What is a 3rd generation non-drowsy antihistamine (anti-histamine)?

From the Guidelines

Third-generation non-drowsy antihistamines, such as bilastine, desloratadine, fexofenadine, and levocetirizine, are the preferred treatment options for allergic rhinitis due to their efficacy and minimal sedative effects. These medications work by selectively blocking peripheral H1 receptors without crossing the blood-brain barrier significantly, which explains their minimal sedative effects compared to first-generation antihistamines 1. The typical adult doses are bilastine 20mg once daily, desloratadine 5mg once daily, fexofenadine 180mg once daily (or 60mg twice daily), and levocetirizine 5mg once daily.

Key Characteristics of Third-Generation Antihistamines

• Improved pharmacokinetic properties with longer half-lives allowing once-daily dosing and fewer drug interactions
• Minimal sedative effects, making them suitable for patients who need to maintain alertness for work, driving, or operating machinery
• Effective in treating allergy symptoms, including rhinorrhea, sneezing, and itching associated with allergic rhinitis

Comparison with First-Generation Antihistamines

• First-generation antihistamines, such as diphenhydramine and hydroxyzine, are associated with sedative effects, performance impairment, and anticholinergic effects, making them less desirable for treating allergic rhinitis 1
• Second-generation antihistamines, including third-generation options, are generally preferred over first-generation antihistamines due to their lower risk of adverse effects

Clinical Considerations

• Patients should be aware that full efficacy of third-generation antihistamines may take a few days to develop, and they should be taken regularly rather than as needed
• Potential side effects of third-generation antihistamines include dry mouth, headache, and rarely, heart rhythm disturbances, though these are uncommon at recommended doses
• Older adults and patients with comorbid conditions should be cautious when using antihistamines, and their treatment should be individualized to minimize potential adverse effects 1

From the FDA Drug Label

Desloratadine is a long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Results of a radiolabeled tissue distribution study in rats and a radioligand H1-receptor binding study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier.

Desloratadine is classified as a 3rd generation non-drowsy antihistamine because it does not readily cross the blood brain barrier, which reduces the likelihood of causing drowsiness 2.

From the Research

3rd Generation Non-Drowsy Antihistamines

• The term "3rd generation antihistamines" is not commonly used in the provided studies, but based on the information given, it can be inferred that the newer antihistamines such as desloratadine, fexofenadine, and levocetirizine are considered as part of this group 3.
• These antihistamines were developed to provide therapeutic benefits without the sedative effects associated with first-generation antihistamines, and to avoid the cardiac toxicity associated with some second-generation antihistamines 3.
• Fexofenadine, for example, is the active metabolite of terfenadine, which was withdrawn from the market due to its potential to cause serious arrhythmias 3.

Characteristics of 3rd Generation Antihistamines

• Desloratadine, fexofenadine, and levocetirizine are highly selective for the H1 receptor and have a limited effect on the central nervous system (CNS) 4.
• They have a high affinity for the H1 receptor, with desloratadine having the greatest binding affinity among the three 4.
• These antihistamines do not impair cognitive or psychomotor functioning and are comparable to placebo in terms of somnolence 4.

Efficacy of 3rd Generation Antihistamines

• Desloratadine, fexofenadine, and levocetirizine have been shown to be effective in relieving nasal congestion associated with allergic rhinitis 5.
• They have also been shown to be effective in attenuating the response to nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis 6.
• The three antihistamines have been found to be equally effective in reducing nasal congestion scores and improving symptom scores in patients with allergic rhinitis 5, 6.