Desloratadine

Desloratadine (trade name Clarinex and Aerius) is a tricyclic H1 antagonist that is used to treat allergies. It is an active metabolite of loratadine.

Desloratadine
Clinical data
Trade namesClarinex (US), Aerius, Dasselta, Deslordis (EU), Allex[1][2] and others
AHFS/Drugs.comMonograph
MedlinePlusa602002
License data
Pregnancy
category
  • AU: B1
  • US: C (Risk not ruled out)
    Routes of
    administration    		Oral (tablets, solution)
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    BioavailabilityRapidly absorbed
    Protein binding83 to 87%
    MetabolismUGT2B10, CYP2C8
    Metabolites3-Hydroxydesloratadine
    Onset of actionwithin 1 hour
    Elimination half-life27 hours
    Duration of actionup to 24 hours
    Excretion40% as conjugated metabolites into urine
    Similar amount into the feces
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.166.554
    Chemical and physical data
    FormulaC19H19ClN2
    Molar mass310.83 g·mol−1
    3D model (JSmol)
      (verify)

    It was patented in 1984 and came into medical use in 2001.[3]

    Medical uses

    Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives).[4] It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness.[4] Desloratadine is available in many dosage forms and under many trade names worldwide.[5]

    An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.[6][7]

    Side effects

    The most common side-effects are fatigue, dry mouth, and headache.[4]

    Interactions

    A number of drugs and other substances that are prone to interactions, such as ketoconazole, erythromycin and grapefruit juice, have shown no influence on desloratadine concentrations in the body. Desloratadine is judged to have a low potential for interactions.[8]

    Pharmacology

    Pharmacodynamics

    Desloratadine is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor.[9]

    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.[10]

    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.[8]

    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.[11] Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.[8][12]

    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.[13]

    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.[11]

    Pharmacogenomics

    2% of Caucasian people and 18% of people from African descent are desloratadine poor metabolizers. 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.[8][12]

    Price

    When initially released in Canada in 2002 it sold for CA$0.82 per dose.[14]

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    See also

    References
    1. Murdoch, David; Goa, Karen L.; Keam, Susan J. (April 7, 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.
    2. "Allex". European Medicines Agency. September 17, 2018.
    3. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN 9783527607495.
    4. See S (2003). "Desloratadine for allergic rhinitis". Am Fam Physician. 68 (10): 2015–6. PMID 14655812.
    5. Drugs.com Desloratadine entry at drugs.com international Page accessed May 4, 2015
    6. Lee HE, Chang IK, Lee Y, Kim CD, Seo YJ, Lee JH, Im M (2014). "Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study". J Eur Acad Dermatol Venereol. 28 (12): 1654–60. doi:10.1111/jdv.12403. PMID 25081735.
    7. Layton AM (2016). "Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris". Dermatol Clin. 34 (2): 147–57. doi:10.1016/j.det.2015.11.008. PMID 27015774.
    8. "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. 2017-06-07.
    9. Canonica GW, Blaiss M (2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". World Allergy Organ J. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC 3500039. PMID 23268457.
    10. "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 2006-04-03.
    11. Kazmi, F.; Yerino, P.; Barbara, J. E.; Parkinson, A. (2015-07-01). "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. ISSN 1521-009X. PMID 26135009.
    12. Drugs.com: Desloratadine Monograph.
    13. Mann R, Pearce G, Dunn N, Shakir S (2000). "Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice". BMJ. 320 (7243): 1184–6. doi:10.1136/bmj.320.7243.1184. PMC 27362. PMID 10784544.
    14. "Report on New Patented Drugs - Aerius". pmprb-cepmb.gc.ca. 13 May 2014. Retrieved 25 November 2019.
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