Fexofenadine is a second-generation, non-sedating H1 antihistamine that is widely used for the symptomatic treatment of seasonal allergic rhinitis, chronic idiopathic urticaria, and other allergic conditions. It is an active metabolite of terfenadine, developed specifically to avoid the cardiac toxicity and drug interaction issues associated with its predecessor. Its non-sedating profile and minimal central nervous system (CNS) penetration make it preferable in patients requiring daytime symptom relief without drowsiness.
Pharmacological Classification
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Therapeutic Class: Antiallergic, antihistamine
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Pharmacologic Class: Second-generation selective H1 receptor antagonist
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ATC Code: R06AX26
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Available Forms:
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Oral tablets: 30 mg, 60 mg, 120 mg, 180 mg
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Oral suspension (not available in all markets): 30 mg/5 mL
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Mechanism of Action
Fexofenadine selectively antagonizes peripheral H1 receptors on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. When histamine is released during an allergic reaction, it binds to H1 receptors and causes vasodilation, increased vascular permeability, and sensory nerve stimulation (leading to symptoms such as sneezing, rhinorrhea, and itching).
Fexofenadine blocks these receptors, thereby:
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Reducing nasal congestion, sneezing, itchy eyes, and rashes
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Preventing histamine-mediated symptoms without sedative effects because it does not cross the blood-brain barrier significantly
Therapeutic Indications
Licensed Uses
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Seasonal Allergic Rhinitis (SAR) (hay fever):Relief of symptoms such as nasal discharge, sneezing, itchy nose/palate, and ocular symptoms
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Chronic Idiopathic Urticaria (CIU):Control of pruritus, wheals, and angioedema
Off-Label Uses (under supervision)
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Atopic dermatitis (adjunctive)
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Cold urticaria
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Allergic conjunctivitis (if systemic treatment needed)
Dosage and Administration
Adults and Adolescents (≥12 years)
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Seasonal Allergic Rhinitis:120 mg once daily (preferred)180 mg once daily may also be used but not officially licensed for SAR in all countries
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Chronic Idiopathic Urticaria:180 mg once daily
Children (6–11 years)
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30 mg twice daily
Children (2–5 years)
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Suspension (30 mg/5 mL) at 15 mg twice daily, if available and approved
Renal Impairment
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Use with caution; dose reduction may be advisable
Hepatic Impairment
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No specific adjustment required, but caution recommended
Pharmacokinetics
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Absorption: Rapid, peak plasma concentration in 1–3 hours
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Bioavailability: Moderate (~33%)
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Protein Binding: 60–70%
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Metabolism: Minimal hepatic metabolism; does not undergo significant CYP450 transformation
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Half-life: ~14 hours (prolonged in renal impairment)
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Excretion: Primarily feces (via biliary excretion), ~10% unchanged in urine
Contraindications
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Hypersensitivity to fexofenadine or any component of the formulation
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Severe renal insufficiency (relative contraindication for high doses)
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Avoid use with fruit juices (e.g., orange, apple, grapefruit) as they reduce drug absorption via OATP inhibition in the gut
Warnings and Precautions
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Although fexofenadine has minimal sedating effects, very sensitive individuals may experience drowsiness
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In patients with cardiac disease, monitor for QT prolongation (rare)
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In elderly or renally impaired individuals, start at the lowest effective dose
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Avoid antacids containing aluminum or magnesium within 2 hours of taking the medication (they reduce absorption)
Adverse Effects
Common (1–10%)
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Headache
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Drowsiness (less than first-generation antihistamines)
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Dizziness
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Nausea
Uncommon (<1%)
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Fatigue
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Insomnia
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Dry mouth
Rare
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Hypersensitivity reactions (urticaria, rash, angioedema, anaphylaxis)
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Palpitations or tachycardia
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Dyspnea
Drug Interactions
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Fruit juices: Orange, grapefruit, and apple juices reduce fexofenadine absorption (by up to 70%) by inhibiting intestinal OATP transporters. Administer with water only.
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Aluminum and magnesium-containing antacids: Reduce fexofenadine bioavailability; separate administration by ≥2 hours
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Ketoconazole and erythromycin: Increase plasma levels of fexofenadine by inhibiting P-glycoprotein transporters, though without clinical significance
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Alcohol and CNS depressants: Although fexofenadine is non-sedating, caution advised when combined
Comparison with Other Antihistamines
Unlike first-generation antihistamines (e.g., chlorphenamine, diphenhydramine), fexofenadine:
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Does not readily cross the blood-brain barrier
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Causes minimal sedation and impaired psychomotor function
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Is long-acting, allowing once-daily dosing
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Is less anticholinergic, avoiding dry mouth, constipation, urinary retention
Compared with loratadine, cetirizine, or desloratadine:
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Fexofenadine is less sedating than cetirizine
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Faster onset of action than loratadine in some studies
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Similar efficacy to desloratadine but possibly better tolerated
Pregnancy and Lactation
Pregnancy
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Category B (FDA) / UK: Use only if clearly needed
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No adequate human studies; animal studies show no fetal harm
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Generally considered safe when benefit outweighs risk
Lactation
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Low levels detected in breast milk; use with caution
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Prefer non-sedating antihistamines like loratadine or cetirizine if needed during breastfeeding
Use in Special Populations
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Elderly: No specific dose adjustment, but use lowest effective dose
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Hepatic impairment: No adjustment required
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Renal impairment: May require dose reduction; monitor for side effects
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Children: Safe and effective above 6 years (or 2 years for urticaria depending on formulation)
Patient Counseling Points
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Take with water only, not fruit juice
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Can be taken with or without food
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Avoid antacids 2 hours before or after
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Effects are not immediate in all patients – may take several hours
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Continue use throughout pollen season if prescribed for hay fever
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If dizziness or drowsiness occurs, avoid driving or operating machinery
Brand Names
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Allegra® (USA)
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Telfast® (UK and EU)
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Fastofen®, Fexigra®, Xergic – Generic alternatives
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Available as OTC and prescription depending on country
Storage
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Store at room temperature (15–30°C)
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Protect from excessive moisture
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Keep tablets in original blister packaging to preserve stability
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