Fexofenadine: Non-Sedating Second-Generation Antihistamine
Fexofenadine (Telfast, Allegra) is a second-generation H1 antihistamine, the active metabolite of terfenadine. It does not cross the blood-brain barrier and does not inhibit hERG potassium channels — making it non-sedating and free of the cardiac risk of its predecessor.
First-line treatment for seasonal allergic rhinitis and chronic idiopathic urticaria. Among the most extensively used antihistamines worldwide due to its excellent safety profile.
Mechanism of Action
Selective inverse agonist at H1 histamine receptors. Does not penetrate the CNS significantly (P-glycoprotein substrate), explaining the absence of sedation. Does not block cardiac hERG potassium channels — no QT prolongation risk.
Indications & Use
Seasonal allergic rhinitis (hayfever), chronic idiopathic/spontaneous urticaria (CIU/CSU). Not indicated for acute anaphylaxis (epinephrine required). Age ≥2 years approved.
Dosage
Adults and children ≥12 years: 120 mg once daily (rhinitis) or 180 mg once daily (urticaria). Children 6–11 years: 30 mg twice daily. Children 2–5 years: 15 mg twice daily. Reduce dose in renal impairment.
Side Effects
Excellent tolerability. Headache (most common). Nausea, dizziness — uncommon. No clinically relevant sedation (no impairment of driving ability at therapeutic doses). No anticholinergic effects.
Drug Interactions
Grapefruit juice, apple juice, orange juice: significantly reduce fexofenadine bioavailability (OATP1A2 inhibition in gut) — avoid with fruit juice (take with water). Antacids (Al/Mg hydroxide): reduce absorption — take 2 hours apart. Erythromycin and ketoconazole: increase fexofenadine levels (not clinically significant).
Contraindications
Hypersensitivity to fexofenadine. Caution in severe renal impairment (dose adjustment). Generally safe in pregnancy (category C) — preferred over first-generation antihistamines.
Frequently Asked Questions
Does fexofenadine cause drowsiness?
No. Fexofenadine does not cross the blood-brain barrier significantly (it is a substrate of P-glycoprotein). Clinical trials show no difference from placebo in sedation and no impairment of driving ability, making it ideal for patients who need to drive or operate machinery.
Why should fexofenadine not be taken with fruit juice?
Grapefruit, apple, and orange juice reduce fexofenadine absorption by up to 36-47% by inhibiting OATP1A2 transporters in the gut. Always take fexofenadine with water, not fruit juice.
Is fexofenadine better than cetirizine?
Both are second-generation antihistamines. Fexofenadine is completely non-sedating (cetirizine causes mild sedation in some patients). Cetirizine is cheaper and also available OTC. For patients who experience drowsiness with cetirizine, fexofenadine is preferred.
References
- EMA Telfast SPC 2023
- BSACI Guideline Allergic Rhinitis 2022
- Simons FE. NEJM 2004
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.