Desloratadine

Desloratadine

Clinical data
Trade names	Aerius, others [1]
Other names	Descarboethoxyloratadine [2]
AHFS/Drugs.com	Monograph
MedlinePlus	a602002
License data	US  DailyMed:  Desloratadine
Pregnancy category	AU:B1
Routes of administration	By mouth
Drug class	Second-generation antihistamine
ATC code	R06AX27 ( WHO )
Legal status
Legal status	AU: S2 (Pharmacy medicine) CA: OTC UK: POM (Prescription only) US: ℞-only [3] [4] EU:Rx-only/ OTC [5] [6] [7]
Pharmacokinetic data
Bioavailability	Rapidly absorbed
Protein binding	83–87%
Metabolism	UGT2B10, CYP2C8
Metabolites	3-Hydroxydesloratadine
Onset of action	within 1 hour
Elimination half-life	27 hours, 33.7 hours in elderly patients [3]
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  Y
PubChem CID	124087
IUPHAR/BPS	7157
DrugBank	DB00967  Y
ChemSpider	110575  Y
UNII	FVF865388R
KEGG	D03693  Y
ChEBI	CHEBI:291342  Y
ChEMBL	ChEMBL1172  Y
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 Y Key:JAUOIFJMECXRGI-UHFFFAOYSA-N Y
(verify)

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

It was patented in 1984 and came into medical use in 2001. ^[8] 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). ^[9] It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness. ^[9] Desloratadine is available in many dosage forms and under many brand names worldwide. ^[10]

An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy. ^{[11] [12]}

Side effects

The most common side effects are fatigue (1.2%), dry mouth (3%), and headache (0.6%). ^{[13] [9]}

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] [14]}

Pharmacology

Pharmacodynamics

Desloratadine is a selective H₁-antihistamine which functions as an inverse agonist at the histamine H₁ receptor. ^[15]

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. ^[16]

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. ^[14]

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. ^{[17] [18]} Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers. ^{[14] [19]}

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. ^[20]

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. ^[18]

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. ^{[14] [19]}

References

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. "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. "Desloratadine ratiopharm EPAR". European Medicines Agency (EMA). 13 January 2012. Retrieved 23 March 2025.
6. "Neoclarityn EPAR". European Medicines Agency (EMA). 15 January 2001. Retrieved 23 March 2025.
7. "Aerius EPAR". European Medicines Agency (EMA). 15 January 2001. Retrieved 24 March 2025.
8. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN   9783527607495.
9. 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.
10. "Desloratadine". Drugs.com. Retrieved 4 May 2015.
11. 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.
12. 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.
13. 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.
14. "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. Archived from the original (PDF) on 5 July 2019. Retrieved 21 January 2022.
15. 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.
16. "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 3 April 2006. Archived from the original (PDF) on 16 March 2018. Retrieved 13 October 2017.
17. 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.
18. 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.
19. "Desloratadine Monograph for Professionals". Drugs.com. 22 October 2024. Retrieved 24 March 2025.
20. 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.

Further reading

• Baena-Cagnani CE (2001). "Desloratadine activity in concurrent seasonal allergic rhinitis and asthma". Allergy. 56 Suppl 65: 21–7. doi:10.1111/j.1398-9995.2001.00001.x-i1. PMID   11243501.
• Devillier P, Roche N, Faisy C (2008). "Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review". Clinical Pharmacokinetics. 47 (4): 217–30. doi:10.2165/00003088-200847040-00001. PMID   18336052.
• Geha RS, Meltzer EO (April 2001). "Desloratadine: A new, nonsedating, oral antihistamine". The Journal of Allergy and Clinical Immunology. 107 (4): 751–62. doi:10.1067/mai.2001.114239. PMID   11295678.
• Henz BM (2001). "The pharmacologic profile of desloratadine: a review". Allergy. 56 Suppl 65: 7–13. doi:10.1034/j.1398-9995.2001.00101.x. PMID   11243504.