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{{Short description|Allergy medication}}
{{Drugbox
{{Use dmy dates|date=May 2024}}
| verifiedrevid = 443568675
{{cs1 config |name-list-style=vanc |display-authors=6}}
| IUPAC_name = 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5''H''-benzo[5,6]cyclohepta[1,2-b]pyridine
{{Infobox drug
| verifiedrevid = 460777963
| image = Desloratadine.svg
| image = Desloratadine.svg
| image_class = skin-invert-image
| image2 = Desloratadine2.png
| width = 222

| alt =
| image2 = Desloratadine 3D ball-and-stick.png
| tradename = Clarinex
| image_class2 = bg-transparent
| alt2 =
| pronounce =
| tradename = Aerius, Clarinex, 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}}
| Drugs.com = {{drugs.com|monograph|desloratadine}}
| MedlinePlus = a602002
| MedlinePlus = a602002
| DailyMedID = Desloratadine
| licence_EU = Aerius
| licence_US = Desloratadine
| pregnancy_AU = B1
| pregnancy_AU = B1
| pregnancy_AU_comment =
| pregnancy_US = C
| pregnancy_category =
| pregnancy_category =
| routes_of_administration = [[Oral 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 =
| legal_NZ_comment =
| legal_UK = POM
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only
| 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_status =
| legal_EU = Rx-only
| routes_of_administration = oral
| 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%
| bioavailability = Rapidly absorbed
| metabolism = [[UGT2B10]], [[CYP2C8]]
| protein_bound = 85%
| metabolites = 3-Hydroxydesloratadine
| metabolism = Liver
| onset = within 1 hour
| elimination_half-life = 27 hours
| elimination_half-life = 27 hours, 33.7 hours in elderly patients
| excretion = 40% as conjugated metabolites into urine
Similar amount into the feces
| duration_of_action = up to 24 hours
| excretion = 40% as conjugated metabolites into urine
Similar amount into the feces


| CAS_number_Ref = {{cascite|correct|??}}
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number = 100643-71-8
| CAS_number = 100643-71-8
| ATC_prefix = R06
| CAS_supplemental =
| ATC_suffix = AX27
| PubChem = 124087
| PubChem = 124087
| IUPHAR_ligand = 7157
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00967
| DrugBank = DB00967
Line 44: Line 70:
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1172
| 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)- 5''H''-benzo[5,6]cyclohepta[1,2-b]pyridine
| C=19 | H=19 | Cl=1 | N=2
| C = 19
| H = 19
| molecular_weight = 310.82
| Cl = 1
| N = 2
| smiles = Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
| smiles = Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
| InChI = 1/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
| InChIKey = JAUOIFJMECXRGI-UHFFFAOYAW
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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 = 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_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JAUOIFJMECXRGI-UHFFFAOYSA-N
| StdInChIKey = JAUOIFJMECXRGI-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}
'''Desloratadine''' is a drug used to treat [[allergy|allergies]]. It is marketed under several trade names such as '''NeoClarityn''', '''Claramax''', '''Clarinex''', '''Larinex''', '''Aerius''', '''Dazit''', '''Azomyr''' and '''Delot'''. It is an active [[metabolite]] of [[loratadine]], which is also on the market.


== Available forms ==
'''Desloratadine''', sold under the brand name '''Aerius''' among others, is a [[tricyclic]] [[Histamine H1 receptor|H1 receptor]] [[inverse agonist]] that is used to treat [[allergy|allergies]]. It is the major [[active metabolite]] of [[loratadine]].
Desloratadine is available as tablets (including orally disintegrating and extended release) and as syrup.FDA Electronic Orange Book http://www.fda.gov/cder/ob/default.htm.


== Mechanism of action ==
Desloratadine 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]].
Desloratadine is a tricyclic [[antihistamine]], which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. It has a long-lasting effect and in moderate and low doses, does not cause [[drowsiness]] because it does not readily enter the [[central nervous system]].{{cite journal | author=Mann R, Pearce G, 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=1184–6 | year=2000 | pmid=10784544 | url=http://bmj.bmjjournals.com/cgi/content/full/320/7243/1184 | doi=10.1136/bmj.320.7243.1184 | pmc=27362}}
== 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=Woźna J, Bałoniak A, Stępka J, Polańska A, Mojs E, Żaba R |title=Efficacy of Combined Oral Isotretinoin and Desloratadine or Levocetirizine vs. Isotretinoin Monotherapy in Treating Acne Vulgaris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |journal=Biomedicines |volume=13 |issue=8 |date=July 2025 |page=1847 |pmid=40868102 |pmc=12383536 |doi=10.3390/biomedicines13081847 |doi-access=free }}{{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 ==
== Side effects ==
The most common side effects are [[dry mouth]] (3%), [[fatigue (medical)|fatigue]] (1.2%), 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}}
Most common side-effects are [[fatigue (medical)|fatigue]], dry mouth, headache, and gastrointestinal disturbances.


== Interactions ==
== Desloratadine vs. loratadine ==
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}}
Desloratadine is the major metabolite of [[loratadine]]. There are no head-to-head randomised controlled trials of the two drugs. A survey of patients dissatisfied with loratadine published in August 2003 reported equal or better satisfaction with desloratadine,{{cite journal | author=Glass D, Harper A | title=Assessing satisfaction with desloratadine and fexofenadine in allergy patients who report dissatisfaction with loratadine | journal=BMC Fam Pract | date=August 13, 2003 | volume=4 | pages=10 | pmid=12917016 | doi=10.1186/1471-2296-4-10 | pmc=194638}} concluding:


== Pharmacology ==
When severity of disease was controlled for in the analysis, a pattern emerged suggesting greater levels of satisfaction amongst loratadine dissatisfied patients who converted to desloratadine. Point estimates suggest a consistent pattern favoring desloratadine patient satisfaction, with statistically significant results reported for sum of adverse effects, nighttime awakening due to symptoms, symptom severity just prior to the next dose, and overall satisfaction (''p'' < 0.05).
=== Pharmacodynamics ===
Desloratadine is a selective H1-[[antihistamine]] which functions as an [[inverse agonist]] at the [[HRH1|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 [[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.{{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}}
A November 2003 article published in the journal ''[[American Family Physician]]'' about the safety, tolerability, effectiveness, price, and simplicity of desloratadine concluded the following:{{cite journal | author=See S | title=Desloratadine for allergic rhinitis | journal=Am Fam Physician | volume=68 | issue=10 | pages=2015–6 | year=2003 | pmid=14655812 | url=http://www.aafp.org/afp/20031115/steps.html}}
Desloratadine is similar in effectiveness to [[fexofenadine]] and would be expected to produce results similar to loratadine and other nonsedating antihistamines. There is no clinical advantage to switching a patient from [[loratadine]] to desloratadine. However, it may be an option for patients whose [[Health insurance|medical insurance]] no longer covers loratadine if the co-pay is less than the cost of the [[Over-the-counter substance|over-the-counter product]].


=== Pharmacokinetics ===
In [[Canada]], desloratadine is available without a prescription, and as a generic. Prices are comparable to those of loratadine.
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.


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 [[biological half-life|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}}
==References==


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

Desloratadine 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]].

{{clear left}}

=== Pharmacogenomics ===
Two percent 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.

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

[[de:Desloratadin]]
[[es:Desloratadina]]
[[fr:Desloratadine]]
[[it:Desloratadina]]
[[nl:Desloratadine]]
[[pl:Desloratadyna]]
[[ru:Дезлоратадин]]
[[th:เดสลอราทาดีน]]
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