Desloratadine: A new, nonsedating, oral antihistamine

doi:10.1067/mai.2001.114239

Journal of Allergy and Clinical Immunology

Volume 107, Issue 4, April 2001, Pages 751-762

https://doi.org/10.1067/mai.2001.114239 Get rights and content

Abstract

Desloratadine is a new, selective, H₁-receptor antagonist that also has anti-inflammatory activity. In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD₂, leukotriene C₄, tryptase, histamine, and the TNF-α–induced chemokine RANTES. Desloratadine also inhibits the induction of cell adhesion molecules, plateletactivating factor–induced eosinophil chemotaxis, TNF-α–induced eosinophil adhesion, and spontaneous and phorbol myristate acetate–induced superoxide generation in vitro. In animals desloratadine had no effect on the central nervous, cardiovascular, renal, or gastrointestinal systems. Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and has a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject’s age, race, or sex. There are no clinically relevant interactions between desloratadine and erythromycin, ketoconazole, or grapefruit juice. Desloratadine is not a significant substrate of the P-glycoprotein transport system. Once daily administration of desloratadine rapidly reduces the nasal and nonnasal symptoms of seasonal allergic rhinitis, including congestion. In patients with seasonal allergic rhinitis and concomitant asthma, desloratadine treatment was also associated with significant reductions in total asthma symptom score and use of inhaled β₂-agonists. Use of desloratadine in patients with chronic idiopathic urticaria was associated with significant reductions in pruritus, number of hives, size of the largest hive, and interference with sleep and daily activities. Clinical experience in over 2300 patients has shown that the adverse event profile of desloratadine is similar to that of placebo; desloratadine has no clinically relevant effects on electrocardiographic parameters, does not impair wakefulness or psychomotor performance, and does not exacerbate the psychomotor impairment associated with alcohol use. (J Allergy Clin Immunol 2001;107:751-62.)

Section snippets

Rationale for drug development

Allergic rhinitis is a common disease that affects up to 50 million Americans and up to 30% of the population in Europe.1, 2 With the prevalence of the disease increasing, even greater numbers of the population will be affected in the future. Appropriate treatment is important to alleviate the signs and symptoms of allergic rhinitis, including sneezing, rhinorrhea, nasal congestion/stuffiness, and nasal pruritus, to improve patients’ quality of life, and to facilitate the management of

Antihistaminic activity

Desloratadine is an orally active H₁-receptor antagonist. In radioligand-receptor binding assays performed with isolated H₁ receptors from guinea pig lung and brain, desloratadine was 15 times more potent than loratadine and 10 to 20 times more potent than terfenadine in displacing tritiated mepyramine. Desloratadine was also 18 times more potent than loratadine in inhibiting tritiated pyrilamine binding to H₁ receptors isolated from rat brain. Functionally, desloratadine was approximately 10

Clinical pharmacokinetics

The pharmacokinetic properties of desloratadine have been studied in single- and multiple-dose trials, which demonstrated that desloratadine is rapidly absorbed and has a long half-life of approximately 27 hours. With daily administration of 5 mg of desloratadine, steady-state serum concentrations are achieved within 7 days. The steady-state pharmacokinetic parameters of desloratadine and its main metabolite, 3-OH desloratadine, are provided in Table II.

. Steady-state pharmacokinetic values of

Efficacy in patients with seasonal allergic rhinitis

Multiple studies have demonstrated the efficacy of desloratadine in the treatment of seasonal allergic rhinitis (SAR). One set of efficacy evaluations was used consistently in all of the studies. Twice daily (once in the morning, immediately before study drug administration, and once in the evening, approximately 12 hours later), patients assessed nasal symptoms (rhinorrhea, nasal congestion/stuffiness, nasal itching, and sneezing) and nonnasal symptoms (itching/burning eyes, tearing/watering

