice-daily 690&nbsp;mg dose for a month, with no clinically significant adverse effects, when compared to a placebo.<ref name="AustriaCodex" />
===Pharmacodynamics===
Fexofenadine is a ] ] ]. Blockage prevents the activation of the H<sub>1</sub> receptors by ], preventing the symptoms associated with allergies from occurring. Fexofenadine does not readily cross the ], so is less likely to cause drowsiness in comparison to other antihistamines that readily cross that barrier (i.e., first-generation antihistamines such as ]). In general, fexofenadine takes about an hour to take effect, though this may be affected by the choice of dosage form and the presence of certain foods.<ref name="Allegra FDA label"/><ref>{{cite journal | vauthors = Stoltz M, Arumugham T, Lippert C, Yu D, Bhargava V, Eller M, Weir S | title = Effect of food on the bioavailability of fexofenadine hydrochloride (MDL 16455A) | journal = Biopharmaceutics & Drug Disposition | volume = 18 | issue = 7 | pages = 645–648 | date = October 1997 | pmid = 9330784 | doi = 10.1002/(SICI)1099-081X(199710)18:7<645::AID-BDD50>3.0.CO;2-3 }}</ref>


Fexofenadine also exhibits no ], ], ], ], or ] receptor-blocking effects.<ref name="Allegra FDA label"/>
==Mechanism of action==
Fexofenadine is a second-generation selectively peripheral H1-blocker of the GI tract, large blood vessels, and bronchial smooth muscle. Blockage prevents the activation of the H1 receptors by ], preventing the symptoms associated with allergies from occurring. Fexofenadine cannot cross the blood-brain barrier and therefore does not cause drowsiness. It also exhibits no ], ], alpha1-adrenergic, or beta-adrenergic-receptor-blocking effects.<ref>, ''DrugBank'', accessed June 13, 2011.</ref>


==Pharmacokinetics== ===Pharmacokinetics===
* ]: After oral application, maximum plasma concentrations are reached after 2–3 hours. Fexofenadine should not be taken with a high-fat meal, as mean concentrations of fexofenadine in the bloodstream are seen to be reduced by 20–60% depending on the form of medication (tablet, ODT, or suspension).<ref name="Allegra FDA label"/>
After oral application, about one-third of the drug is absorbed into the bloodstream. Maximum plasma concentrations are reached after one to three hours. Fexofenadine is effective from one hour to 24 hours after application, with maximum effectiveness after six hours.<ref name="Arzneistoff-Profile" />
* ]: Fexofenadine is 60–70% bound to plasma proteins, mostly albumin.<ref name="Allegra FDA label"/>
* ]: Fexofenadine is a substrate of CYP3A4, but only about 5% is metabolized by the liver, indicating that hepatic metabolism is relatively minor in clearance from the body.<ref name="Allegra FDA label"/>
* ]: Most of the substance is eliminated unchanged via the feces (80%) and urine (11–12%).<ref name="Allegra FDA label"/>


== Interactions ==
Only a small percentage is metabolized in the liver, mainly to the ] and to ]; both are pharmacologically irrelevant. Most of the substance is eliminated unchanged via the feces (80%) and urine (11–12%).<ref name="Arzneistoff-Profile" />


Taking ] or ] while taking fexofenadine does increase the ] levels of fexofenadine, but this increase does not influence the ]. The reason for this effect is likely due to transport-related effects, specifically involving p-glycoprotein (p-gp).<ref name="Allegra FDA label" /> Both erythromycin and ketoconazole are inhibitors of p-gp, a transporter protein involved in preventing the intestinal absorption of fexofenadine. When p-gp is inhibited, fexofenadine may be better absorbed by the body, increasing its plasma concentration by more than intended.{{Citation needed|date=July 2020}}
==Interactions==
] and ] increase the plasma levels of fexofenadine two- to threefold without influencing the QT interval. The reason for this effect is not well understood and could be caused by increased absorption or reduced gastrointestinal or ] secretion.<ref name="Arzneistoff-Profile" /><ref name="Arzneimittel-Interaktionen">{{cite book|title=Arzneimittel-Interaktionen|editor=Klopp, T|publisher=Arbeitsgemeinschaft für Pharmazeutische Information|year=2010|edition=2010/2011|isbn=978-3-85200-207-1|language=German}}</ref>


