Editing Desloratadine

{{Short description|Allergy medication}}
{{Use dmy dates|date=May 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| verifiedrevid = 460777963
| image = Desloratadine.svg
| image_class = skin-invert-image
| width = 222
| alt = 
| image2 = Desloratadine 3D ball-and-stick.png
| alt2 = 

<!-- Clinical data -->
| pronounce = 
| tradename = Aerius, others<ref name="murdoch">{{cite journal | vauthors = Murdoch D, Goa KL, Keam SJ | title = Desloratadine: an update of its efficacy in the management of allergic disorders | journal = Drugs | volume = 63 | issue = 19 | pages = 2051–2077 | date = 7 April 2003 | pmid = 12962522 | doi = 10.2165/00003495-200363190-00010 | s2cid = 195689362 }}</ref>
| Drugs.com = {{drugs.com|monograph|desloratadine}}
| MedlinePlus = a602002
| DailyMedID = Desloratadine
| pregnancy_AU = B1
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Anti-allergic agent]]
| ATC_prefix = R06
| ATC_suffix = AX27
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = S2
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = OTC
| 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 = POM
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = <ref name="Clarinex FDA label">{{cite web | title=Clarinex- desloratadine tablet, film coated | website=DailyMed | date=14 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c671342e-69a2-4ca5-abc2-8166ed4240d4 | access-date=18 May 2024}}</ref><ref>{{cite web | title=Clarinex-D 12 HOUR- desloratadine and pseudoephedrine sulfate tablet, extended release | website=DailyMed | date=14 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af66b7a-4ab8-40d8-abdd-22d3310228a8 | access-date=18 May 2024}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = /{{nbsp}}OTC<ref name="Desloratadine ratiopharm EPAR">{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/desloratadine-ratiopharm|title=Desloratadine ratiopharm EPAR |website=[[European Medicines Agency]] (EMA) | date=13 January 2012 | access-date=23 March 2025 }}</ref><ref name="Neoclarityn EPAR">{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/neoclarityn|title=Neoclarityn EPAR |website=[[European Medicines Agency]] (EMA) | date=15 January 2001 | access-date=23 March 2025 }}</ref><ref>{{cite web | title=Aerius EPAR | website=[[European Medicines Agency]] (EMA) | date=15 January 2001 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/aerius | access-date=24 March 2025}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = Rapidly absorbed
| protein_bound = 83 to 87%
| metabolism = [[UGT2B10]], [[CYP2C8]]
| metabolites = 3-Hydroxydesloratadine
| onset = within 1 hour
| elimination_half-life = 27 hours, 33.7 hours in elderly patients<ref name="Clarinex FDA label" />
| duration_of_action = up to 24 hours
| excretion = 40% as conjugated metabolites into urine<br />Similar amount into the feces

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 100643-71-8
| CAS_supplemental = 
| PubChem = 124087
| IUPHAR_ligand = 7157
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00967
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 110575
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = FVF865388R
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03693
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 291342
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1172
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = descarboethoxyloratadine<ref name="loratadine-fda-2000">{{cite web |author1=Schering Corporation |title=CLARITIN brand of Loratadine - Full Prescribing Information (US FDA) |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20641s7lbl.pdf |website=US FDA |access-date=17 May 2024 |date=2000 |quote="loratadine is metabolized to descarboethoxyloratadine predominantly by cytochrome P450 3A4 (CYP3A4) and, to a lesser extent, by cytochrome P450 2D6 (CYP2D6)."}}</ref>

<!-- Chemical and physical data -->
| IUPAC_name = 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5''H''-benzo[5,6]cyclohepta[1,2-b]pyridine
| C=19 | H=19 | Cl=1 | N=2
| smiles = Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H19ClN2/c20-16-5-6-17-15(12-16)4-3-14-2-1-9-22-19(14)18(17)13-7-10-21-11-8-13/h1-2,5-6,9,12,21H,3-4,7-8,10-11H2
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JAUOIFJMECXRGI-UHFFFAOYSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Desloratadine''' sold under the brand name '''Aerius''' among others, is a [[tricyclic]] [[H1 antagonist|H<sub>1</sub> inverse agonist]] that is used to treat [[allergy|allergies]]. It is an [[active metabolite]] of [[loratadine]].

