Fexofenadine

1. Drug Name

• Generic Name: Fexofenadine

• Brand Names: Allegra, Telfast, Fastofen, Fexofen, and others

2. Drug Classification

• Class: Antihistamine

• Subclass: Second-generation H1-receptor antagonist

3. Mechanism of Action

• Histamine Blockade: Fexofenadine is a selective peripheral H1 receptor antagonist, which works by blocking histamine, a mediator involved in allergic reactions. By blocking histamine's action at the H1 receptors, fexofenadine reduces symptoms like sneezing, itching, and rhinorrhea (runny nose), common in allergic rhinitis and urticaria.

• Non-Sedating: Fexofenadine does not cross the blood-brain barrier to a significant extent, which minimizes its sedative effects. This makes it a preferred choice for patients who require an antihistamine without sedation or CNS depression.

• Minimal Anti-Cholinergic Effects: Unlike first-generation antihistamines, fexofenadine has negligible anticholinergic effects, reducing side effects like dry mouth and urinary retention.

4. Pharmacokinetics

• Absorption:

  • Bioavailability: Fexofenadine has a bioavailability of about 33%, and its absorption can be affected by the presence of food. It is recommended to take fexofenadine on an empty stomach for optimal absorption.

  • Peak Plasma Concentration: The peak plasma concentration is reached within 2-3 hours after oral administration.

• Distribution:

  • Volume of Distribution (Vd): The Vd of fexofenadine is approximately 5.4 L/kg, indicating its distribution to various tissues in the body.

  • Protein Binding: Fexofenadine is about 60-70% protein-bound, primarily to albumin.

• Metabolism:

  • Fexofenadine undergoes minimal metabolism in the liver. It is not significantly metabolized by cytochrome P450 enzymes, which means it has a low potential for drug-drug interactions via the hepatic CYP system.

• Excretion:

  • Half-life (t½): The elimination half-life of fexofenadine is approximately 14-15 hours, allowing for once or twice-daily dosing.

  • Excretion: Fexofenadine is primarily excreted unchanged in the urine (approximately 80%), with minimal fecal excretion.

• Special Considerations:

  • Renal Impairment: In patients with renal impairment, the clearance of fexofenadine may be reduced, leading to higher plasma levels. Dose adjustments may be needed in such cases.

  • Elderly Patients: In elderly patients, fexofenadine's pharmacokinetics may not differ significantly from younger adults, though careful monitoring in renal impairment is advised.

5. Indications

• Primary Indications:

  • Allergic Rhinitis: Fexofenadine is indicated for the relief of symptoms associated with seasonal and perennial allergic rhinitis, such as sneezing, itchy/watery eyes, and runny nose.

  • Chronic Urticaria: Fexofenadine is used to treat chronic idiopathic urticaria (hives), providing relief from itching and the appearance of hives.

• Off-Label Uses:

  • Angioedema: Fexofenadine may be used off-label for the treatment of angioedema, especially in patients with a history of allergic reactions causing swelling of the skin and mucous membranes.

• Special Populations:

  • Pediatrics: Fexofenadine is approved for use in children aged 6 years and older for allergic rhinitis and chronic urticaria. Dosage adjustments are necessary for children aged 6-11 years.

  • Geriatrics: Generally safe in elderly patients, but dosage adjustments are necessary in those with renal impairment.

6. Dosage and Administration

• Adult Dosing:

  • Allergic Rhinitis:

    • Oral Tablet/Suspension: 60 mg twice daily or 180 mg once daily.

  • Chronic Urticaria:

    • Oral Tablet/Suspension: 180 mg once daily.

• Pediatric Dosing:

  • Allergic Rhinitis:

    • Children aged 6 to 11 years: 30 mg twice daily.

    • Children aged 12 years and older: 60 mg twice daily or 180 mg once daily.

  • Chronic Urticaria:

    • Children aged 6 to 11 years: 30 mg twice daily.

    • Children aged 12 years and older: 180 mg once daily.

• Renal Impairment:

  • In patients with severe renal impairment (CrCl < 30 mL/min), a reduced dose of 60 mg once daily is recommended.

• Administration:

  • Fexofenadine should be taken with water, not fruit juices (especially grapefruit, apple, and orange juices), as these may decrease its absorption.

7. Contraindications

• Absolute Contraindications:

  • Hypersensitivity: Known hypersensitivity to fexofenadine or any of its components.

