Second Generation Antihistamines: Uses, Doses, Safety and Clinical Tips

Second Generation Antihistamines

Practical Guide for Clinicians and Patients

Allergic rhinitis and chronic urticaria affect up to 20 to 30 percent of the population in India. Many patients still receive sedating antihistamines. You can improve symptom control and safety by choosing second generation agents.

What are second generation antihistamines

These drugs selectively block peripheral H1 receptors. They reduce histamine driven symptoms without significant central nervous system penetration.

Common examples

Cetirizine 

Levocetirizine 

Fexofenadine 

Loratadine 

Desloratadine 

Bilastine 

Rupatadine 

How they work

Histamine released from mast cells binds to H1 receptors. This causes itching, sneezing, rhinorrhea, conjunctival redness, and wheals. H1 blockers prevent this response.

Most agents act within 1 hour. Duration is about 24 hours. Once daily dosing improves adherence.

Clinical indications

Use them in:

Allergic rhinitis, 

Chronic spontaneous urticaria, 

Allergic conjunctivitis,

Insect bite reactions.

For allergic rhinitis, combine with an intranasal corticosteroid for moderate to severe disease. Intranasal steroids reduce nasal congestion better than antihistamines alone.

Sedation profile

Second generation drugs cause less sedation than first generation agents such as diphenhydramine or chlorpheniramine.

Sedation risk varies:

Cetirizine and levocetirizine cause mild drowsiness in up to 10 to 15 percent of users Fexofenadine and bilastine show minimal sedation in clinical trials 

Advise patients who drive or operate machinery to choose low sedation options.

Dosing in adults

Cetirizine 10 mg once daily 

Levocetirizine 5 mg once daily 

Fexofenadine 120 or 180 mg once daily 

Loratadine 10 mg once daily 

Desloratadine 5 mg once daily 

Bilastine 20 mg once daily 

Rupatadine 10 mg once daily 

Chronic urticaria management

Start with standard dosing.

If symptoms persist, increase dose up to four times the standard dose, as recommended by international urticaria guidelines.

Example:

Fexofenadine 180 mg once daily can be increased to 180 mg twice daily or higher under supervision.

Avoid combining multiple antihistamines. Increase the dose of one agent instead.

Drug interactions and practical points

Fexofenadine absorption reduces with apple, orange, and grapefruit juice. Advise patients to take with water Bilastine absorption reduces with food. Give on empty stomach Rupatadine interacts with strong CYP3A4 inhibitors such as certain azoles and macrolides 

Pregnancy and lactation

Loratadine and cetirizine have the best safety data in pregnancy.

During breastfeeding, cetirizine, loratadine, and fexofenadine are preferred due to low milk transfer and minimal infant sedation risk.

Pediatric use

Cetirizine from 6 months Loratadine from 2 years Fexofenadine from 6 years 

Always adjust dose by age and weight.

Elderly considerations

Avoid first generation antihistamines in older adults. They increase risk of confusion, urinary retention, constipation, and falls. Second generation agents are safer.

Key counseling points

Tell patients to:

Take once daily at the same time Avoid alcohol if using cetirizine or levocetirizine Continue daily use in chronic urticaria instead of taking only when itching starts Seek review if symptoms persist beyond 2 to 4 weeks 

Take home message

Second generation antihistamines offer effective symptom control with low sedation and better safety.

Choose the right agent. Use correct dosing. Escalate appropriately in chronic urticaria.

This improves outcomes and reduces unnecessary adverse effects.