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{{short description|Allergy medication}}
{{Short description|Allergy medication}}
{{Use dmy dates|date=May 2024}}
{{Drugbox
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| verifiedrevid = 460777963
| verifiedrevid = 460777963
⚫
| IUPAC_name = 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5''H''-benzo[5,6]cyclohepta[1,2-b]pyridine
| image = Desloratadine.svg
| image = Desloratadine.svg
| width = 222
| width = 222
| alt =
| image2 = Desloratadine 3D ball-and-stick.png
| image2 = Desloratadine 3D ball-and-stick.png
| alt2 =


<!--Clinical data-->
<!-- Clinical data -->
| pronounce =
| tradename = Clarinex, Aerius, Allex, others<ref name="murdoch">{{Cite journal|title=Desloratadine: an update of its efficacy in the management of allergic disorders|first1=David|last1=Murdoch|first2=Karen L.|last2=Goa|first3=Susan J.|last3=Keam|date=April 7, 2003|journal=Drugs|volume=63|issue=19|pages=2051–2077|doi=10.2165/00003495-200363190-00010|pmid=12962522}}</ref><ref name="Allex EPAR">{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/allex|title=Allex EPAR |website=[[European Medicines Agency]] (EMA) }}</ref>
| 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
| licence_EU = yes
| DailyMedID = Desloratadine
| DailyMedID = Desloratadine
| 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 =
| ATC_prefix = R06
⚫
| ATC_suffix = AX27
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S2
| 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 = 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_EU = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Allex EPAR">{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/allex|title=Allex EPAR |website=[[European Medicines Agency]] (EMA) | date=19 May 2004 }}</ref>
| legal_status =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
⚫
| routes_of_administration = [[Oral administration|By mouth]] (tablets, solution)
| ATC_prefix = R06
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->
⚫
| ATC_suffix = AX27


<!--Pharmacokinetic data-->
<!-- Pharmacokinetic data -->
| bioavailability = Rapidly absorbed
| bioavailability = Rapidly absorbed
| protein_bound = 83 to 87%
| protein_bound = 83 to 87%
| onset = within 1 hour <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| metabolism = [[UGT2B10]], [[CYP2C8]]
| metabolism = [[UGT2B10]], [[CYP2C8]]
| metabolites = 3-Hydroxydesloratadine
| metabolites = 3-Hydroxydesloratadine
| onset = within 1 hour<ref name="Lieberman_2008"/>
⚫
| duration_of_action = up to 24 hours <ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| elimination_half-life = 27 hours<ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329"/>
| 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
| excretion = 40% as conjugated metabolites into urine<br />Similar amount into the feces


<!--Identifiers-->
<!-- Identifiers -->
⚫
| IUPHAR_ligand = 7157
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 100643-71-8
| CAS_number = 100643-71-8
| CAS_supplemental =
| PubChem = 124087
| PubChem = 124087
⚫
| IUPHAR_ligand = 7157
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00967
| DrugBank = DB00967
Line 54: 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''-benzo[5,6]cyclohepta[1,2-b]pyridine
| C=19 | H=19 | Cl=1 | N=2
| C=19 | H=19 | Cl=1 | N=2
| smiles = Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
| smiles = Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
| 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 =
}}
}}

<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Desloratadine''' (trade names '''Clarinex''' and '''Aerius''') 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]].<ref name="Lieberman Hernandez-Trujillo Lieberman Frew 2008 pp. 1317–1329">{{cite book | last=Lieberman | first=Phil | last2=Hernandez-Trujillo | first2=Vivian | last3=Lieberman | first3=Jay | last4=Frew | first4=Anthony J. | title=Clinical Immunology | chapter=Antihistamines | publisher=Elsevier | year=2008 | doi=10.1016/b978-0-323-04404-2.10089-2 | pages=1317–1329 | quote=Desloratadine is a metabolite of loratadine. The onset of action is within 1 hour. Peak serum concentrations of desloratadine appear 3 hours after dosing. The mean elimination half-life of desloratadine is 27 hours and that of its metabolite is 36 hours. The consumption of food does not interfere with the absorption of desloratadine. Wheal inhibition is detected 1 hour after administration and may last 24 hours. }}</ref>
'''Desloratadine'''. sold under the brand name '''Clarinex''' 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]].<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>


