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DESLORATADINE

Summary
Desloratadine, which is the major active metabolite of loratadine, is a non-sedating histamine H1 antagonist. It is licensed for the relief of symptoms associated with seasonal allergic rhinitis (SAR). Published efficacy data are limited. There are no comparative studies with other antihistamines but the clinical efficacy compared to placebo seems similar to established antihistamines. The European Public Assessment Report on desloratadine states that the efficacy of 5mg desloratadine is probably not superior to 10mg of loratadine. The manufacturer suggests that desloratadine, unlike other antihistamines, relieves the nasal congestion associated with SAR. It is not possible to determine whether this is a true clinical advantage without comparative studies. Treatment with desloratadine 5mg daily for 30 days costs 7.57 which is exactly the same as the cost of the parent drug, loratadine. However, the patent on loratadine is due to expire at the end of 2002 and it is expected that cheaper, generic formulations will then become available.

Date Published: June 2001

Monograph Number: 4/01/06

Marketed: February 2001

Region of origin to whom queries should be directed: Glasgow (Scotland) The information contained in this document will be superseded in due course. Not to be used for commercial purposes Copyright MIPG 2001 Web site http://www.ukmi.nhs.uk/med_info/stage4.html

DESLORATADINE

Approved Name : Brand Name (Manufacturer): Presentation: BNF Therapeutic Class: Licensed Indications:

Desloratadine Neoclarityn (Schering-Plough) Film-coated tablets containing 5mg desloratadine 3.4.1 Antihistamines The relief of symptoms associated with seasonal allergic rhinitis

Dosage and Administration:

Adults and adolescents (12 years and over): one tablet daily with or without a meal

Sector of Use:

Hospital [Y] Primary Care [Y]

Therapeutic Comment:

Desloratadine, as the major active metabolite of loratadine, offers no confirmed advantages over other non-sedating antihistamines.

Cost and Course Details:

Desloratadine 5mg daily costs 7.57 for 30 days treatment

Treatment Alternatives: [comparative costs for 30 days treatment] MIMS April 2001

Loratadine 10mg daily Cetirizine 10mg daily

7.57 8.73

Fexofenadine 120mg daily 7.40 Mizolastine 10mg daily Chlorpheniramine 4mg tid 8.55 0.85

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DESLORATADINE
INTRODUCTION
Seasonal allergic rhinitis (SAR) or hay fever is an IgE-mediated inflammatory disease of the nasal mucosa characterised by symptoms of sneezing, rhinorrhoea (runny nose), nasal congestion and nasal pruritus [1-3]. SAR may be accompanied by itching of the throat, eyes and ears and oedema around the eyes. Around 20% of cases are

PHARMACOKINETICS
Desloratadine is well absorbed with maximum plasma concentrations reached within about 3 hours; the terminal elimination half-life is

approximately 27 hours [5]. Food has no effect on the extent of absorption [6]. Desloratadine is primarily metabolised by hydroxylation and

excreted mainly in the urine as metabolites. There is no evidence of clinically relevant drug

accompanied by asthma. Allergy to grass pollen is the most common cause of hay fever in the UK. The prevalence of SAR amongst patients

accumulation following once daily dosing of desloratadine (5mg to 20mg) for 14 days. Pharmacokinetic studies with desloratadine in the elderly and in patients with renal dysfunction are not available. However, it has been reported safe and effective in SAR patients up to 75 years of age, suggesting no need for dose adjustment in the elderly [7]. The available data for loratadine indicate that the elimination half-life of

attending GPs is 20 per thousand in the UK. Incidence is highest among young adults and teenagers; it is rare for the elderly to be affected. Avoiding allergen exposure is the most effective way of controlling allergic conditions; however, in SAR total avoidance is almost impossible and pharmacological treatment may be needed.

Choice of drug treatment depends mainly on predominant symptoms and patients' preference for topical or oral therapy. The mainstays of

desloratadine may be increased in patients with chronic renal failure [4]. However, dosage

reduction in mild to moderate renal impairment is probably not necessary. Desloratadine should be used with caution in severe renal impairment [5]. Limited pharmacokinetic data suggest that

treatment are intranasal corticosteroids and oral antihistamines [2].