<!-- Society and culture -->
It was patented in 1984 and came into medical use in 2001.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=549 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA549 }}</ref> It was brought to the market in the US by Schering Corporation, later named [[Schering-Plough]].<ref name="Clarinex FDA label" />

== Medical uses ==
Desloratadine is used to treat [[allergic rhinitis]], [[nasal congestion]] and [[chronic idiopathic urticaria]] ([[hives]]).<ref name=AFP2003>{{cite journal | vauthors = See S | title = Desloratadine for allergic rhinitis | journal = American Family Physician | volume = 68 | issue = 10 | pages = 2015–2016 | date = November 2003 | pmid = 14655812 | url = http://www.aafp.org/afp/20031115/steps.html | access-date = 1 August 2005 | archive-date = 24 July 2005 | archive-url = https://web.archive.org/web/20050724082052/http://www.aafp.org/afp/20031115/steps.html | url-status = dead }}</ref> It is the major [[metabolite]] of [[loratadine]] and the two drugs are similar in safety and effectiveness.<ref name=AFP2003/> Desloratadine is available in many dosage forms and under many brand names worldwide.<ref>{{cite web | work = Drugs.com | url = https://www.drugs.com/international/desloratadine.html | title = Desloratadine | access-date = 4 May 2015 }}</ref>

An emerging indication for desloratadine is in the treatment of [[acne]], as an inexpensive adjuvant to [[isotretinoin]] and possibly as maintenance therapy or monotherapy.<ref name=JEADV2014>{{cite journal | vauthors = Lee HE, Chang IK, Lee Y, Kim CD, Seo YJ, Lee JH, Im M | title = Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study | journal = Journal of the European Academy of Dermatology and Venereology | volume = 28 | issue = 12 | pages = 1654–1660 | date = December 2014 | pmid = 25081735 | doi = 10.1111/jdv.12403 | s2cid = 3406128 }}</ref><ref name=DC2016>{{cite journal | vauthors = Layton AM | title = Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 147–157 | date = April 2016 | pmid = 27015774 | doi = 10.1016/j.det.2015.11.008 }}</ref>

== Side effects ==
The most common side-effects are [[fatigue (medical)|fatigue]] (1.2%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453"/>), [[dry mouth]] (3%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453">{{cite journal | vauthors = González-Núñez V, Valero A, Mullol J | title = Safety evaluation of desloratadine in allergic rhinitis | journal = Expert Opinion on Drug Safety | volume = 12 | issue = 3 | pages = 445–453 | date = May 2013 | pmid = 23574541 | doi = 10.1517/14740338.2013.788148 | publisher = Informa Healthcare | s2cid = 40472187 }}</ref>), and [[headache]] (0.6%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453"/>).<ref name=AFP2003/>

== Interactions ==
Co-administration with [[erythromycin]], [[ketoconazole]], [[azithromycin]], [[fluoxetine]], or [[cimetidine]] resulted in elevated blood plasma concentrations of desloratadine and its [[metabolite]] 3-hydroxydesloratadine in studies. However, no clinically relevant changes were observed.<ref name="Clarinex FDA label" /><ref name="EPAR">{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000313/WC500025540.pdf|title=Aerius: EPAR – Product Information|publisher=[[European Medicines Agency]]|access-date=21 January 2022|archive-date=5 July 2019|archive-url=https://web.archive.org/web/20190705132734/https://www.ema.europa.eu/en/documents/product-information/aerius-epar-product-information_en.pdf|url-status=dead}}</ref>

== Pharmacology ==
=== Pharmacodynamics ===
Desloratadine is a selective H<sub>1</sub>-[[antihistamine]] which functions as an [[inverse agonist]] at the [[HRH1|histamine H<sub>1</sub> receptor]].<ref name="Desloratedine">{{cite journal | vauthors = Canonica GW, Blaiss M | title = Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence | journal = The World Allergy Organization Journal | volume = 4 | issue = 2 | pages = 47–53 | date = February 2011 | pmid = 23268457 | pmc = 3500039 | doi = 10.1097/WOX.0b013e3182093e19 }}</ref>

At very high doses, is also an [[receptor antagonist|antagonist]] at various subtypes of the [[muscarinic acetylcholine receptor]]s. This effect is not relevant for the drug's action at therapeutic doses.<ref>{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000313/WC500022748.pdf|title=Aerius: EPAR – Scientific Discussion|publisher=[[European Medicines Agency]]|date=3 April 2006|access-date=13 October 2017|archive-date=16 March 2018|archive-url=https://web.archive.org/web/20180316170856/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000313/WC500022748.pdf|url-status=dead}}</ref>

=== Pharmacokinetics ===
Desloratadine is well absorbed from the gut and reaches highest [[blood plasma]] concentrations after about three hours. In the bloodstream, 83 to 87% of the substance are bound to [[plasma protein]]s.<ref name="EPAR" />