• Relative Contraindications:

  • Renal Dysfunction: Caution is required in patients with moderate to severe renal impairment, and dose adjustments may be necessary.

  • Pregnancy: Fexofenadine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus (Category C).

8. Warnings and Precautions

• CNS Effects: Fexofenadine is considered non-sedating; however, some patients may still experience mild dizziness or headache. Patients should be warned about the possibility of drowsiness, especially if combined with alcohol or other CNS depressants.

• Renal Dysfunction: Patients with renal impairment may experience higher plasma concentrations of fexofenadine. Renal function should be monitored in such individuals.

• Pregnancy: Fexofenadine is categorized as a Category C drug during pregnancy. It should only be used if absolutely necessary and the benefits outweigh the potential risks.

• Lactation: Fexofenadine is excreted in breast milk in small amounts. Use with caution during breastfeeding.

9. Adverse Effects

• Common Adverse Effects:

  • Headache: A common side effect, usually mild to moderate.

  • Dizziness: Occasional, though typically mild.

  • Dry Mouth: Less common but may occur in some individuals.

• Less Common but Clinically Significant:

  • Fatigue: Fatigue has been reported, especially in patients taking higher doses.

  • Palpitations: Rare, but may occur in some patients.

• Rare/Serious:

  • Severe Allergic Reactions: Anaphylaxis or angioedema is rare but could occur.

  • QT Prolongation: There have been isolated reports of QT interval prolongation with high doses of fexofenadine, especially in patients with predisposing cardiac conditions.

10. Drug Interactions

• CYP450 Inhibitors: Fexofenadine is not significantly metabolized by the cytochrome P450 enzyme system, so it has a low potential for drug-drug interactions.

• Antacids: Aluminum- or magnesium-containing antacids can reduce the absorption of fexofenadine. It is recommended to separate the dosing of fexofenadine and antacids by at least 2 hours.

• Grapefruit, Orange, Apple Juices: These juices can reduce the absorption of fexofenadine and should be avoided.

• Other Antihistamines: Combining fexofenadine with other antihistamines can increase the risk of side effects such as drowsiness and dry mouth.

11. Clinical Pharmacology

• Pharmacodynamics: Fexofenadine selectively blocks the H1 histamine receptor, preventing the activation of histamine and reducing allergic symptoms. Unlike first-generation antihistamines, it has minimal sedative effects because it does not cross the blood-brain barrier effectively.

• Additional Effects: In addition to its antihistaminic effects, fexofenadine has some anti-inflammatory properties, helping to reduce swelling and redness associated with allergic reactions.

12. Special Populations

• Pregnancy: Fexofenadine should only be used during pregnancy if the benefits justify the risks, as there is limited data on its safety in humans.

• Lactation: Fexofenadine is excreted into breast milk in small amounts. Use with caution during breastfeeding.

• Pediatrics: Safe for use in children aged 6 years and older with appropriate dosing adjustments.

• Geriatrics: Elderly patients generally tolerate fexofenadine well, but dose adjustments may be necessary in those with renal impairment.

13. Therapeutic Uses

• Allergic Rhinitis: Fexofenadine is commonly used for symptomatic relief of allergic rhinitis, including seasonal and perennial types.

• Chronic Urticaria: It is an effective treatment for chronic urticaria, providing relief from itching and rash.

14. Monitoring and Follow-Up

• Laboratory Tests: Regular monitoring of renal function is advised, especially in patients with pre-existing renal conditions.

• Symptom Tracking: Patients should track their allergic symptoms (e.g., sneezing, itching) and report any changes to their healthcare provider.

15. Overdose Management

• Symptoms of Overdose: Overdose symptoms may include dizziness, drowsiness, and dry mouth.

• Management: There is no specific antidote for fexofenadine overdose. Management is supportive, and gastric lavage or activated charcoal may be used if overdose occurs within a short time frame.

16. Patient Counseling Information

• Administration: Instruct patients to take fexofenadine once daily, preferably on an empty stomach for optimal absorption.

• Adverse Effects: Patients should be informed about the possibility of mild side effects such as headache or dry mouth.

• Monitoring: Advise patients to report any unusual symptoms such as dizziness or palpitations, particularly when starting therapy.

• Avoid Alcohol: Patients should be advised to avoid alcohol, as it can enhance the sedative effects of the drug.