Fexofenadine is not to be taken with apple, orange, or grapefruit juice because they could decrease absorption of the drug. Therefore, it should be taken with water.<ref name="Allegra FDA label"/> Grapefruit juice can significantly reduce the plasma concentration of fexofenadine.<ref>{{cite journal | vauthors = Shirasaka Y, Mori T, Murata Y, Nakanishi T, Tamai I | title = Substrate- and dose-dependent drug interactions with grapefruit juice caused by multiple binding sites on OATP2B1 | journal = Pharmaceutical Research | volume = 31 | issue = 8 | pages = 2035–2043 | date = August 2014 | pmid = 24549825 | doi = 10.1007/s11095-014-1305-7 | s2cid = 17532347 }}</ref>
]s containing ] or ] reduce the absorption of fexofenadine.<ref name="Arzneistoff-Profile" /> Fexofenadine is not to be taken with fruit juices, as decrease of the absorption of the drug could be effected.<ref>{{cite journal | pmid = 15570603 | year = 2005 | last1 = Kamath | first1 = AV | last2 = Yao | first2 = M | last3 = Zhang | first3 = Y | last4 = Chong | first4 = S | title = Effect of fruit juices on the oral bioavailability of fexofenadine in rats | volume = 94 | issue = 2 | pages = 233–9 | doi = 10.1002/jps.20231 | journal = Journal of pharmaceutical sciences}}</ref> Grapefruit juices can significantly reduce plasma concentration of fexofenadine.


]s containing ] or ] should not be taken within 15 minutes of fexofenadine, as they reduce its absorption by almost 50%.<ref name="Allegra FDA label"/> This is not thought to be due to a change in pH (in fact, absorption can actually ''increase'' under increasingly alkaline pH), but rather due to the formation of metal complexes with charged/polar moieties on fexofenadine. As suggested by Shehnaza ''et al'' (2014), various sites of the molecule are thought to be responsible for this interaction, including the piperidine nitrogen, the carboxylic acid (-COOH) group, and both hydroxyl (-OH) groups.<ref name="FXF-Antacid Intxn">{{cite journal| vauthors = Shehnaz H, Haider A, Arayne MS, Sultana N |title=Carboxyterfenadine antacid interaction monitoring by UV spectrophotometry and RP-HPLC techniques|journal=Arabian Journal of Chemistry|date=Nov 2014|volume=7|issue=5|pages=839–845|doi=10.1016/j.arabjc.2013.01.011|doi-access=free}}</ref>
While ] (hypericum perforatum) and its preparations do interact with fexofenadine, since fexofenadine is a P-glycoprotein substrate and ] is an inducer, this interaction is deemed "unlikely to cause problems" - see .


==History== ==History==
The older antihistaminic agent ] was found to ] into the related ], fexofenadine. Fexofenadine was found to retain all of the biological activity of its parent while giving fewer adverse reactions in patients, so terfenadine was replaced in the market by its ].<ref name=Lednicer1999>{{cite book The older antihistaminic agent ] was found to ] into the related ], fexofenadine. Fexofenadine was found to retain all of the biological activity of its parent while giving fewer adverse reactions in patients, so terfenadine was replaced in the market by its ].<ref name=Lednicer1999>{{cite book |author= Daniel Lednicer |title= The Organic Chemistry of Drug Synthesis |publisher= Wiley Interscience |volume= 6 |year= 1999 |location= New York |pages= 38–40 |isbn= 978-0-471-24510-0}}</ref> Fexofenadine was originally synthesized in 1993 by ]-based ] company ], which then sold the development rights to ] (now part of ]), and was later approved by the U.S. ] (FDA) in 1996. Albany Molecular Research Inc. (AMRI) holds the patents to the intermediates and production of fexofenadine HCl, along with Roussel. Since that time, it has achieved ] status with global sales of US$1.87B in 2004 (with $1.49B coming from the United States). AMRI received royalty payments from Aventis which enabled the growth of AMRI.{{citation needed|date=July 2020}}
| author = Daniel Lednicer
| title = The Organic Chemistry of Drug Synthesis
| publisher = Wiley Interscience
| volume = 6
| year = 1999
| location = New York
| pages = 38–40
| isbn = 0-471-24510-0 }}</ref> Fexofenadine was originally synthesized in 1993 by ]-based ] company ], which then sold the development rights to ] (now part of ]), and was later approved by the ] (FDA) in 1996. AMRI holds the patents to the intermediates and production of fexofenadine HCl along with Roussel. Since that time, it has achieved ] status with global sales of $1.87B USD in 2004 (with $1.49B USD coming from the ]). AMRI received royalty payments from Aventis that enabled the growth of AMRI.


