Allegra - General Information
Allegra hydrochloride (Allegra) is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. It was developed as a successor of and alternative to terfenadine. Allegra, like other second and third-generation antihistamines, does not readily pass through the blood-brain barrier, and so causes less drowsiness than first-generation histamine-receptor antagonists.
Pharmacology of Allegra
Allegra 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. Allegra blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Allegra does not enter the brain from the blood and, therefore, does not cause drowsiness. Allegra lacks the cardiotoxic potential, since it does not block the potassium channel involved in repolarization of cardiac cells.
Allegra for patients
Patients taking ALLEGRA tablets should receive the following information:
ALLEGRA tablets are prescribed for the relief of symptoms of seasonal allergic rhinitis or for the relief of symptoms of chronic idiopathic urticaria (hives). Patients should be instructed to take ALLEGRA only as prescribed. Do not exceed the recommended dose. If any untoward effects occur while taking ALLEGRA, discontinue use and consult the doctor.
The product should not be used by patients who are hypersensitive to it or to any of its ingredients.
Patients should be told that this product should be used in pregnancy or lactation only if the potential benefit justifies the potential risk to the fetus or nursing infant.
Patients should be advised to take the tablet with water. Patients should also be advised to store the medication in a tightly closed container in a cool, dry place, away from children.
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)
cmaxSS (Peak plasma concentration)
AUCss(0-12h) (Extent of systemic exposure)
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.
ALLEGRA is contraindicated in patients with known hypersensitivity to any of its ingredients.
Additional information about Allegra
Allegra Indication: For management of Seasonal allergic rhinitis
Mechanism Of Action: Like other H1-blockers, Allegra 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. Allegra exhibits no anticholinergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects.
Drug Interactions: Cisapride Increased risk of cardiotoxicity and arrhythmias
Food Interactions: Take without regard to meals.
Grapefruit and grapefruit juice should be avoided throughout treatment as grapefruit can significantly decrease serum levels of this product.
Generic Name: Fexofenadine
Synonyms: Terfenadine-COOH; Terfenadine carboxylate; Terfenadine acid metabolite; Fexofenadine hydrochloride; Fexofendine; Carboxyterfenadine
Drug Category: Antihistamines
Drug Type: Small Molecule; Approved
Other Brand Names containing Fexofenadine: Allegra;
Toxicity (Overdose): Side effects include dizziness, drowsiness, and dry mouth.
Protein Binding: 60%-70%
Biotransformation: Approximately 5% of the total dose is metabolized, by cytochrome P450 3A4 and by intestinal microflora.
Half Life: 14.4 hours
Dosage Forms of Allegra: Tablet Oral
Chemical IUPAC Name: 2-[4-[1-hydroxy-4-[4-[hydroxy-di(phenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid
Chemical Formula: C32H39NO4
Fexofenadine on Wikipedia: http://en.wikipedia.org/wiki/Fexofenadine
Organisms Affected: Humans and other mammals