Loratadine (Claritin)
Alavert™, Claritin®, Claritin® Hives Relief, Claritin® Reditab®, Dimetapp® ND Non-Drowsy Allergy ODT, Dimetapp® ND Non-Drowsy Allergy Syrup | Allergy Relief | Children’s Alavert™ Syrup | Children’s Dimetapp® ND Non-Drowsy Allergy Liquid | Children’s Dimetapp® ND Non-Drowsy Allergy Tablets | Childrens Claritin® | Clear-Atadine™ | Clear-Atadine™ Childrens | Equate® Allergy Relief 24 Hour | Major Allergy Syrup | Tavist® ND | Triaminic® AllerChews™
Classification:
Antihistamines
H1-blockers
Description: Loratadine is an oral non-sedating H1-blocker that is similar in structure to cyproheptadine and azatadine, other H1-blockers. Loratadine differs structurally from the other non-sedating H1-blockers terfenadine and astemizole. Due to poor penetration into the CNS and a low affinity for CNS H1-receptors, the CNS effects are less with loratadine compared to the traditional H1-blockers. Loratadine can be administered once daily. Unlike astemizole and terfenadine, loratadine has not been associated QT prolongation or torsades de pointes. Loratadine was approved by the FDA in April 1993 to relieve the symptoms associated with seasonal allergic rhinitis. In December 1996, a rapidly-disintegrating dosage form was approved. In December 2000, loratadine received FDA approval for use in children aged >=2 years. An analog known as ‘desloratadine’ was approved by the FDA in December 2001. The US patent for Claritin® expired in 2002; all product formulations are anticipated to be available generically by April 2004. The FDA approved the non-prescription (OTC) use of Claritin® (all formulations) for the treatment of seasonal allergic rhinitis on November 27, 2002. Previously only available by prescription, loratadine products became available for OTC sale during December 2002. Alavert™ oral disintegrating tablets were FDA approved in December 2002. Generic formulations of Claritin® tablets and Claritin® Reditabs were approved during February 2003. The generic version of Claritin® oral syrup was approved during November 2003.
Mechanism of Action: Similar to other H1-blockers, loratadine 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 muscle. Loratadine 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, loratadine does not exert significant anticholinergic effects at therapeutic concentrations. In vitro studies have shown that loratadine has a weak affinity for acetylcholine and alpha-adrenergic receptors.
Claritin Tablets (Tab 10 mg)
Pharmacokinetics: Loratadine is administered orally. The onset of action of loratadine occurs within 1 - 3 hours, with peak effects in 8 - 12 hours and a duration of action greater than 24 hours. Administration with food increases absorption and AUC up to 40% for the syrup or tablets and up to 48% for the rapidly-disintegrating tablets. The time to peak concentrations is also delayed by administration with food. However, since the clinical response is unaffected, the manufacturer states that the drug can be administered without regard to meals. Loratadine is 97% protein-bound and is excreted into breast milk. Loratadine has a high first pass effect and is almost completely metabolized in the liver to the minimally active metabolite, descarboethoxyloratadine. In vitro studies indicate that loratadine is metabolized to descarboethoxyloratadine predominantly by CYP3A4 and, to a lesser extent, by cytochrome CYP2D6. In the presence of a CYP3A4 inhibitor, loratadine is metabolized to descarboethoxyloratadine predominantly by CYP2D6. Concurrent administration of loratadine with either ketoconazole, erythromycin (both CYP3A4 inhibitors), or cimetidine (CYP2D6 and CYP3A4 inhibitor) to healthy volunteers was associated with increased plasma concentrations of loratadine. The normal mean elimination half-lives of loratadine and its metabolite are 8.4 hours (range 3 - 20 hours) and 28 hours, respectively. Elimination occurs through the fecal and renal routes.
Special Populations: In healthy children who are administered age and weight-adjusted dosages, loratadine pharmacokinetic profiles are similar to those of adults. In elderly subjects, the AUC and peak plasma concentrations of loratadine are roughly 50% greater than those observed in young adults. The elderly have prolonged elimination half lives for both the parent drug (18.2 hours) and its metabolite (17.5 hours). However, no dosage adjustments in the elderly are considered necessary.
Loratadine dosages should be altered in patients with hepatic or renal impairment (CrCl < 30 ml/min). Patients with chronic alcoholic liver disease achieve peak serum concentrations which are approximately double those observed in normal controls. Those with chronic alcoholic liver disease will have prolonged elimination half lives for both the parent drug (24 hours) and its metabolite (37 hours), and increased with the severity of the hepatic impairment. Peak serum concentrations of loratadine may increase up to 73% in the presence of renal impairment; although elimination half-lives are similar to those of normal controls. Hemodialysis does not alter the pharmacokinetics of loratadine or its metabolite.
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[ Revised 5/8/2006 6:07:00 PM ]
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