Clarinex - Desloratadine
Clarinex® | Clarinex® RediTabs
Classification: Antihistamines
Description: Desloratadine is a non-sedating, potent, long-acting antihistamine, which acts upon peripheral histamine (H1) receptors. Due to poor penetration into the central nervous system (CNS) and a low affinity for CNS H1-receptors, CNS effects are less with desloratadine as compared to the traditional H1-antagonsits, such as diphenhydramine. Desloratadine is the active metabolite of loratadine, with a relative potency of 10-20 times that of loratadine in vitro. Both loratadine and desloratadine are non-sedating; however, desloratadine does not cause QT prolongation when given in doses 4-9 times the recommended dose in adults. Desloratadine is utilized in adults and adolescents to relieve symptoms associated with seasonal allergic rhinitis. Desloratadine is under review by the FDA for use in children > 2 years of age. Desloratadine is available as regular or rapidly disintegrating tablets. Desloratadine is available within Europe under the brand name Aerius?„?. Final FDA approval for desloratadine was given in December 2001. In February 2002, the FDA approved expanded indications for desloratadine including perennial allergic rhinitis and chronic idiopathic urticaria.
Mechanism of Action: Similar to other H1-blockers, desloratadine does not prevent the release of histamine as do cromolyn and nedocromil, but competes with free histamine for binding at the H1-receptor. This competitive antagonism blocks the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. At higher concentrations, H1-receptor antagonism becomes relatively irreversible. In vitro studies have demonstrated that desloratadine has a 15-fold higher affinity for the H1-receptor than does the parent compound, loratadine.
Desloratadine does not readily cross the blood-brain barrier, and it preferentially binds at H1-receptors in the periphery rather than within the brain, which probably accounts for some of its nonsedating character. H1-blockers are similar in structure to anticholinergics, local anesthetics, antispasmodics, and ganglionic- and adrenergic-blocking agents, sharing some of their properties. H1-blockers possess anticholinergic properties in varying degrees; however, desloratadine does not exert significant anticholinergic effects at therapeutic concentrations.
Pharmacokinetics: Desloratadine is administered orally. Peak plasma concentrations are obtained in 2-6 hours following a 5 mg or 7.5 mg dose of the conventional tablets. Food has no effect on the extent of desloratadine absorption. The 5 mg disintegrating tablet is bioequivalent to the 5 mg regular-release tablet. Desloratadine is extensively metabolized and only minimal amounts of the orally administered dose are recovered in the urine (< 2%) and feces (< 7%). The major metabolic pathway of desloratadine is hydroxylation to form 3-OH-desloratadine that is glucoronidated and the glucuronide conjugate is excreted in the urine and bile. The elimination plasma half-life is approximately 20-30 hours. Steady state plasma concentrations are attained in 4-6 days. AUC and Cmax values are not significantly different among race or gender, so no dosage adjustment among these groups is necessary. Slow metabolizers of desloratadine have been identified. In this patient population (which is estimated at 4%), half-lives are much longer (up to 60 hours), and median AUC values are approximately 6-fold higher. The major elimination pathway for slow metabolizers is via excretion of unchanged drug in the urine and feces.
Special Populations: Patients with hepatic impairment, regardless of severity, have demonstrated mean desloratadine AUC values 2.4 times greater than the normal patient population. An increase in the mean elimination half-life of desloratadine is observed in these patients. In patients with mild (creatinine clearance 51-69 ml/min/1.73 m2) or moderate (creatinine clearance 34-43 ml/min/1.73 m2) renal impairment the median Cmax and AUC values increased 1.2- and 1.9-fold, respectively relative to subjects with normal renal function. In patients with severe renal impairment or who were hemodialysis dependent, median Cmax and AUC values increase by approximately 1.7- and 2.5-fold, respectively. Minimal changes in 3-OH-desloratadine were observed. Dosage adjustments for patients with hepatic or renal impairment are recommended. Elderly patients (> 65 years old) have shown mean AUC and Cmax values which were 20% greater than in patients < 65 years old. The mean plasma elimination half-life was prolonged by approximately 30%. Dosage adjustment does not appear to be warranted in the elderly population.
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