Clarinex - Side Effects & Drug Interactions

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In 3 separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n= 18) or with fluoxetine 20 mg once daily for 7 days after a 23 day pretreatment period with fluoxetine (n= 18) or with cimetidine 600 mg every 12 hours for 14 days (n= 18) under steady state conditions to normal healthy male and female volunteers.

Although increased plasma concentrations (Cmax and AUC 0-24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see Table 1), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.

Table 1

Changes in Desloratadine and 3-Hydroxydesloratadine Pharmacokinetics in Healthy Male and Female Volunteers

Desloratadine 3-Hydroxydesloratadine

AUC AUC Cmax 0-24 hrs Cmax 0-24 hrs

Erythromycin (500 mg Q8h) +24% +14% +43% +40%

Ketoconazole (200 mg Q12h) +45% +39% +43% +72%

Azithromycin (500 mg day 1, 250 mg QD x 4 days) +15% +5% +15% +4%

Fluoxetine (20 mg QD) +15% +0% +17% +13%

Cimetidine (600 mg Q12h) +12% +19% -11% -3%

Pharmacodynamics:

Wheal and Flare:

Human histamine skin wheal studies following single and repeated 5 mg doses of desloratadine have shown that the drug exhibits an antihistaminic effect by 1 hour; this activity may persist for as long as 24 hours. There was no evidence of histamine-induced skin wheal tachyphy-laxis within the desloratadine 5 mg group over the 28 day treatment period. The clinical relevance of histamine wheal skin testing is unknown.

Effects on QTc:

Single dose administration of desloratadine did not alter the corrected QT interval (QTc) in rats (up to 12 mg/ kg, oral), or guinea pigs (25 mg/ kg, intravenous). Repeated oral administration at doses up to 24 mg/ kg for durations up to 3 months in monkeys did not alter the QTc at an estimated desloratadine exposure (AUC) that was approximately 955 times the mean AUC in humans at the recommended daily oral dose. See OVERDOSAGE section for information on human QTc experience.