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Desloratadine
Clinical data
Trade names	Clarinex, Aerius, Allex, others
Other names	descarboethoxyloratadine
AHFS/Drugs.com	Monograph
MedlinePlus	a602002
License data	US DailyMed: Desloratadine;
Pregnancy; category	AU: B1; ;
Routes of; administration	By mouth
ATC code	R06AX27 (WHO) ;
Legal status
Legal status	AU: S2 (Pharmacy medicine); CA: OTC; UK: POM (Prescription only); US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	Rapidly absorbed
Protein binding	83 to 87%
Metabolism	UGT2B10, CYP2C8
Metabolites	3-Hydroxydesloratadine
Onset of action	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
Identifiers
	IUPAC name 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5H-benzo[5,6]cyclohepta[1,2-b]pyridine;
CAS Number	100643-71-8 ;
PubChem CID	124087;
IUPHAR/BPS	7157;
DrugBank	DB00967 ;
ChemSpider	110575 ;
UNII	FVF865388R;
KEGG	D03693 ;
ChEBI	CHEBI:291342 ;
ChEMBL	ChEMBL1172 ;
CompTox Dashboard (EPA)	DTXSID1044196 ;
ECHA InfoCard	100.166.554
Chemical and physical data
Formula	C19H19ClN2
Molar mass	310.83 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4;
	InChI 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 ; Key:JAUOIFJMECXRGI-UHFFFAOYSA-N ;
	(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

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

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

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.^[3]^[13]

Pharmacology

Pharmacodynamics

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

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]

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

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

^ 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.
^ 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).
^ ^a ^b ^c ^d "Clarinex- desloratadine tablet, film coated". DailyMed. 14 November 2022. Retrieved 18 May 2024.
^ "Clarinex-D 12 HOUR- desloratadine and pseudoephedrine sulfate tablet, extended release". DailyMed. 14 November 2022. Retrieved 18 May 2024.
^ "Allex EPAR". European Medicines Agency (EMA). 19 May 2004.
^ ^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.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN 9783527607495.
^ ^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.
^ "Desloratadine". Drugs.com. Retrieved 4 May 2015.
^ 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.
^ 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.
^ ^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.
^ ^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.
^ 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.
^ "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 3 April 2006. Archived from the original (PDF) on 16 March 2018. Retrieved 13 October 2017.
^ 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.
^ ^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.
^ ^a ^b Drugs.com: Desloratadine Monograph.
^ 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.

[murdoch-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.

[loratadine-fda-2000-2] 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).

[Clarinex_FDA_label-3] "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.

[Allex_EPAR-5] "Allex EPAR". European Medicines Agency (EMA). 19 May 2004.

[Lieberman_2008-6] 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.

[Fis2006-7] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN 9783527607495.

[AFP2003-8] 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.

[JEADV2014-10] 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.

[DC2016-11] 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.

[González-Núñez_Valero_Mullol_2013_pp._445–453-12] 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.

[EPAR-13] "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. Archived from the original (PDF) on 5 July 2019. Retrieved 21 January 2022.

[Desloratedine-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.

[kazmi-april-2015-16] 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.

[further_characterization-17] 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.

[Drugs.com-18] 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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PROFILPELAJAR.COM

Desloratadine

Medical uses

Side effects

Interactions

Pharmacology

Pharmacodynamics

Pharmacokinetics

Pharmacogenomics

References

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