Fexofenadine - Drug Monograph

Introduction

Fexofenadine is a second-generation, non-sedating antihistamine medication that belongs to the piperidine class. It is a selective peripheral H1-receptor antagonist developed as the active metabolite of terfenadine. Unlike first-generation antihistamines, fexofenadine demonstrates minimal penetration of the blood-brain barrier, resulting in significantly reduced sedative effects while maintaining potent antihistaminic activity.

Mechanism of Action

Fexofenadine competitively inhibits histamine binding at H1-receptors in the gastrointestinal tract, blood vessels, and respiratory smooth muscle. This blockade prevents histamine-mediated allergic responses including vasodilation, increased vascular permeability, smooth muscle contraction, and sensory nerve stimulation. The drug exhibits high specificity for peripheral H1-receptors with minimal affinity for muscarinic, adrenergic, or serotonin receptors.

Indications

• Seasonal allergic rhinitis (hay fever) in adults and children ≥2 years
• Chronic idiopathic urticaria in adults and children ≥6 months
• Off-label uses may include other allergic conditions under specialist supervision

Dosage and Administration

• Allergic rhinitis: 60 mg twice daily or 180 mg once daily
• Chronic urticaria: 60 mg twice daily or 180 mg once daily

• Children 6 months to <2 years: 15 mg twice daily (urticaria only)
• Children 2-11 years: 30 mg twice daily

• Renal impairment (CrCl <80 mL/min): Reduce dose by 50%
• Hepatic impairment: No dosage adjustment required
• Geriatric patients: Consider renal function assessment
• Administration: Take on empty stomach (1 hour before or 2 hours after meals)

Pharmacokinetics

• Absorption: Rapid but variable (30-40% bioavailability), significantly reduced by high-fat meals or fruit juices
• Distribution: Volume of distribution ~5.4-5.8 L/kg, 60-70% protein bound
• Metabolism: Minimal hepatic metabolism (<5%), no active metabolites
• Elimination: Primarily excreted unchanged in feces (80%) and urine (11%), half-life ~14 hours
• Onset: 1-3 hours, duration 24 hours

Contraindications

• Hypersensitivity to fexofenadine or any component of the formulation
• Concomitant use with aluminum/magnesium-containing antacids (within 15 minutes)
• Severe renal impairment without appropriate dose adjustment

Warnings and Precautions

• Use caution in patients with renal impairment (dose adjustment required)
• Pregnancy Category C: Use only if potential benefit justifies potential risk
• Lactation: Excreted in breast milk; use with caution
• Not recommended for children under 6 months
• May mask symptoms of ototoxicity from other medications

Drug Interactions

• Antacids containing aluminum/magnesium: Decrease fexofenadine absorption (separate administration by 2 hours)
• Erythromycin, ketoconazole: May increase fexofenadine concentrations
• Fruit juices (apple, orange, grapefruit): Decrease absorption by inhibiting OATP transporters
• P-glycoprotein inhibitors: May increase fexofenadine levels

Adverse Effects

• Headache (10.6%)
• Dizziness (1.5%)
• Nausea (1.5%)
• Fatigue (1.3%)
• Dyspepsia

• Hypersensitivity reactions (angioedema, rash, pruritus)
• Tachycardia
• Seizures (case reports)

Monitoring Parameters

• Efficacy assessment: Symptom relief in allergic conditions
• Renal function in patients with pre-existing renal impairment
• Adverse effects: Particularly in elderly patients
• Drug interactions: With concomitant medications
• Pediatric growth monitoring during long-term use

Patient Education

• Take medication on empty stomach for optimal absorption
• Avoid concurrent use with antacids or fruit juices
• Report any signs of allergic reaction (rash, swelling, difficulty breathing)
• May be taken without regard to timing of antihistamine dose
• Does not typically cause drowsiness, but use caution when driving until effects known
• Store at room temperature, protected from moisture
• Seek medical attention if symptoms worsen or persist beyond 1 week

References

1. Simpson K, Jarvis B. Fexofenadine: A Review of its Use in the Management of Seasonal Allergic Rhinitis and Chronic Idiopathic Urticaria. Drugs. 2000;59(2):301-321. 2. FDA Prescribing Information: Allegra (fexofenadine hydrochloride). 2021. 3. Meltzer EO. The role of fexofenadine in the treatment of allergic rhinitis and chronic idiopathic urticaria. Expert Opin Pharmacother. 2011;12(1):93-107. 4. Russell T, Stoltz M, Weir S. Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers. Clin Pharmacol Ther. 1998;64(6):612-621. 5. Bernstein JA. H1-Antihistamines in the Management of Allergic Rhinitis and Chronic Urticaria. Immunol Allergy Clin North Am. 2017;37(2):305-319. 6. Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004;351(21):2203-2217.