In January 2011, the FDA approved over-the-counter sales of fexofenadine in the United States, and Sanofi Aventis' version became available in March 2011.<ref name="Sanofi-Aventis">{{cite web |url=http://www.allegra.com/faqs.aspx |title=Allegra FAQs |publisher=Sanofi-Aventis |access-date=5 July 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110520065527/http://allegra.com/faqs.aspx |archive-date=20 May 2011 }}</ref> In December 2020, the MHRA reclassified fexofenadine from prescription only to allow general sales in the United Kingdom.<ref>{{cite web|url=https://www.gov.uk/government/publications/public-assessment-report-of-the-reclassification-of-allevia-120mg-tablets/par-reclassification-of-allevia-120mg-tablets-from-prescription-only-medicine-pom-to-general-sales-list-gsl|title=PAR: Reclassification of Allevia 120mg tablets from Prescription Only Medicine (POM) to General Sales List (GSL)|work=MHRA|date=22 December 2020}}</ref>
On January 25, 2011, the FDA approved over-the-counter sales of fexofenadine in the United States, and Sanofi-Aventis' version became available on March 4, 2011.<ref name=Sanofi-Aventis>{{cite web
|url=http://www.allegra.com/faqs.aspx
|title=Allegra &#124; FAQs
|publisher=Sanofi-Aventis
|accessdate=5 July 2011}}</ref>


==Society and culture==
==Synthesis==
===Brand names===
Fexofenadine may be synthesized as shown from piperidine-4-carboxylate ester and 4-bromophenylacetonitrile.<ref name=Lednicer1999>{{cite book
Fexofenadine is marketed under many brand names worldwide.<ref name=Brands>{{cite web|title=Fexofenadine - international brand names|url=https://www.drugs.com/international/fexofenadine.html|publisher=Drugs.com|access-date=18 January 2017}}</ref>
| author = Daniel Lednicer
| title = The Organic Chemistry of Drug Synthesis
| publisher = Wiley Interscience
| volume = 6
| year = 1999
| location = New York
| pages =
| isbn = 0-471-24510-0 }}</ref><ref>{{cite journal | journal = J. Org. Chem. | year = 1994 | volume = 59 | pages = 2620–22 | doi = 10.1021/jo00088a056 | title = A facile synthesis of an oxidation product of terfenadine | first3 = G | last3 = Just | first2 = RJ | last2 = Hambalek | last1 = Kawai | first1 = SH | month = May | issue = 9 }}</ref>


As of January 2017, it is marketed as a ] with ] under brand names including Alerfedine D, Allegra-D, Allergyna-D, Allevia, Altiva-D, Dellegra, Fexo Plus, Fexofed, Fixal Plus, Ridrinal D, Rinolast D, Telfast D, and Treathay.<ref name=Brands/>
:]


As of January 2017, it is marketed as a combination drug with ] under brand names including Fexokast, Histakind-M, Monten-FX, Montolife-FX, Montair-FX and Novamont-FX.<ref name=Brands/>
To produce the piperidine piece, two phenyl groups are first introduced using a ] on the ], giving a tertiary ]. The ] group is then ] with a ] ], then the aldehyde is recovered by deprotection with acid. The remaining piece of the molecule is produced by a double alkylation by ] of the ] derived from the ]. The nitrile group is then hydrolyzed to a ]. The aryl bromide is then lithiated to produce the ] compound, which can be coupled with the aldehyde piece to give (after workup) fexofenadine.


==References== == References ==
{{reflist|2}} {{Reflist}}


{{refbegin}} {{Antihistamines}}
{{Histamine receptor modulators}}
* Biological effects: {{cite journal | journal = ] | year = 1993 | volume = 44 | pages = 1240–5 | pmid = 8264561 | last1 = Rampe | first1 = D | last2 = Wible | first2 = B | last3 = Brown | first3 = AM | last4 = Dage | first4 = RC | title = Effects of terfenadine and its metabolites on a delayed rectifier K+ channel cloned from human heart | issue = 6 | month = December }}
{{Portal bar | Medicine}}
{{refend}}
{{Authority control}}

==External links==
* (UK patient information leaflet)
*
* {{Medicinenet|fexofenadine}}

{{Histaminergics}}


]
]
]
] ]
] ]
]
] ]
] ]
]

]
]
]
]
]
]
]
]
]
]
]
]
]