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Revision as of 14:08, 15 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit Latest revision as of 04:43, 15 November 2024 edit undoDrewx2 (talk | contribs)39 edits Unnecessary period removed.Tags: Mobile edit Mobile web edit 
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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''-benzocycloheptapyridine
{{Infobox drug
| verifiedrevid = 460777963
| image = Desloratadine.svg | image = Desloratadine.svg
| width = 222
| image2 = Desloratadine2.png
| alt =
| image2 = Desloratadine 3D ball-and-stick.png
| alt2 =


<!--Clinical data--> <!-- Clinical data -->
| tradename = Clarinex | pronounce =
| tradename = Clarinex, Aerius, Allex, 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}} | 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 = ]
| class =
| 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 = POM
| legal_UK_comment =
| legal_US = Rx-only | 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_status =
| legal_EU = Rx-only
| routes_of_administration = oral
| legal_EU_comment = <ref name="Allex EPAR">{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/allex|title=Allex EPAR |website=] (EMA) | date=19 May 2004 }}</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--> <!-- Pharmacokinetic data -->
| bioavailability = Rapidly absorbed | bioavailability = Rapidly absorbed
| protein_bound = 85% | protein_bound = 83 to 87%
| metabolism = Liver | metabolism = ], ]
| metabolites = 3-Hydroxydesloratadine
| elimination_half-life = 27 hours
| onset = within 1 hour<ref name="Lieberman_2008"/>
| excretion = 40% as conjugated metabolites into urine<br>Similar amount into the feces
| elimination_half-life = 27 hours,<ref name="Lieberman_2008"/> 33.7 hours in elderly patients<ref name="Clarinex FDA label" />
| duration_of_action = up to 24 hours<ref name="Lieberman_2008"/>
| excretion = 40% as conjugated metabolites into urine<br />Similar amount into the feces


<!--Identifiers--> <!-- Identifiers -->
| CASNo_Ref = {{cascite|correct|CAS}} | CAS_number_Ref = {{cascite|correct|??}}
| 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 74:
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1172 | 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 data--> <!-- Chemical and physical data -->
| IUPAC_name = 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5''H''-benzocycloheptapyridine
| C=19 | H=19 | Cl=1 | N=2
| C=19 | H=19 | Cl=1 | N=2
| molecular_weight = 310.82
| 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 ]. It is marketed under several trade names such as '''NeoClarityn''', '''Claramax''', '''Clarinex''', '''Larinex''', '''Aerius''', '''Dazit''', '''Azomyr''' and '''Delot'''. It is an active ] of ], which is also on the market.


<!-- Definition and medical uses -->
== Available forms ==
'''Desloratadine''' sold under the brand name '''Clarinex''' among others, is a ] ] that is used to treat ]. It is an ] of ].<ref name="Lieberman_2008">{{cite book | vauthors = Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ | title=Clinical Immunology | chapter=Antihistamines | publisher=Elsevier | year=2008 | doi=10.1016/b978-0-323-04404-2.10089-2 | pages=1317–1329 | isbn=9780323044042 }}</ref>
Desloratadine is available as tablets (including orally disintegrating and extended release) and as syrup.<ref>FDA Electronic Orange Book http://www.fda.gov/cder/ob/default.htm.</ref>


<!-- Society and culture -->
== Mechanism of action ==
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 ].<ref name="Clarinex FDA label" />
Desloratadine is a tricyclic ], which has a selective and peripheral H<sub>1</sub>-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 ] because it does not readily enter the ].<!--

--><ref>{{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}}</ref>
== Medical uses ==
Desloratadine is used to treat ], ] and ] (]).<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 ] of ] 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 ], as an inexpensive adjuvant to ] 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 == == Side effects ==
The most common side-effects are ] (1.2%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453"/>), ] (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 ] (0.6%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453"/>).<ref name=AFP2003/>
Most common side-effects are ], dry mouth, headache, and gastrointestinal disturbances.


== Interactions ==
== Desloratadine vs. loratadine ==
Co-administration with ], ], ], ], or ] resulted in elevated blood plasma concentrations of desloratadine and its ] 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=]|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>
Desloratadine is the major metabolite of ]. 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<!--
-->,<ref>{{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}}</ref> concluding:


== Pharmacology ==
<blockquote>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).</blockquote>
=== Pharmacodynamics ===
Desloratadine is a selective H<sub>1</sub>-] which functions as an ] at the ].<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 ] at various subtypes of the ]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=]|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>
A November 2003 article published in the journal '']'' about the safety, tolerability, effectiveness, price, and simplicity of desloratadine concluded the following:<!--
--><ref>{{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}}</ref>
<blockquote>Desloratadine is similar in effectiveness to ] and would be expected to produce results similar to loratadine and other nonsedating antihistamines. There is no clinical advantage to switching a patient from ] to desloratadine. However, it may be an option for patients whose ] no longer covers loratadine if the co-pay is less than the cost of the ].</blockquote>


=== Pharmacokinetics ===
In ], 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 ] concentrations after about three hours. In the bloodstream, 83 to 87% of the substance are bound to ]s.<ref name="EPAR" />


Desloratadine is metabolized to 3-hydroxydesloratadine in a three-step sequence in normal metabolizers. First, N-glucuronidation of desloratadine by ]; then, 3-hydroxylation of desloratadine N-glucuronide by ]; 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 ] of 27 hours in normal metabolizers.<ref name="EPAR" /><ref name="Drugs.com">]: Desloratadine {{Drugs.com|monograph|desloratadine}}.</ref>
==References==
<references />


].]]

It exhibits only peripheral activity since it does not readily cross the ]; hence, it does not normally cause ] because it does not readily enter the ].<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 ] system. It was found to weakly inhibit ], ], and ]/], and not to inhibit ], ], ], or ]. Desloratadine was found to be a potent and relatively selective inhibitor of ], a weak to moderate inhibitor of ], ], and ], and not to inhibit ], ], ], ], ], ], ], ], and ].<ref name="further characterization" />

{{clear left}}

=== Pharmacogenomics ===
2% of ] and 18% of people from African descent are desloratadine ]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}}

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


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