Fexofenadine – Non-Sedative and Immunomodulatory Antihistamine in the Treatment of Allergic Symptoms

Introduction

First-generation antihistamines are not fully selective for the H₁ receptor and, due to their lipophilicity, they cross the blood-brain barrier. This results in a number of side effects, such as impaired concentration, drowsiness, and sedation, or dryness of the mucous membranes, leading to limitations. Newer molecules are selective ligands for the H₁ receptors, have broader anti-inflammatory effects, and simultaneously have reduced side effects.

Non-Sedative Antihistamines

Newer antihistamines act as inverse agonists and are selective for H₁ receptors. Unlike first generation, they have reduced lipophilicity and therefore penetrate the blood-brain barrier only minimally, influencing a minimum of other receptor systems and thus having a lower risk of central nervous system side effects, including sedative effects. Sufficiently hydrophilic antihistamines are thus referred to as non-sedative antihistamines and are suitable for daytime use. Second-generation non-sedative antihistamines do not sedate even at high doses, allowing for the administration of multiple tablets or higher doses if needed without negatively impacting the patient's alertness.

Anti-Inflammatory Effects of Second-Generation Antihistamines

The effects of second-generation antihistamines are complex and also contribute to the suppression of both bacterial and viral inflammation. This class of substances suppresses the synthesis and release of mediators from mast cells and basophils, inhibits the production of prostaglandins and leukotrienes, inhibits eosinophil migration, and simultaneously reduces the expression of adhesion molecules on the cell surface. These properties are utilized in long-term therapy and prevention of allergic symptoms. One of the representatives of this generation is fexofenadine administered systemically.

Properties of Fexofenadine

Fexofenadine was identified in 1982 as a pharmacologically active metabolite of another antihistamine – terfenadine. Due to the action of cytochrome P450 in the liver, terfenadine is oxidized to the active metabolite fexofenadine, which does not exhibit the pro-arrhythmic effect that led to the withdrawal of the original terfenadine from the market in the 1990s.

Fexofenadine is rapidly absorbed after oral administration, reaching maximum plasma concentration within 1–3 hours, with two-thirds bound to plasma proteins. It is not metabolized in the liver and is excreted mainly via bile, with about 10% of the dose excreted via the kidneys. In patients with renal or liver impairment or in older patients, dose adjustment is usually not necessary.

Indications for Fexofenadine

Fexofenadine is indicated in adults and children aged 12 years and older for the relief of symptoms of seasonal allergic rhinitis at a dose of 120 mg once daily and at a dose of 180 mg once daily for the treatment of chronic idiopathic urticaria.

Clinical studies have shown that the antihistamine effect begins within 1 hour, reaches a peak at 6 hours, and lasts for 24 hours. Studies focusing on seasonal allergic rhinitis have demonstrated that a dose of 120 mg is sufficient to maintain a consistent effect for 24 hours.

The drug is suitable for long-term use, with no tolerance observed even after 28 days of use. Fexofenadine is not cardiotoxic even at high doses, with no significant changes in the QTc interval observed in studied patients or healthy volunteers.

Conclusion

The main advantage of new H₁ antihistamines, such as fexofenadine, is the absence of sedative effects, making them suitable even for patients whose jobs require increased attention and involve driving or operating machinery. New antihistamines are well tolerated and ideal for long-term symptomatic treatment of various allergic conditions, such as urticaria and pollinosis. Second-generation antihistamines also have anti-inflammatory effects in the case of bacterial and viral infections, and some, such as fexofenadine, are associated with enhanced immunomodulatory effects. From January, medicinal products containing fexofenadine in strengths of 120 and 180 mg are newly available in 100-tablet as well as 30-tablet packs.

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Sources: 
1. Doležal M. Overview of H₁ antihistamines for seasonal pollen allergy. Practical Pharmacy 2012; 8 (2): 55–61.
2. Braunová J., Račanský M. Modern antihistamines in allergy treatment – current trends in symptomatic therapy of allergic diseases. Clinical Pharmacology and Pharmacy 2015; 29 (3): 100–104.
3. SPC Ewofex. Available at: www.sukl.cz/modules/medication/detail.php?code=0125863&tab=texts