Fexofenadine

• Second-Generation H1 Antihistamine
• Selective peripheral H1 receptor inverse agonist
• Active metabolite of terfenadine

Parent class: Histamine & Antihistamines

Fexofenadine selectively blocks peripheral H1 receptors.

Effects:

• ↓ Histamine-mediated vasodilation
• ↓ Capillary permeability
• ↓ Pruritus
• ↓ Sneezing and rhinorrhea

Key Feature:

• Minimal penetration of the blood-brain barrier
• Essentially non-sedating at therapeutic doses

Fexofenadine is the active metabolite of terfenadine.

Terfenadine was removed from the market due to QT prolongation and torsades risk (CYP3A4 inhibition interactions).

Fexofenadine:

• Does not significantly prolong QT interval
• Does not rely on hepatic metabolism for activation

• Oral administration
• Onset: ~1 hour
• Duration: ~24 hours
• Primarily eliminated unchanged in feces and urine
• Minimal hepatic metabolism

Absorption reduced by:

• Aluminum/magnesium antacids
• Fruit juices (apple, orange, grapefruit)

Separate dosing from antacids by at least 2 hours.

• Allergic Rhinitis
• Chronic idiopathic urticaria
• Seasonal allergies

Effective for:

• Sneezing
• Itching
• Rhinorrhea

Less effective for:

• Nasal congestion (intranasal steroids preferred)

• 60 mg PO twice daily
• OR 180 mg PO once daily

Dose adjustment in renal impairment.

Generally very well tolerated.

Possible:

• Headache
• Mild nausea
• Rare dizziness

Sedation:

• Minimal to none
• Lowest sedation risk among common 2nd-generation H1 blockers

• Renal impairment (dose adjust)
• Hypersensitivity

Caution:

• Avoid coadministration with fruit juice
• Separate from antacids

• Aluminum/magnesium antacids ↓ absorption
• Fruit juice ↓ bioavailability
• Minimal CYP interaction
• No meaningful QT risk at therapeutic doses

• Least sedating of the second-generation H1 blockers.
• Preferred in patients requiring full daytime alertness.
• Safe cardiovascular profile compared to its predecessor (terfenadine).
• Does not significantly impair cognition or psychomotor function.
• Not effective for nasal congestion as monotherapy.

• Histamine & Antihistamines
• Loratadine
• Cetirizine
• Allergic Rhinitis – Stepwise Therapy