Desloratadine

A second-generation tricyclic antihistamine called desloratadine is used for the management of seasonal and perennial allergic rhinitis, and urticaria.  Desloratadine is the active descarboethoxy metabolite of loratadine and has a selective and peripheral H1-antagonist action. It exhibits a long-lasting effect and does not elicit drowsiness since it does not readily enter the central nervous system.

Pharmacological Class: Tricyclic antihistamine [1]  

It is indicated to treat chronic idiopathic urticaria, perennial allergic rhinitis, and seasonal allergic rhinitis. [2]

Desloratadine interacts with free histamines like other H1-blockers for binding to H1-receptors in the bronchial smooth muscle, large blood vessels, uterus, and gastrointestinal tract. This prevents endogenous histamine from acting, which in turn temporarily relieves histamine-related negative symptoms (such as watery eyes and nasal congestion). [1]

Children aged 6-11 months:

a) Oral Solution - 2 mL (1 mg) once a day

Children aged 12 months-5 years:

a) Oral Solution - 1/2 teaspoonful (1.25 mg in 2.5 mL) once a day

Children aged 6-11 years:

a) Tablets - one 2.5 mg tablet once a day

b) Oral Solution - 1 tbsp (2.5 mg in 5 mL) once a day

Adolescents and adults ≥ 12 years of age:

a) Oral Solution - 2 tbsps (5 mg in 10 mL) once a day

b) Tablets - 1 tablet (5 mg) once a day

c) Tablets - 1 tablet (5 mg) once a day [3]

Absorption

Healthy volunteers who received a 5 mg tablet of desloratadine orally once a day for ten days reported a mean steady-state AUC of 56.9 ng*hr/ml, a mean steady-state Cmax of 4 ng/ml, and a mean Tmax of around three hours. Utilizing 10 ml of an oral solution containing desloratadine (5 mg), a similar profile was seen. Desloratadine absorption was shown not to be influenced by food.

Volume of distribution

Not Available

Protein binding

Plasma proteins bind desloratadine between 82-87%. On the other hand, 3-hydroxydesloratadine (the active metabolite) is bound to plasma proteins by around 85-89%.

Metabolism

The active metabolite of desloratadine, 3-hydroxydesloratadine, is produced during the process of metabolism and is then glucuronidated.

Route of elimination

Urine and faeces both contained over 87% of a dosage of 14C-desloratadine that was retrieved as  metabolic byproducts.

Half-life

Desloratadine's mean plasma elimination half-life is about 27 hours.

Clearance

Not Available [1]

Patients who are hypersensitive to desloratadine, any of its constituents, or loratadine should not use it. [3]

Cimetidine

Desloratadine and 3 hydroxydesloratadine plasma concentrations rose when desloratadine and cimetidine, a histamine H2-receptor antagonist, were administered together in controlled clinical trials, although the safety profile of desloratadine was unaffected.

Fluoxetine

Desloratadine and 3 hydroxydesloratadine plasma concentrations elevated when fluoxetine, a selective serotonin reuptake inhibitor (SSRI), were administered together in controlled clinical investigations. However, there were no clinically meaningful alterations in desloratadine's safety profile.

Inhibitors of Cytochrome P450 3A4

Desloratadine and its 3 hydroxy derivatives were shown to have higher plasma concentrations when azithromycin, erythromycin, or ketoconazole were co-administered in controlled clinical trials, although there were no statistically significant alterations in desloratadine's safety profile.  [3]

The most commonly noted adverse reactions (noted in ≥2% of adults and adolescents with allergic rhinitis) were:

Dysmenorrhea

Somnolence

Fatigue

Myalgia

Dry mouth

Pharyngitis [3]

• Patients who have a medical or family history of seizures, especially young children, should be treated with desloratadine with caution since they are more likely to experience new seizures as a result of the medication. Discontinue Desloratadine in individuals who experience a seizure while on treatment. [4]  
• There have been reports of hypersensitivity responses that include rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis. In such circumstances, the use of Desloratadine must be stopped. [3]

