Allegra - Clinical Pharmacology

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Hepatic Impairment.

The pharmacokinetics of fexofenadine hydrochloride in patients with hepatic disease did not differ substantially from that observed in healthy patients.

Effect of Gender.

Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine hydrochloride.

Pharmacodynamics

Wheal and Flare.

Human histamine skin wheal and flare studies following single and twice daily doses of 20 and 40 mg fexofenadine hydrochloride demonstrated that the drug exhibits an antihistamine effect by 1 hour, achieves maximum effect at 2 to 3 hours, and an effect is still seen at 12 hours. There was no evidence of tolerance to these effects after 28 days of dosing. Histamine skin wheal and flare studies in 7 to 12 year old patients showed that following a single dose of 30 or 60 mg, antihistamine effect was observed at 1 hour and reached a maximum by 3 hours. Greater than 49% inhibition of wheal area, and 74% inhibition of flare area were maintained for 8 hours following the 30 and 60 mg dose. Effects on QTc. In dogs (30 mg/kg/orally twice a day), and in rabbits (10 mg/kg, infused intravenously over 1 hour) fexofenadine hydrochloride did not prolong QTc.

In dogs, the plasma fexofenadine concentration was approximately 9 times the therapeutic plasma concentrations in adults receiving the maximum recommended daily oral dose. In rabbits, the plasma fexofenadine concentration was approximately 20 times the therapeutic plasma concentration in adults receiving the maximum recommended daily oral dose. No effect was observed on calcium channel current, delayed potassium channel current, or action potential duration in guinea pig myocytes, sodium current in rat neonatal myocytes, or on several delayed rectifier potassium channels cloned from human heart at concentrations up to 1 x 10-5 M of fexofenadine hydrochloride.

No statistically significant increase in mean QTc interval compared to placebo was observed in 714 seasonal allergic rhinitis patients given fexofenadine hydrochloride capsules in doses of 60 to 240 mg twice daily for two weeks. Pediatric patients from two placebo controlled trials (n=855) treated with up to 60 mg fexofenadine hydrochloride twice daily demonstrated no significant treatment or dose-related increases in QTc. In addition, no statistically significant increase in mean QTc interval compared to placebo was observed in 40 healthy volunteers given fexofenadine hydrochloride as an oral solution at doses up to 400 mg twice daily for 6 days, or in 231 healthy volunteers given fexofenadine hydrochloride 240 mg once daily for 1 year.