Pharmacology Update: Desloratadine Tablets (Clarinex)
March 15, 2002
Desloratadine Tablets (Clarinex)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
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Schering has received approval to market desloratadine for the treatment of allergic rhinitis and chronic idiopathic urticaria. Desloratadine is the primary active metabolite of loratadine (Claritin) and shares much of the same therapeutic properties. Schering is losing exclusivity on loratadine later this year when the drug’s patent expires, and the company hopes to recover some of their lost revenue stream by the introduction of this new nonsedating antihistamine. Desloratadine will be marketed under the trade name "Clarinex" and is expected to be heavily promoted.
Indications
Desloratadine is indicated for the relief of the nasal and non-nasal symptoms of allergic rhinitis (seasonal and perennial) in patient 12 years of age and older. It is also indicated for the symptomatic relief of pruritus, reduction in the number of hives, and size of hives, in patients with chronic idiopathic urticaria 12 years of age and older.1
Dosage
The recommended dose is 5 mg daily and may be taken without regard to meals. In patients with liver or renal impairment, a starting dose of 5 mg every other day is recommended.1
Desloratadine is supplied as 5 mg tablets.
Potential Advantages
Desloratadine does not appear to have any significant pharmacokinetic or pharmacodynamic drug-drug or drug-food (eg, grapefruit juice) interactions involving the cytochrome P450 enzyme system or the drug transporters systems (organic anion transporting peptide, P-glycoprotein).2-4 Desloratadine is less likely to inhibit P-glycoprotein than loratadine.3 In vitro studies and animal models indicate that desloratadine has more potent antihistaminic activity than loratadine,5 however the relative potency in vivo has not been reported.
Desloratadine does not appear to potentiate the effect of alcohol.6
Potential Disadvantages
The bioavailability of desloratadine is increased by 1.2-1.9 fold in patients with mild-to-moderate renal impairment and a 2.4-fold increase in patient with hepatic impairment, regardless of severity.1 Dose reduction is recommended in these patients. Common side effects (incidence vs placebo) include pharyngitis 4.1% vs. 2.0% and dry mouth 3.0% vs. 1.9%.1
There are no comparative studies with other non-sedating histamine-1 receptor antagonists. The relative effectiveness or tolerability is not known.
Comments
Desloratadine is the primary metabolite of loratadine. It has no apparent cardiovascular toxicity, does not appear to cause sedation, or impair cognitive or psychomotor performance.5 The available evidence of efficacy of desloratadine is based on placebo-controlled trials in about 4000 patients. In 2-week studies, patients with seasonal allergic rhinitis (SAR), desloratadine was reported to improve health-related quality of life as evaluated by the Short-Form 36, Rhinoconjunctivitis quality of life, or total symptom score (TSS) compared to placebo.7,8 Reduction in TSS for spring (n = 346) or fall allergy (n = 328) season ranged from 28-30% for desloratadine 5 mg daily compared to 13-22% for placebo, P < 0.01 to P = 0.02. Reduction was statistically significant beginning on day 2 and maintained for the study period. Desloratadine use has also been reported to result in modest improvement in nasal congestion/stuffiness, 21-24% reduction compared to 14-16% for placebo, P < 0.05.8,9 In 2 4-week trials, desloratadine was reported to show improvement in asthma symptoms and reduced bronchodilator use in patients with concomitant SAR and mild-to-moderate asthma.8
In a 4-week study, patients with perennial allergic rhinitis had a reduction of TSS of 4.06 (-33%) with desloratadine (n = 327) compared to 3.27 (-27%) for placebo (n = 337; P < 0.01).1
Desloratadine has also been reported to improve symptoms associated with chronic idiopathic urticaria compared to placebo.10 The morning and evening pruritus score and TSS (pruritus, number of hives, and size of the largest hives) as assessed by the patient were significantly improved compared to placebo. Over the first week, there was a 56% reduction from baseline in pruritus score compared to 21.5% for placebo and 51.6% reduction in TSS compared to 19.3%.
Desloratadine is initially priced less than loratadine ($1.83 vs $2.22 per day) to gain market share before the patent expiration of loratadine in December.
Clinical Implications
As the primary metabolite of loratadine, desloratadine does not appear to have any dramatic advantage over its parent compound that is going generic. Desloratadine is approved for perennial allergic rhinitis while loratadine is not. This is expected to be a key marketing point for Schering. Without comparative trials its efficacy or tolerability compared to other nonsedating histamine-1 receptor antagonists is not known.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
References
1. Clarinex Product Information. Schering-Plough. February 2002.
2. Barecki ME, et al. Drug Metab Dispos. 2001;29:1173-1175.
3. Wang EJ, et al. Drug Metab Dispos. 2001;29:1080-1083.
4. Agrawal DK, et al. Expert Opin Investig Drugs. 2001; 10(3):547-60.
5. McClellan K, Jarvis B. Drugs. 2001;61(6):789-796.
6. Scharf M, et al. J Allergy Clin Immunol. 2000;5(1, part 2, supplement):S394 (abstract).
7. Meltzer EO, et al. Clin Drug Invest. 2001;21(1):25-32.
8. Geha RS, Meltzer EO. J Allergy Clin Immunol. 2001; 107(4):751-762.
9. Nayak AS, et al. Allergy. 2001;56(11):1077-1080.
10. Ring J, et al. Int J Dermatol. 2001;40:72-76.
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