Desloratadine

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

It was patented in 1984 and came into medical use in 2001.<ref name=Fis2006>Template:Cite book</ref> It was brought to the market in the US by Schering Corporation, later named Schering-Plough.<ref name="Clarinex FDA label" />

Medical uses

Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives).<ref name=AFP2003>Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite journal</ref><ref name=DC2016>Template:Cite journal</ref>

Side effects

The most common side-effects are 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">Template:Cite journal</ref>), and headache (0.6%<ref name="González-Núñez Valero Mullol 2013 pp. 445–453"/>).<ref name=AFP2003/>

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 name="Clarinex FDA label" /><ref name="EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Pharmacology

Pharmacodynamics

Desloratadine is a selective H₁-antihistamine which functions as an inverse agonist at the histamine H₁ receptor.<ref name="Desloratedine">Template:Cite journal</ref>

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<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="kazmi-april-2015">Template:Cite journal</ref><ref name="further characterization">Template:Cite journal</ref> Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.<ref name="EPAR" /><ref name="Drugs.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

File:3-Hydroxydesloratadine skeletal.svg

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>Template:Cite journal</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" />

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.<ref name="EPAR" /><ref name="Drugs.com" />

Further reading

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