<!-- Society and culture -->
<!-- Society and culture -->
It was patented in 1984 and came into medical use in 2001.<ref name=Fis2006>{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |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 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 ==
== Medical uses ==
Desloratadine is used to treat [[allergic rhinitis]], [[nasal congestion]] and chronic idiopathic urticaria ([[hives]]).<ref name=AFP2003>{{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> 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 trade names worldwide.<ref>Drugs.com [https://www.drugs.com/international/desloratadine.html Desloratadine entry at drugs.com international] Page accessed May 4, 2015</ref>
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=J Eur Acad Dermatol Venereol | volume=28 | issue=12 | pages=1654–60 | year=2014 | pmid=25081735 | doi=10.1111/jdv.12403| s2cid=3406128 }}</ref><ref name=DC2016>{{cite journal | author=Layton AM | title=Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris | journal=Dermatol Clin | volume=34 | issue=2 | pages=147–57 | year=2016 | pmid=27015774 | doi=10.1016/j.det.2015.11.008}}</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 ==
== 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 | last1=González-Núñez | first1=Vanesa | last2=Valero | first2=Antonio | last3=Mullol | first3=Joaquim | title=Safety evaluation of desloratadine in allergic rhinitis | journal=Expert Opinion on Drug Safety | publisher=Informa Healthcare | volume=12 | issue=3 | date=2013-04-11 | issn=1474-0338 | pmid=23574541 | doi=10.1517/14740338.2013.788148 | pages=445–453| s2cid=40472187 }}</ref>), and [[headache]] (0.6%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453"/>).<ref name=AFP2003/>
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 ==
== 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>{{cite web |title=Clarinex: Prescribing Information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021165s017,021300s014,021312s015,021563s003lbl.pdf |publisher=[[U.S. Food and Drug Administration]] |access-date=2022-01-21}}</ref><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=2022-01-21}}</ref>
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 ==
== Pharmacology ==
=== Pharmacodynamics ===
=== 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 = World Allergy Organ J | volume = 4 | issue = 2 | pages = 47–53 | year = 2011 | pmid = 23268457 | pmc = 3500039 | doi = 10.1097/WOX.0b013e3182093e19 }}</ref>
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=2006-04-03}}</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 ===
=== 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 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="further characterization">{{cite journal | last1=Kazmi | first1=F. | last2=Yerino | first2=P. | last3=Barbara | first3=J. E. | last4=Parkinson | first4=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 | date=2015-07-01 | issn=1521-009X | doi=10.1124/dmd.115.065011 | pmid=26135009 | pages=1294–1302| 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">[[Drugs.com]]: Desloratadine {{Drugs.com|monograph|desloratadine}}.</ref>
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">[[Drugs.com]]: Desloratadine {{Drugs.com|monograph|desloratadine}}.</ref>


[[File:3-Hydroxydesloratadine skeletal.svg|thumb|left|3-Hydroxydesloratadine is the main [[metabolite]].]]
[[File:3-Hydroxydesloratadine skeletal.svg|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 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>
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" />
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" />
Line 100: Line 136:


=== Pharmacogenomics ===
=== Pharmacogenomics ===
2% of [[Caucasian race|Caucasian people]] and 18% of people from African descent are desloratadine [[poor metabolizer]]s. In these people, the drug reaches threefold highest plasma concentrations six to seven hours after intake, and has a half-life of about 89 hours. However, the safety profile for these subjects is not worse than for extensive (normal) metabolizers.<ref name="EPAR" /><ref name="Drugs.com" />
2% of [[Caucasian race|Caucasian people]] 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" />


== See also ==
== References ==
* [[Benzocycloheptenes]]
* [[Azatadine]]

==References==
{{Reflist}}
{{Reflist}}


== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/desloratadine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Desloratadine }}

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{{Schering-Plough}}
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{{Antihistamines}}
{{Histaminergics}}
{{Histaminergics}}
{{Tricyclics}}
{{Tricyclics}}
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{{Schering-Plough}}
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[[Category:Peripherally selective drugs]]
[[Category:Piperidines]]
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[[Category:Drugs developed by Schering-Plough]]
[[Category:Merck & Co. brands]]
[[Category:Drugs developed by Merck & Co.]]

Latest revision as of 04:17, 1 June 2024

Desloratadine
Clinical data
Trade namesClarinex, Aerius, Allex, others[1]
Other namesdescarboethoxyloratadine[2]
AHFS/Drugs.comMonograph
MedlinePlusa602002
License data
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityRapidly absorbed
Protein binding83 to 87%
MetabolismUGT2B10, CYP2C8
Metabolites3-Hydroxydesloratadine
Onset of actionwithin 1 hour[6]
Elimination half-life27 hours,[6] 33.7 hours in elderly patients[3]
Duration of actionup to 24 hours[6]
Excretion40% as conjugated metabolites into urine
Similar amount into the feces
Identifiers
  • 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5H-benzo[5,6]cyclohepta[1,2-b]pyridine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.166.554 Edit this at Wikidata
Chemical and physical data
FormulaC19H19ClN2
Molar mass310.83 g·mol−1
3D model (JSmol)
  • Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
  • InChI=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 checkY
  • Key:JAUOIFJMECXRGI-UHFFFAOYSA-N checkY
  (verify)