Desloratadine is metabolized to 3-hydroxydesloratadine in a three-step sequence in normal metabolizers. First, N-glucuronidation of desloratadine by [[UGT2B10]]; then, 3-hydroxylation of desloratadine N-glucuronide by [[CYP2C8]]; and finally, a non-enzymatic deconjugation of 3-hydroxydesloratadine N-glucuronide.<ref name="kazmi-april-2015">{{cite journal | vauthors = Kazmi F, Barbara JE, Yerino P, Parkinson A | title = A long-standing mystery solved: the formation of 3-hydroxydesloratadine is catalyzed by CYP2C8 but prior glucuronidation of desloratadine by UDP-glucuronosyltransferase 2B10 is an obligatory requirement | journal = Drug Metabolism and Disposition | volume = 43 | issue = 4 | pages = 523–533 | date = April 2015 | pmid = 25595597 | doi = 10.1124/dmd.114.062620 }}</ref><ref name="further characterization">{{cite journal | vauthors = Kazmi F, Yerino P, Barbara JE, Parkinson A | title = Further Characterization of the Metabolism of Desloratadine and Its Cytochrome P450 and UDP-glucuronosyltransferase Inhibition Potential: Identification of Desloratadine as a Relatively Selective UGT2B10 Inhibitor | journal = Drug Metabolism and Disposition | volume = 43 | issue = 9 | pages = 1294–1302 | date = September 2015 | pmid = 26135009 | doi = 10.1124/dmd.115.065011 | doi-access = free }}</ref> Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a [[biological half-life|half-life]] of 27 hours in normal metabolizers.<ref name="EPAR" /><ref name="Drugs.com">{{cite web | title=Desloratadine Monograph for Professionals | website=Drugs.com | date=22 October 2024 | url=https://www.drugs.com/monograph/desloratadine.html | access-date=24 March 2025}}</ref>

[[File:3-Hydroxydesloratadine skeletal.svg|class=skin-invert-image|thumb|left|3-Hydroxydesloratadine is the main [[metabolite]].]]

It exhibits only peripheral activity since it does not readily cross the [[blood–brain barrier]]; hence, it does not normally cause [[drowsiness]] because it does not readily enter the [[central nervous system]].<ref>{{cite journal | vauthors = Mann RD, Pearce GL, Dunn N, Shakir S | title = Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice | journal = BMJ | volume = 320 | issue = 7243 | pages = 1184–1186 | date = April 2000 | pmid = 10784544 | pmc = 27362 | doi = 10.1136/bmj.320.7243.1184 }}</ref>

Desloratadine does not have a strong effect on a number of tested enzymes in the [[cytochrome P450]] system. It was found to weakly inhibit [[CYP2B6]], [[CYP2D6]], and [[CYP3A4]]/[[CYP3A5]], and not to inhibit [[CYP1A2]], [[CYP2C8]], [[CYP2C9]], or [[CYP2C19]]. Desloratadine was found to be a potent and relatively selective inhibitor of [[UGT2B10]], a weak to moderate inhibitor of [[UGT2B17]], [[UGT1A10]], and [[UGT2B4]], and not to inhibit [[UGT1A1]], [[UGT1A3]], [[UGT1A4]], [[UGT1A6]], [[UGT1A9]], [[UGT2B7]], [[UGT2B15]], [[UGT1A7]], and [[UGT1A8]].<ref name="further characterization" />

{{clear left}}

=== Pharmacogenomics ===
2% of [[Caucasian race|Caucasian]]s and 18% of people from African descent are desloratadine [[poor metabolizer]]s. In these people, the drug reaches threefold higher plasma concentrations at seven hours after intake, and it has a half-life of 89 hours (compared to a 27-hour half-life in normal metabolizers). Adverse effects were reported at similar rates in poor metabolizers, suggesting that it is not clinically relevant.<ref name="EPAR" /><ref name="Drugs.com" />

== References ==
{{Reflist}}

== Further reading ==
* {{cite journal | vauthors = Baena-Cagnani CE | title = Desloratadine activity in concurrent seasonal allergic rhinitis and asthma | journal = Allergy | volume = 56 Suppl 65 | issue = | pages = 21–7 | date = 2001 | pmid = 11243501 | doi = 10.1111/j.1398-9995.2001.00001.x-i1 }}
* {{cite journal | vauthors = Devillier P, Roche N, Faisy C | title = Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review | journal = Clinical Pharmacokinetics | volume = 47 | issue = 4 | pages = 217–30 | date = 2008 | pmid = 18336052 | doi = 10.2165/00003088-200847040-00001 }}
* {{cite journal | vauthors = Geha RS, Meltzer EO | title = Desloratadine: A new, nonsedating, oral antihistamine | journal = The Journal of Allergy and Clinical Immunology | volume = 107 | issue = 4 | pages = 751–62 | date = April 2001 | pmid = 11295678 | doi = 10.1067/mai.2001.114239 }}
* {{cite journal | vauthors = Henz BM | title = The pharmacologic profile of desloratadine: a review | journal = Allergy | volume = 56 Suppl 65 | issue = | pages = 7–13 | date = 2001 | pmid = 11243504 | doi = 10.1034/j.1398-9995.2001.00101.x }}

{{Antihistamines}}
{{Histaminergics}}
{{Tricyclics}}
{{Schering-Plough}}
{{Portal bar | Medicine}}
{{Authority control}}

[[Category:Benzocycloheptapyridines]]
[[Category:Chloroarenes]]
[[Category:H1 receptor antagonists]]
[[Category:Human drug metabolites]]
[[Category:Peripherally selective drugs]]
[[Category:Piperidines]]
[[Category:Drugs developed by Schering-Plough]]
[[Category:Drugs developed by Merck & Co.]]