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Active ingredient: Fexofenadine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Antihistamines

Dosage Forms

  • Oral tablets
  • Capsules

Brands / Synonyms

Allegra; Allegra D; Allegra D-12 Hour; Allegra-D; Allegra-D 24 Hour; Carboxyterfenadine; Fexofenadine; Fexofenadine hydrochloride; Fexofendine; Terfenadine acid metabolite; Terfenadine carboxylate; Terfenadine-COOH

Indications

For management of Seasonal allergic rhinitis

Pharmacology

Fexofenadine is a second-generation, long lasting H1-receptor antagonist (antihistamine) which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, for example, swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergy. Fexofenadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Fexofenadine does not enter the brain from the blood and, therefore, does not cause drowsiness. Fexofenadine lacks the cardiotoxic potential, since it does not block the potassium channel involved in repolarization of cardiac cells.

Mechanism of Action

Like other H1-blockers, Fexofenadine competes with free histamine for binding at H1-receptors in the GI tract, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Fexofenadine exhibits no anticholinergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects.

Absorption

33%

Toxicity

Side effects include dizziness, drowsiness, and dry mouth.

Biotrnasformation / Drug Metabolism

Approximately 5% of the total dose is metabolized, by cytochrome P450 3A4 and by intestinal microflora.

Contraindications

ALLEGRA is contraindicated in patients with known hypersensitivity to any of its ingredients.

Drug Interactions

Drug Interaction with Erythromycin and Ketoconazole

Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, coñ administration of fexofenadine hydrochloride with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies, fexofenadine hydrochloride 120 mg twice daily (240 mg total daily dose) was co-administered with either erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to healthy volunteers (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine hydrochloride alone or in combination with either 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
(two times the recommended twice daily dose) in healthy volunteers (n=24)

Concomitant Drug

cmaxSS (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. This observed increase in the bioavailability of fexofenadine may be due to transport-related effects, such as p-glycoprotein. in vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion.

Drug Interactions with Antacids

Administration of 120 mg of fexofenadine hydrochloride (2 x 60 mg capsule) within 15 minutes of an aluminum and magnesium containing antacid (Maalox®) decreased fexofenadine AUC by 41% and cmax by 43%. ALLEGRA should not be taken closely in time with aluminum and magnesium containing antacids.

Interactions with Fruit Juices

Fruit juices such as grapefruit, orange and apple may reduce the bioavailability and exposure of fexofenadine. This is based on the results from 3 clinical studies using histamine induced skin wheals and flares coupled with population pharmacokinetic analysis. The size of wheal and flare were significantly larger when fexofenadine hydrochloride was administered with either grapefruit or orange juices compared to water. Based on the literature reports, the same effects may be extrapolated to other fruit juices such as apple juice. The clinical significance of these observations is unknown. In addition, based on the population pharmacokinetics analysis of the combined data from grapefruit and orange juices studies with the data from a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Therefore, to maximize the effects of fexofenadine, it is recommended that ALLEGRA should be taken with water.

 

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