PHARMACOLOGY
Desloratadine is a selective peripheral long-acting, histamine non-sedating, H1-receptor

desloratadine 5mg daily is likely to be safe in patients with hepatic dysfunction [6].

antagonist; it is the major active metabolite of the parent drug loratadine. Desloratadine acts by inhibiting the release of pro-inflammatory In

EFFICACY
Published data on the clinical efficacy of

mediators from human mast cells/basophils.

desloratadine are limited; two efficacy studies are reported in one paper and other data are published as abstracts only. Meltzer et al

pre-clinical studies it was more potent than loratadine or terfenadine as an antagonist at H 1 receptors and it was more potent than loratadine with respect to in vivo inhibition of histamineinduced wheal and flare [4]. It does not readily penetrate the central nervous system. At the

described two randomised, double-blind, placebocontrolled studies in patients with at least a 2 year history of moderate to severe SAR and positive skin tests [8]. Both studies were conducted in the USA, one in spring (n=346) and one in autumn (n=328). Inclusion and exclusion criteria are given in table 1. Study results were analysed according to intention to treat. Baseline symptom scores

recommended dose of 5mg daily there was no excess incidence of somnolence as compared to placebo. Single daily doses of 7.5mg did not

affect psychomotor performance in clinical trials [5].

were determined from a 3-day run-in period Page 3 of 6

DESLORATADINE
before the start of therapy. Patients were then suggests that the efficacy of 5mg desloratadine is probably not superior to 10mg loratadine [3].

randomised to receive desloratadine 5mg once daily or placebo for 14 days. The primary endpoint was the mean change during days 2-15 from baseline in the total symptom score (TSS) averaged over the 2 week study period. In the spring study (April to June) 172 patients were randomised to desloratadine and 174 to placebo. Desloratadine reduced the TSS by 4.3 (range 3.7 - 4.8), a 28% reduction from baseline, over the study period. The corresponding

PROMOTIONAL DATA
Currently available antihistamines are perceived to lack decongestant efficacy and the

manufacturer claims that desloratadine may be superior in this regard [9,10]. This claim cannot be fully evaluated on the basis of available data and comparisons with loratadine and other agents will be needed to confirm whether this is a true clinical advantage.

decrease in TSS with placebo was 2.5 (range 1.6 - 3.2), a 12.5% reduction (p<0.01). No confidence intervals for the treatment effect were given. Five patients in the desloratadine group discontinued treatment due to adverse events versus 10 in the placebo group. In the autumn study (August to November) 164 patients were randomised to desloratadine and 164 to placebo. The TSS was reduced by 5.1

ADVERSE EFFECTS
Desloratadine was well tolerated during clinical trials involving more than 2000 patients;

undesirable effects were reported in 4% of patients in excess of those treated with placebo. Headache (6%), dry mouth (3%) and fatigue (3%) were the most common adverse effects [11]. No excess incidence of somnolence/sedation was reported. No significant ECG or other adverse

(30%) and 3.8 (22%) in the desloratadine and placebo groups respectively (p=0.02). No

cardiovascular effects have been reported with desloratadine. No adverse effect on

confidence intervals for the treatment effect were given. Five patients in each group discontinued treatment. In both studies symptom improvement with desloratadine was evident after only one dose and was maintained for the full 24 hour treatment interval. Pooled including data from four unpublished studies with

cardiovascular function was observed in healthy volunteers with desloratadine in doses of up to 20mg daily for 14 days or at 45mg daily for 10 days [12].

over

600

patients

treated

CONTRAINDICATIONS / PRECAUTIONS
Desloratadine is contraindicated in patients with known hypersensitivity to desloratadine, any of the excipients or to loratadine. It should not be used in pregnancy unless the potential benefits outweigh the risks [5]. Clinical data on pregnancy outcome in women exposed to desloratadine are not available although no teratogenic or mutagenic effects were observed in animal studies. Pregnancy outcome data after exposure to loratadine is also too limited to allow an assessment of any teratogenic risk.

desloratadine 5mg suggest that it may have a decongestant effect in SAR [9]. Desloratadine was associated with significantly greater improvement in nasal congestion from than placebo p=0.02) (a 25%

decrease

baseline,

although

symptom severity scores were not reported. This finding requires confirmation in published studies. The European Public Assessment Report summarises the findings of four efficacy studies in over 2000 patients. It concludes that desloratadine 5mg is effective in SAR but Page 4 of 6

DESLORATADINE
As desloratadine is excreted into breast milk it is not recommended for use in breastfeeding women [5]. Desloratadine should be used with caution in patients with severe renal impairment. No relevant drug interactions were observed in clinical trials in which erythromycin or ketoconazole were given together with
11. Schering-Plough. Neoclarityn. Product Monograph 2001 12. Marino M, Glue P, Herron JM et al. Lack of electrocardiographic effects of multiple high doses of desloratadine. Poster presented at EAACI, Lisbon, Portugal, 2-4 July 2000

desloratadine [5].

