Loratadine is a long-acting tricyclic antihistamine with selective peripheral histamine H₁-receptor antagonistic activity.

Human histamine skin wheal studies following single and repeated 10 mg oral doses of CLARITIN have shown that the drug exhibits an antihistaminic effect beginning within 1 to 3 hours, reaching a maximum at 8 to 12 hours, and lasting in excess of 24 hours. There was no evidence of tolerance to this effect after 28 days of dosing with CLARITIN.

Whole body autoradiographic studies in rats and monkeys, radiolabeled tissue distribution studies in mice and rats, and in vivoradioligand studies in mice have shown that neither loratadine nor its metabolites readily cross the blood-brain barrier. Radioligand binding studies with guinea pig pulmonary and brain H₁-receptors indicate that there was preferential binding to peripheral versus central nervous system H₁-receptors.

Repeated application of CLARITIN REDITABS (loratadine rapidly-disintegrating tablets) to the hamster cheek pouch did not cause local irritation.

Pharmacokinetics: Absorption: Loratadine was rapidly absorbed following oral administration of 10 mg tablets, once daily for 10 days to healthy adult volunteers with times to maximum concentration (Tmax) of 1.3 hours for loratadine and 2.5 hours for its major active metabolite, descarboethoxyloratadine. Based on a cross-study comparison of single doses of loratadine syrup and tablets given to healthy adult volunteers, the plasma concentration profile of descarboethoxy-loratadine for the two formulations is comparable. The pharmacokinetics of loratadine and descarboethoxyloratadine are independent of dose over the dose range of 10 mg to 40 mg and are not altered by the duration of treatment. In a single-dose study, food increased the systemic bioavailability (AUC) of loratadine and descarboethoxyloratadine by approxi-mately 40% and 15%, respectively. The time to peak plasma concentration (Tmax) of loratadine and descarboethoxyloratadine was delayed by 1 hour. Peak plasma concentrations (Cmax) were not affected by food.

Pharmacokinetic studies showed that CLARITINREDITABS (loratadine rapidly-disintegrating tablets) provide plasma concentrations of loratadine and descarboethoxyloratadine similar to those achieved with CLARITIN Tablets. Following administration of 10 mg loratadine once daily for 10 days with each dosage form in a randomized crossover compari-son in 24 normal adult subjects, similar mean exposures (AUC) and peak plasma concentrations (Cmax) of loratadine were observed. CLARITINREDITABS (loratadine rapidly-disintegrating tablets)mean AUC and Cmax were 11% and 6% greater than that of the CLARITINTablet values, respectively. Descarboethoxyloratadine bioequivalence was demonstrated between the two formulations. After 10 days of dosing, mean peak plasma concentrations were attained at 1.3 hours and 2.3 hours (Tmax) for parent and metabolite, respectively.

In a single-dose study with CLARITIN REDITABS (loratadine rapidly-disintegrating tablets), food increased the AUC of loratadine by approximately 48% and did not appreciably affect the AUC of descarboethoxyloratadine. The times to peak plasma concentration (Tmax) of loratadine and descarboethoxyloratadine were delayed by approximately 2.4 and 3.7 hours, respectively, when food was consumed prior to CLARITIN REDITABS (loratadine rapidly-disintegrating tablets) administration. Parent and metabolite peak concentrations (Cmax) were not affected by food.

In a single-dose study with CLARITIN REDITABS (loratadine rapidly-disintegrating tablets) in 24 subjects, the AUC of loratadine was increased by 26% when administered without water compared to administration with water, while Cmax was not substantially affected. The bioavailability of descarboethoxyloratadine was not different when administered without water.

Metabolism: In vitrostudies with human liver microsomes indicate that loratadine is metabolized to descarboethoxy-loratadine predominantly by cytochrome P450 3A4 (CYP3A4) and, to a lesser extent, by cytochrome P450 2D6 (CYP2D6). In the presence of a CYP3A4 inhibitor ketoconazole, 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 substantially increased plasma concentrations of loratadine (see DRUG INTERACTIONS section).

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