Indications
In the United States, fexofenadine is indicated for the symptomatic treatment of allergic rhinitis in patients aged 2 years and older, as well as chronic idiopathic urticaria in patients aged 6 months and older. Additionally, in Canada, the same indications apply, although it is approved for patients aged 12 years and older. Fexofenadine is also available in combination with pseudoephedrine, specifically for the treatment of seasonal allergic rhinitis in individuals aged 12 years and older.
Pharmacodynamics
Fexofenadine functions by antagonizing the actions of histamine, an endogenous compound largely responsible for allergic symptoms. Its efficacy in alleviating allergy symptoms stems from this mechanism. The drug's relatively long duration of action, approximately 24 hours, allows for convenient once or twice-daily dosing. Rapid absorption facilitates an onset of action within 1 to 3 hours. It's important to note that fexofenadine should not be consumed with fruit juice, as this may hinder its absorption.
Absorption
Upon oral administration, fexofenadine is rapidly absorbed, with an absolute bioavailability of approximately 33%. Following ingestion, the time to reach maximum plasma concentration (Tmax) is approximately 1 to 3 hours. At steady state, twice-daily dosing of 60 mg yields an AUCss(0-12h) of 1367 ng/mL.h and a Cmax of 299 ng/mL. The presence of fruit juices, such as apple, orange, or grapefruit, can decrease fexofenadine's AUC by more than 20% due to inhibition of OATP transporters, leading to recommendations for administration with water only. Similarly, a high-fat meal can diminish the AUC and Cmax by over 20%.
Metabolism
Fexofenadine undergoes minimal hepatic metabolism, with only 5% of an ingested dose being metabolized. The primary metabolites identified include a methyl ester of fexofenadine, comprising 3.6% of the total dose, and MDL 4829, accounting for 1.5% of the total dose. The specific enzymes responsible for this metabolic process have not been clearly identified.
Mechanism of Action
Fexofenadine functions primarily as an inverse agonist of the H1 histamine receptor, a key player in mediating hypersensitivity and allergic responses. Upon encountering allergens, mast cells and basophils undergo degranulation, releasing histamine and other inflammatory substances. This histamine then binds to H1 receptors, triggering further secretion of pro-inflammatory cytokines such as interleukins from these immune cells, which leads to common allergic symptoms including itching, runny nose, and watery eyes. Fexofenadine binds to and stabilizes the inactive form of the H1 receptor, thereby preventing its activation and the cascade of inflammatory events that follow. This compound demonstrates strong and selective affinity for H1 receptors and lacks antidopaminergic, antiserotonergic, anticholinergic, sedative, or adrenergic blocking activities. Additionally, fexofenadine does not penetrate the blood-brain barrier, minimizing the risk of central nervous system side effects.