However as the enzyme

responsible for desloratadines metabolism has not been clearly identified, the potential for interactions with other drugs cannot be excluded.

REFERENCES
1. 2. 3. Durham S. Summer hay fever. BMJ 1998; 316: 843-845 Treatment of seasonal allergic rhinitis. MeReC bulletin 1998; 9(3): 9-12 Committee for Proprietary Medicinal Products. Neoclarityn. European Public Assessment Report (EPAR). European Agency for the Evaluation of Medicinal Products. March 2001 Desloratadine. (Drug Evaluation) in: Hutchison TA, Shahan DR and Anderson ML (Eds): DRUGDEX system. Micromedex Inc., Greenwood Village, Colorado (Edition expires June 2001). Schering-Plough. Neoclarityn. Summary of Product Characteristics, January 2001 Henz BM. The pharmacologic profile of desloratadine: a review. Allergy 2001; 56: 7-13 Salmun LM, Lorber R, Danzig M et al. Efficacy and safety of desloratadine in seasonal allergic rhinitis (abstract 1123). J Allergy Clin Immunol 2000; 104: S384 Meltzer EO, Prenner BM, Nayak A and the Desloratadine Study Group. Efficacy and tolerability of once-daily 5mg desloratadine, an H1receptor antagonist, in patients with seasonal allergic rhinitis. Clin Drug Invest 2001; 21: 25-32. Nayak A, Schenkel E, Salmun LM et al. Desloratadine relieves nasal congestion in patients with seasonal allergic rhinitis. Poster presented at EAACI, Lisbon, Portugal, 2-4 July 2000

4.

5.

6. 7.

8.

9.

10. Bachert C. Decongestant efficacy of desloratadine in patients with seasonal allergic rhinitis. Allergy 2001; 56: 14-20

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DESLORATADINE
Table 1. Efficacy studies for desloratadine
Ref No
Meltzer EO et al [8] Spring study Inclusion criteria: At least 12 yrs old At least 2 yr history of moderate to severe SAR Positive skin prick tests Exclusion criteria: Rhinitis medicamentosa, Sinusitis, upper respiratory tract or sinus infection, other clinically significant diseases, pregnancy and breastfeeding. Patients taking asthma medication, nasal, oral or ocular decongestants, intranasal antihistamines, intranasal corticosteroids, and systemic antibiotics. Meltzer EO et al [8] Autumn study Inclusion and exclusion criteria: as above Baseline total symptom scores similar in both groups: Desloratadine 17.0 Placebo 17.1 Treatment period: 14 days Symptom assessment: as above Multicentre, randomised doubleblind Placebo-controlled study Baseline symptom score determined from 3 day run-in period Baseline total symptom scores similar in both groups: Desloratadine 14.2 Placebo 13.7 Symptoms during previous 12 hrs recorded twice a day (am and pm) Treatment period: 14 days

Design of Study
Multicentre, randomised doubleblind Placebo-controlled study

Treatments Assessed
Desloratadine 5mg (n=172) Placebo (n=174)

Major Outcome Measures

Primary endpoint was the mean change during days 2-15 from baseline in the average reflective 12 hour am/pm total symptom score (TSS). The TSS was determined as a sum of nasal (itching, stuffiness/congestion, rhinorrhoea and sneezing) and non-nasal (itching or burning eyes, itching of ears or palate, eye redness or tearing) symptom scores. Nasal and non-nasal symptom scores were also analysed separately

Results and Comments

Desloratadine 5mg TSS reduced by 4.3 (range 3.7 - 4.8) 28% reduction from baseline Placebo TSS reduced by 2.5 (range 1.6 - 3.2) 12.5% reduction from baseline p<0.01 Confidence intervals for treatment effect not reported

Desloratadine 5mg (n=164) Placebo (n=164)

Primary endpoint was the mean change during days 2-15 from baseline in the average reflective 12 hour am/pm total symptom score (TSS). The TSS was determined as a sum of nasal (itching, stuffiness/congestion, rhinorrhoea and sneezing) and non-nasal (itching or burning eyes, itching of ears or palate, eye redness or tearing) symptom scores. Nasal and non-nasal symptom scores were also analysed separately

Desloratadine 5mg TSS reduced by 5.1 30% reduction from baseline Placebo TSS reduced by 3.8 22% reduction from baseline p=0.02 Confidence intervals for treatment effect not reported

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