Desloratadine

{{Infobox drug

| verifiedrevid = 460777963

| image = Desloratadine.svg

| image_class = skin-invert-image

| width = 222

| alt =

| image2 = Desloratadine 3D ball-and-stick.png

| alt2 =

| pronounce =

| tradename = Aerius, others{{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 }}

| Drugs.com = {{drugs.com|monograph|desloratadine}}

| MedlinePlus = a602002

| DailyMedID = Desloratadine

| pregnancy_AU = B1

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = By mouth

| class = Second-generation antihistamine

| ATC_prefix = R06

| ATC_suffix = AX27

| ATC_supplemental =

| legal_AU = S2

| legal_AU_comment =

| legal_BR =

| legal_BR_comment =

| legal_CA = OTC

| legal_CA_comment =

| legal_DE =

| legal_DE_comment =

| legal_NZ =

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| legal_UK = POM

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = {{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}}{{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}}

| legal_EU = Rx-only

| legal_EU_comment = /{{nbsp}}OTC{{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 }}{{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 }}{{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}}

| legal_UN =

| legal_UN_comment =

| legal_status =

| bioavailability = Rapidly absorbed

| protein_bound = 83–87%

| metabolism = UGT2B10, CYP2C8

| metabolites = 3-Hydroxydesloratadine

| onset = within 1 hour

| elimination_half-life = 27 hours, 33.7 hours in elderly patients

| duration_of_action = up to 24 hours

| excretion = 40% as conjugated metabolites into urine
Similar amount into the feces

| 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{{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)."}}

| IUPAC_name = 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5H-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 =

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}}

Desloratadine sold under the brand name Aerius among others, is a tricyclic H₁ inverse agonist that is used to treat allergies. It is an active metabolite of loratadine.

It was patented in 1984 and came into medical use in 2001.{{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 }} It was brought to the market in the US by Schering Corporation, later named Schering-Plough.

Medical uses

Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives).{{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 }} It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness. Desloratadine is available in many dosage forms and under many brand names worldwide.{{cite web | work = Drugs.com | url = https://www.drugs.com/international/desloratadine.html | title = Desloratadine | access-date = 4 May 2015 }}

An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.{{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 }}{{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 }}

Side effects

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

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.{{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}}

Pharmacology

= Pharmacodynamics =

Desloratadine is a selective H₁-antihistamine which functions as an inverse agonist at the histamine H₁ receptor.{{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 }}

At very high doses, is also an antagonist at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses.{{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}}

= 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 proteins.

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.{{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 }}{{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 }} Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.{{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}}

File:3-Hydroxydesloratadine skeletal.svg.]]

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.{{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 }}

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.

= Pharmacogenomics =

2% of Caucasians and 18% of people from African descent are desloratadine poor metabolizers. 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.