Efficacy in patients with nasal congestion

Several studies have shown that therapy with once daily desloratadine significantly improves nasal congestion.³³ Relief of nasal congestion was examined in 3 multicenter, double-blind, placebo-controlled studies involving 278 to 346 patients with clinically symptomatic SAR. The endpoint for assessment of nasal congestion/stuffiness was the mean change from baseline in the morning/evening reflective congestion score averaged over the duration of the study, either 2 or 4 weeks. Baseline values in

Efficacy in patients with concomitant seasonal allergic rhinitis and asthma

Allergic rhinitis has been associated with asthma: up to 58% of patients with allergic rhinitis also have asthma.³⁴ A number of studies have demonstrated that appropriate management of allergic rhinitis in patients with asthma also results in improvement of asthma symptoms, decreased bronchial sensitivity, protection against bronchospasm, and decreased use of asthma rescue medications.3, 4, 34, 35 Furthermore, it has been suggested that optimal control of asthma may require effective control of

Efficacy in patients with chronic idiopathic urticaria

Desloratadine has also been evaluated for the treatment of chronic idiopathic urticaria (CIU), another common condition in which antihistamines are first-line agents. In a multicenter, randomized, double-blind study, 190 patients 12 years of age or older with at least a 6-week history of CIU and who were experiencing a flare of at least moderate severity were randomized to treatment with 5 mg of desloratadine once daily or placebo for 6 weeks. Twice daily, patients evaluated the severity of CIU

Adverse effects

The overall adverse event profile for desloratadine is similar to that of placebo, as shown in 2 large studies conducted during the spring and fall allergy seasons (Table III).³²

. Incidence of treatment-emergent adverse events reported by 5% or more of the subjects in any treatment group by body system/organ class (all randomized subjects)^*

	Fall study		Spring study
Empty Cell	No.^† (%) of subjects
	Desloratadine, 5 mg (n = 164)	Placebo (n = 164)	Desloratadine, 5 mg (n = 172)	Placebo (n = 174)
No. of subjects (%) with

Dosage and administration

Various clinical studies have demonstrated that the long half-life of desloratadine allows once daily dosing. A 5-mg once daily dose is appropriate for treatment of both SAR and CIU. Because the pharmacokinetic parameters of desloratadine are not altered by subject race, sex, or age, no dosage adjustments are required on the basis of these factors for patients 12 years of age or older. Dosage adjustment is also not required if desloratadine is administered concomitantly with ketoconazole,

Summary

Allergic rhinitis is a common disease that is associated with substantial morbidity. Although there are many treatments available for the disease, none are ideal. There continues to be a need for treatments that relieve all of the signs and symptoms of the disease, do not cause adverse effects, do not have drug or food interactions, and can be conveniently administered.

Desloratadine is a new antihistamine that binds with higher affinity to the H₁ receptor than most other H₁-receptor

