Fexofenadine

Fexofenadine is a selective peripheral H1 receptor antagonist. It blocks the action of histamine at H1 receptors, reducing symptoms such as sneezing, itching, and rhinorrhea. Unlike first-generation antihistamines, it does not readily cross the blood-brain barrier, minimizing sedation.¹

The drug is rapidly absorbed after oral administration, with peak plasma concentrations reached in 2–3 hours. It is primarily excreted unchanged in feces and urine, with a half-life of about 14–15 hours. Fexofenadine is a substrate of P-glycoprotein, and its absorption can be affected by fruit juices such as grapefruit, orange, and apple, which reduce its bioavailability.

Fexofenadine is indicated for the relief of symptoms associated with seasonal allergic rhinitis and for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. It is effective in reducing nasal congestion, sneezing, and itchy, watery eyes.²

Clinical trials have demonstrated that fexofenadine is as effective as other second-generation antihistamines, such as loratadine and cetirizine, but with a lower incidence of sedation. It is available in oral tablets and orally disintegrating tablets, with doses ranging from 30 mg to 180 mg daily depending on age and condition.³

Fexofenadine is generally well tolerated, with the most common adverse effects being headache, dizziness, and nausea. Unlike terfenadine, it does not prolong the QT interval, making it safer for patients with cardiac conditions.

Drug interactions are limited but include an increased risk of side effects when taken with ketoconazole or erythromycin, which may increase fexofenadine plasma levels. It is classified as pregnancy category C in the US, and caution is advised during breastfeeding.⁴

Fexofenadine was developed as a metabolite of terfenadine, which was withdrawn from the market due to rare but serious cardiac arrhythmias. The discovery that terfenadine's active metabolite retained antihistaminic activity without cardiotoxicity led to fexofenadine's approval in 1996.⁵

Fexofenadine is also used off-label for the treatment of eosinophilic esophagitis, though evidence is limited. Its absorption is influenced by food intake; high-fat meals can reduce its bioavailability. Additionally, fexofenadine has been studied for potential anti-inflammatory effects beyond histamine antagonism, including inhibition of mast cell degranulation.⁶

H1 receptor

A histamine receptor subtype that mediates allergic responses.

P-glycoprotein

A membrane transporter that pumps drugs out of cells, affecting absorption.

QT interval

A measure of heart electrical activity; prolongation can lead to arrhythmias.