(A)   Allergic rhinitis

An open-label trial by Tamer MH Adham showed that 5 mg/day desloratadine for 2 weeks is both safe and effective for easing ocular and nasal symptoms as well as enhancing nasal airflow in patients with moderate-to-severe allergic rhinitis. Desloratadine considerably decreased mean nasal and total ocular symptom scores as well as total symptom score (TSS) after 2 weeks of therapy. The peak nasal inspiratory flow (PNIF) measures of nasal congestion dramatically enhanced post-treatment. Majority of individuals had complete (38.1%) or marked (47.2%) reduction in allergic rhinitis symptoms. No adverse events were reported. [5]  

Another study evaluated the safety and effectiveness of Desloratadine in people with persistent allergic rhinitis. Volunteers aged ≥12 years suffering from persistent allergic rhinitis were evaluated after receiving Desloratadine 5 mg once daily (n = 360) or a placebo (n = 356) for 85 days. The study showed that Desloratadine is efficient, improves quality of life, and has a favorable safety profile.

The mean decline in the AM/PM reflective total 5-symptom score (T5SS) was considerably higher with Desloratadine use when compared to placebo over days 1-29 (-3.76 vs. -2.87) and on each of the individual day. The mean AM instantaneous T5SS was remarkably decreased with Desloratadine in comparison with placebo as early as day 2 (-1.90 vs. -1.46). [6]

(B)  Chronic urticaria

According to the findings of a meta-analysis, Desloratadine is efficient and safe in the management of chronic urticaria. Overall, 4972 volunteers from 47 studies were included in this study. In comparison to other antihistamine agents, desloratadine had a better impact on the improvement of signs and symptoms (RR=1.06). [7]

According to a  randomized, double-blind, placebo-controlled trial, 5 mg once daily desloratadine is an effective and well-tolerated treatment for chronic idiopathic urticaria. It elicited remarkable improvements in the number of hives, pruritus, the size of the largest hive, and total chronic idiopathic urticaria symptom score. [8]

Desloratadine 5 mg daily is an efficient and safe intervention for chronic idiopathic urticaria, with substantial advantages within 24 hours of administration and maintained throughout the treatment period, according to a double-blind, randomized trial with 190 subjects (12-79 years of age), with at least a 6-week history of chronic idiopathic urticaria.

After the first dose, desloratadine was more effective than the placebo in mitigating pruritus and total symptoms, and it continued to be more effective through the study's conclusion. After the first dose, it also significantly improved measures of sleep, daily activity, therapeutic response, and overall chronic idiopathic urticaria status; these clinical advantages persisted throughout the 6-week study. There were no noteworthy negative incidents. [9]

1. Desloratadine. Drug Bank. Accession Number DB00967. Available online from: https://go.drugbank.com/drugs/DB00967

[Last accessed on: 15 December 2022]

2. Murdoch D, Goa KL, Keam SJ. Desloratadine: an update of its efficacy in the management of allergic disorders. Drugs. 2003;63(19):2051-2077.

3. Desloratadine. FDA LABEL. Available online from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021165s017,021300s014,021312s015,021563s003lbl.pdf

[Last accessed on: 15 December 2022]

4. Ersbøll AK, Sengupta K, Pukkala E, Bolin K, Aas E, Emneus M et al. Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015. Drug Saf. 2021 Nov;44(11):1231-1242.

5. Adham TM. Treatment of allergic rhinitis with desloratadine: results of a multinational observational study in the middle East gulf region. World Allergy Organ J. 2011 Aug;4(8):130-134.

6. Bousquet J, Bachert C, Canonica GW, Mullol J, Van Cauwenberge P, Jensen CB et al. Efficacy of desloratadine in persistent allergic rhinitis - a GA²LEN study. Int Arch Allergy Immunol. 2010;153(4):395-402.

7. Gang L, Haiyan W, Lifeng M, Jinchun S. Efficacy and safety of desloretadine in chronic urticarial: a meta analysis. Clinical Focus. 2019 Aug 20;34(8):752.

8. Monroe E, Finn A, Patel P, Guerrero R, Ratner P, Bernstein D. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. 2003 Apr;48(4):535-41.

9. Ring J, Hein R, Gauger A, Bronsky E, Miller B. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. Int J Dermatol. 2001 Jan;40(1):72-6.