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To evaluate and review sex effects in the pharmacokinetics and /-dynamics of drugs used to treat itch.
In this narrative review we performed a PubMed and MEDLINE (Ovid) search using the terms (itch OR pruritus) AND (gender OR sex) AND (drug OR medication OR pharmacokinetics OR pharmacodynamics). Additional searches were performed for the topical and systemic drugs recommended by the European Guideline on Chronic Pruritus.
We found numerous reports with variable levels of evidence of sex effects with respect to the pharmacokinetics and/or pharmacodynamics of 14 drug classes used for the treatment of itch, including a total of 19 systemic and 3 topical drugs. Women seem to present higher plasma levels of several drugs used in itch treatment, including tri- and tetracyclic antidepressants (e.g. doxepin, amitriptyline, mirtazapine), serotonin reuptake inhibitors (e.g. paroxetine, sertraline, fluoxetine), immunosuppressive drugs (e.g. cyclosporine, mycophenolate mofetil), serotonin receptor antagonists (e.g. ondansetron) and betablockers (e.g. propranolol). Adverse drug reactions (ADRs) were generally more common in women. Being female was reported to be an independent risk factor for QTc-prolongation associated with antihistamines and tetracyclic antidepressants. Additionally, women seem to be more prone to sedative effects of antihistamines, and to suffer from a higher frequency as well as severity of side effects with systemic calcineurin inhibitors, opioid agonists, and opioid antagonists. Women were also sensitised more often to topically applied drugs. Of note, apart from only one experimental study with capsaicin, none of these reports were designed specifically to assess the effect of sex (and gender) in the treatment of itch.
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Efficacy and safety of rupatadine in Japanese patients with seasonal allergic rhinitis: A double-blind, randomized, multicenter, placebo-controlled clinical trial
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Furthermore, desloratadine and its hydroxylated metabolites are some of the rupatadine metabolites that contribute to the drug's overall efficacy.12 In fact, desloratadine is an antihistamine with a long half-life of 27 h.13 These facts suggest rapid onset and extended duration of efficacy. The efficacy and safety of rupatadine have been established in overseas populations.8,14
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The study showed desloratadine in dose 7.5 mg not to increase sedation or impaired psychomotor performance. Geha et al. [70] and Scharf et al. [68,69] concluded that desloratadine does not increase CNS impairment caused by alcohol. Interaction between ebastine and alcohol was evaluated by Mattila et al. [71].
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A systematic literature queries were performed in the following databases: Medline (via PubMed), Cochrane Library, Embase and Web of Science (all from their inception date till October 2016). The queries covered nine specific names of second generation anthistamine drugs, namely bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine, in combinations with such terms as “food”, “juice”, “grapefruit”, “fruits”, “alcohol”, “pharmacokinetics”, and “meal”. Additional publications were found by checking all the reference lists. Where none data on drug-food interaction could be found within the investigated databases, a specific drug prescribing information was used. 2326 publications were identified with the database queries. Articles were subjected to analysis by reviewing their title, abstract and full text; duplicated papers were removed. Having collected a complete set of data, a critical review was undertaken.
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^☆: Series editors: Donald Y. M. Leung, MD, PhD, Harold S. Nelson, MD, Stanley J. Szefler, MD, Philip S. Norman, MD, and Andrea Apter, MD, MSc

^☆☆: Reprint requests: Raif S. Geha, MD, Boston Children’s Hospital, Enders Building, Room 809, 300 Longwood Ave, Boston, MA 02115.

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New ProductsDesloratadine: A new, nonsedating, oral antihistamine☆,☆☆

Abstract

Section snippets

Rationale for drug development

Antihistaminic activity

Clinical pharmacokinetics

Efficacy in patients with seasonal allergic rhinitis

Efficacy in patients with nasal congestion

Efficacy in patients with concomitant seasonal allergic rhinitis and asthma

Efficacy in patients with chronic idiopathic urticaria

Adverse effects

Dosage and administration

Summary

Ann Allergy Asthma Immunol

Clin Ther

Ann Allergy Asthma Immunol

Epidemiology of rhinitis and asthma

Clin Exp Allergy

Allergic rhinitis: epidemiology and natural history

Allergy Asthma Proc

Consensus statement on the treatment of allergic rhinitis

Allergy

Sedation with “non-sedating” antihistamines: four prescription-event monitoring studies in general practice

BMJ

Pharmacokinetic overview of oral second-generation H1 antihistamines

Int J Clin Pharmacol Ther

OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine

Drug Metab Dispos

Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H1 receptor antagonist: 1st communication: receptor selectivity, antihistaminic activity, and antiallergenic effects

Arzneimittelforschung

Functional characterization of desloratadine and other antihistamines in human histamine H1 receptors

Allergy

Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRI+ cells

Clin Exp Allergy

Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist descarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines

Exp Dermatol

Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells

Allergy

Desloratadine attenuation of eosinophil chemotaxis, adhesion, and superoxide generation

Allergy

Evaluation of the CNS properties of SCH 29851, a potential non-sedating antihistamine

Agents Actions

New Products
Desloratadine: A new, nonsedating, oral antihistamine☆,☆☆

Functional characterization of desloratadine and other antihistamines in human histamine H₁ receptors

Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRI⁺ cells