Recommended Antihistamines with Less Sedation

Fexofenadine, loratadine, and desloratadine (at recommended doses) are the preferred antihistamines with the least sedative properties. 1

Second-Generation vs. First-Generation Antihistamines

Second-generation antihistamines are generally preferred over first-generation antihistamines for allergic rhinitis treatment due to their significantly lower risk of sedation, performance impairment, and anticholinergic effects 1
First-generation antihistamines have substantial potential to cause sedation, performance impairment, and anticholinergic effects, which can be dangerous, particularly in older adults 1
Older adults are especially sensitive to the psychomotor impairment from first-generation antihistamines and face increased risks of complications such as fractures and subdural hematomas from falls 1

Fexofenadine shows no sedative properties at recommended doses and maintains its non-sedating profile even at higher than FDA-approved doses 1, 2
Fexofenadine does not cross the blood-brain barrier according to radiolabeled tissue distribution studies in rats 3
Loratadine and desloratadine do not cause sedation when used at recommended doses 1
Psychomotor and driving tests confirm fexofenadine's non-sedating properties even at very high doses 4

Loratadine and desloratadine may cause sedation when dosed higher than recommended 1
Cetirizine and intranasal azelastine may cause sedation even at recommended doses 1
Cetirizine 10 mg may be associated with mild drowsiness (13.7% vs 6.3% for placebo) 1
Some studies show cetirizine at 10 mg or higher doses can impair performance, though to a much lesser degree than first-generation antihistamines 4, 5

Among the non-sedating antihistamines, no single agent has been conclusively found to achieve superior overall response rates 1, 2
Cetirizine has the fastest onset of action among newer antihistamines, but comes with a higher sedation risk 6
Fexofenadine has a slower onset of action than diphenhydramine and cetirizine but provides similar efficacy without sedation 6
Intranasal antihistamines may be considered for first-line treatment for allergic rhinitis but can cause sedation due to systemic absorption 1

For elderly patients, second-generation antihistamines are strongly preferred due to their reduced risk of falls, cognitive impairment, and anticholinergic effects 1, 2
Patients with low body mass may be more susceptible to sedative effects when given standard doses of even second-generation antihistamines 1
Patients who need to maintain alertness for driving or operating machinery should specifically choose fexofenadine for its documented lack of psychomotor impairment 4, 5

Patients may not be subjectively aware of the impairment caused by antihistamines, even when objective tests demonstrate reduced performance 5
Before prescribing first-generation antihistamines, physicians should ensure patients understand the potential adverse effects and availability of less-sedating alternatives 1
The small cost increase of newer antihistamines ($0.52-2.39 more per dose than diphenhydramine) is generally outweighed by the benefits of reduced sedation 6
Some second-generation antihistamines (not fexofenadine) can have cardiac effects at high doses or with certain drug interactions 7, 8