Fexofenadine

Fexofenadine is a second-generation antihistamine used for the treatment of various allergic symptoms. Fexofenadine is indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria. Unlike first-generation antihistamines, fexofenadine cannot cross the blood-brain barrier, resulting in fewer central side effects such as sedation.

Fexofenadine is a metabolite of the antihistamine terfenadine, which was marketed as a separate drug due to its favorable properties. It was patented in 1979 and came into medical use in 1996. It is on the World Health Organization's list of essential medicines.

Pharmacodynamics

The H₁-histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen leads to degranulation of mast cells and basophilic granulocytes, which then release histamine and other inflammatory mediators. Histamine subsequently binds to and activates H₁-receptors, leading to further release of pro-inflammatory mediators, such as interleukins. These downstream effects of histamine binding are responsible for a variety of allergic symptoms such as itching, rhinorrhea, and watery eyes.

Fexofenadine has a strong and selective affinity for H₁-receptors and is considered an "inverse agonist" because it binds to and stabilizes the inactive form of the receptor, preventing its activation and subsequent effects. Fexofenadine does not cross the blood-brain barrier and therefore has no significant CNS effects.

Pharmacokinetics

Fexofenadine is rapidly absorbed after oral administration and its absolute bioavailability is approximately 33%. The time to maximum plasma concentration after oral administration is approximately 1-3 hours. Fexofenadine is 60-70% bound to plasma proteins, mainly human serum albumin and alpha-1-acid-glycoprotein. Only 5% of the ingested dose is broken down in the liver. The remaining portion is excreted unchanged from the body, with a majority (approximately 80%) excreted biliarily and the remaining portion excreted in the urine.

Drug Interactions

• Concomitant use of erythromycin or ketoconazole with fexofenadine increases plasma levels of fexofenadine.
• Fexofenadine should not be taken with apples, oranges, or grapefruit juice as they may decrease absorption of the drug. Grapefruit juice may significantly decrease the plasma concentration of fexofenadine.
• Antacids containing aluminum or magnesium should not be taken within 15 minutes of taking fexofenadine as they decrease the absorption of the drug by almost 50%.

Side effects

Possible side effects include:

• Headache
• Back and muscle pain
• Miosis
• Nausea
• Menstrual cramps
• Cough

In rare cases, anxiety and insomnia have also been recorded.