Fexofenadine: Uses, Interactions, Mechanism of Action | DrugBank Online

Fexofenadine relieves allergy symptoms by antagonizing the actions of histamine, an endogenous compound predominantly responsible for allergic symptomatology.10 The relatively long duration of action of fexofenadine (approximately 24 hours)7 allows for once or twice daily dosing, and its rapid absorption allows for an onset of action within 1-3 hours. Fexofenadine should not be taken with fruit juice, as this may impair its absorption.10

The H1 histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H1 receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.7

Fexofenadine is considered an “inverse agonist” of the H1 receptor because it binds to and stabilizes the inactive form of the receptor, preventing its activation and subsequent downstream effects.7 It has a potent and selective affinity for H1 receptors, and there is no evidence that it carries antidopaminergic, antiserotonergic, anticholinergic, sedative, or adrenergic blocking activity.9 Fexofenadine does not cross the blood-brain barrier and thus is unlikely to cause significant CNS effects.9

TargetActionsOrganism

A

Histamine H1 receptor

antagonist

Humans

Fexofenadine is rapidly absorbed following oral administration and its absolute bioavailability is approximately 33%.9 The Tmax following oral administration is approximately 1-3 hours.9,7 The steady-state AUCss(0-12h) and Cmax following twice daily dosing of 60mg are 1367 ng/mL.h and 299 ng/mL, respectively.9

Fexofenadine AUC is decreased by >20% when coadministered with fruit juices (e.g. apple, orange, grapefruit) due to their inhibition of OATP transporters – for this reason, prescribing information recommends administering fexofenadine only with water.8 Similarly, coadministration of fexofenadine with a high-fat meal appears to decrease AUC and Cmax by >20%.10

The volume of distribution is approximately 5.4-5.8 L/kg.7

Fexofenadine is 60-70% bound to plasma proteins,10 primarily to albumin and α1-acid glycoprotein. The extent of protein binding is decreased to 56-68% and 56-75% in patients with renal and hepatic impairment, respectively.9

Fexofenadine is very minimally metabolized, with only 5% of an ingested dose undergoing hepatic metabolism.10,7 The only identified metabolites are a methyl ester of fexofenadine (3.6% of the total dose) and MDL 4829 (1.5% of the total dose).9 The enzymes responsible for this metabolism have not been elucidated.

Hover over products below to view reaction partners

• Fexofenadine

  • MDL 4829 (Azacyclonol)

Approximately 80% of an ingested dose is eliminated in the feces, likely largely unchanged due to fexofenadine’s limited metabolism, and 11% is eliminated in the urine.7 The principal pathways of fexofenadine elimination are biliary and renal.9

The terminal elimination half-life is approximately 11-15 hours.9,7

The oral clearance of fexofenadine is approximately 50.6 L/h and the renal clearance is approximately 4.32 L/h.9

No deaths were observed following the oral administration of up to 5000 mg/kg in both mice and rats (equivalent to approximately 100-200x the recommended human dose). Single doses of up to 800 mg and chronic exposure of up to 690 mg twice daily for 1 month in humans did not result in clinically significant adverse events. Symptoms of overdosage are consistent with fexofenadine’s adverse effect profile and are likely to include dizziness, drowsiness, and dry mouth.10

If overdosage occurs, employ symptomatic and supportive treatment. Hemodialysis does not effectively remove fexofenadine from the blood and is therefore of no benefit.10

Not Available