Desloratadine. sold under the brand name Clarinex among others, is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine.[6]

It was patented in 1984 and came into medical use in 2001.[7] It was brought to the market in the US by Schering Corporation, later named Schering-Plough.[3]

Medical uses

[edit]

Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives).[8] It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness.[8] Desloratadine is available in many dosage forms and under many brand names worldwide.[9]

An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.[10][11]

Side effects

[edit]

The most common side-effects are fatigue (1.2%[12]), dry mouth (3%[12]), and headache (0.6%[12]).[8]

Interactions

[edit]

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.[3][13]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Desloratadine is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor.[14]

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.[15]

Pharmacokinetics

[edit]

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.[13]

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.[16][17] Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.[13][18]

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.[19]

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.[17]

Pharmacogenomics

[edit]

2% of Caucasian people 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.[13][18]

References

[edit]
  1. ^ Murdoch D, Goa KL, Keam SJ (7 April 2003). "Desloratadine: an update of its efficacy in the management of allergic disorders". Drugs. 63 (19): 2051–2077. doi:10.2165/00003495-200363190-00010. PMID 12962522. S2CID 195689362.
  2. ^ Schering Corporation (2000). "CLARITIN brand of Loratadine - Full Prescribing Information (US FDA)" (PDF). US FDA. Retrieved 17 May 2024. loratadine is metabolized to descarboethoxyloratadine predominantly by cytochrome P450 3A4 (CYP3A4) and, to a lesser extent, by cytochrome P450 2D6 (CYP2D6).
  3. ^ a b c d "Clarinex- desloratadine tablet, film coated". DailyMed. 14 November 2022. Retrieved 18 May 2024.
  4. ^ "Clarinex-D 12 HOUR- desloratadine and pseudoephedrine sulfate tablet, extended release". DailyMed. 14 November 2022. Retrieved 18 May 2024.
  5. ^ "Allex EPAR". European Medicines Agency (EMA). 19 May 2004.
  6. ^ a b c d Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ (2008). "Antihistamines". Clinical Immunology. Elsevier. pp. 1317–1329. doi:10.1016/b978-0-323-04404-2.10089-2. ISBN 9780323044042.
  7. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN 9783527607495.
  8. ^ a b c See S (November 2003). "Desloratadine for allergic rhinitis". American Family Physician. 68 (10): 2015–2016. PMID 14655812. Archived from the original on 24 July 2005. Retrieved 1 August 2005.
  9. ^ "Desloratadine". Drugs.com. Retrieved 4 May 2015.
  10. ^ Lee HE, Chang IK, Lee Y, Kim CD, Seo YJ, Lee JH, et al. (December 2014). "Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study". Journal of the European Academy of Dermatology and Venereology. 28 (12): 1654–1660. doi:10.1111/jdv.12403. PMID 25081735. S2CID 3406128.
  11. ^ Layton AM (April 2016). "Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris". Dermatologic Clinics. 34 (2): 147–157. doi:10.1016/j.det.2015.11.008. PMID 27015774.
  12. ^ a b c González-Núñez V, Valero A, Mullol J (May 2013). "Safety evaluation of desloratadine in allergic rhinitis". Expert Opinion on Drug Safety. 12 (3). Informa Healthcare: 445–453. doi:10.1517/14740338.2013.788148. PMID 23574541. S2CID 40472187.
  13. ^ a b c d "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. Archived from the original (PDF) on 5 July 2019. Retrieved 21 January 2022.
  14. ^ Canonica GW, Blaiss M (February 2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". The World Allergy Organization Journal. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC 3500039. PMID 23268457.
  15. ^ "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 3 April 2006. Archived from the original (PDF) on 16 March 2018. Retrieved 13 October 2017.
  16. ^ Kazmi F, Barbara JE, Yerino P, Parkinson A (April 2015). "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". Drug Metabolism and Disposition. 43 (4): 523–533. doi:10.1124/dmd.114.062620. PMID 25595597.
  17. ^ a b Kazmi F, Yerino P, Barbara JE, Parkinson A (September 2015). "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". Drug Metabolism and Disposition. 43 (9): 1294–1302. doi:10.1124/dmd.115.065011. PMID 26135009.
  18. ^ a b Drugs.com: Desloratadine Monograph.
  19. ^ Mann RD, Pearce GL, Dunn N, Shakir S (April 2000). "Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice". BMJ. 320 (7243): 1184–1186. doi:10.1136/bmj.320.7243.1184. PMC 27362. PMID 10784544.
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