Allegra D - Warnings & Precautions

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Drug Interactions

Fexofenadine hydrochloride and pseudoephedrine hydrochloride do not influence the pharmacokinetics of each other when administered concomitantly.

Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co-administration of fexofenadine with ketoconazole and erythromycin led to increased plasma levels of fexofenadine. Fexofenadine had no effect on the pharmacokinetics of erythromycin and ketoconazole. In two separate studies, fexofenadine HCl 120 mg BID (twice the recommended dose) was co-administered with erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to normal, healthy volunteers (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine HCl alone or in combination with erythromycin or ketoconazole. The findings of these studies are summarized in the following table.

Effects on Steady-State Fexofenadine Pharmacokinetics

After 7 Days of Co-Administration with Fexofenadine Hydrochloride 120 mg Every 12 Hours (twice recommended dose) in Normal Volunteers (n=24) Concomitant DrugCmax SS (Peak plasma concentration) AUCSS(0-12h) (Extent of systemic exposure)Erythromycin (500 mg every 8 hrs)+82%+109%Ketoconazole (400 mg once daily)+135%+164%The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials.

The mechanism of these interactions has been evaluated in in vitro, in situ and in vivo animal models. These studies indicate that ketoconazole or erythromycin co-administration enhances fexofenadine gastrointestinal absorption. In vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion.

ALLEGRA-D tablets (pseudoephedrine component) are contraindicated in patients taking monoamine oxidase inhibitors and for 14 days after stopping use of an MAO inhibitor. Concomitant use with antihypertensive drugs which interfere with sympathetic activity (eg, methyldopa, mecamylamine, and reserpine) may reduce their antihypertensive effects. Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis.