From the Guidelines
It is strongly advised against taking Benadryl (diphenhydramine) and hydroxyzine together due to the increased risk of adverse effects, particularly sedation and anticholinergic effects, as highlighted in the study published in the Journal of Allergy and Clinical Immunology 1.
Key Considerations
- Both Benadryl and hydroxyzine are first-generation antihistamines that can cause significant sedation, performance impairment, and anticholinergic effects, as noted in the study 1.
- The combination of these two medications can lead to enhanced sedation, excessive drowsiness, dry mouth, blurred vision, urinary retention, and confusion, which is particularly concerning for elderly patients who are more susceptible to these effects.
- The use of first-generation antihistamines like hydroxyzine has been associated with impaired learning and school performance in children, as well as driving impairment in adults, as reported in the study 1.
- Concomitant use of other CNS-active substances, such as alcohol, sedatives, hypnotics, or antidepressant medication, may further enhance performance impairment from antihistamines, as warned in the study 1.
Alternative Approaches
- Second-generation antihistamines are generally preferred over first-generation antihistamines for the treatment of allergic rhinitis due to their lower likelihood of adverse effects, as recommended in the study 1.
- If considering taking these medications together, it is essential to consult with a healthcare provider first to discuss symptoms and determine the most appropriate treatment option, which may include using just one of these medications or suggesting an alternative approach to manage the condition more effectively and safely.
From the FDA Drug Label
THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS Patients should also be advised against the simultaneous use of other CNS depressant drugs, and cautioned that the effects of alcohol may be increased
Benadryl and hydroxyzine should not be given together because both are central nervous system depressants, and their combined use may increase the risk of adverse effects such as drowsiness, confusion, and over sedation 2.
From the Research
Antihistamine Interactions
- The interaction between Benadryl (diphenhydramine) and hydroxyzine is not directly addressed in the provided studies, but both are first-generation antihistamines known for their sedative effects 3, 4, 5, 6.
- First-generation antihistamines, such as diphenhydramine and hydroxyzine, can have adverse effects on the central nervous system, including sedation and impairment of cognitive function 3, 4.
- The use of multiple first-generation antihistamines together may increase the risk of adverse effects, particularly sedation and cognitive impairment 4, 5, 6.
Safety and Efficacy
- Newer, second- and third-generation antihistamines are considered safer and more effective for the treatment of allergic reactions, with less sedation and fewer adverse effects compared to first-generation antihistamines 3, 4, 7.
- The Canadian Society of Allergy Clinical Immunology recommends the use of newer generation antihistamines as the first-line treatment for allergic rhinitis and urticaria, due to their improved safety profile 4.
Specific Antihistamines
- Diphenhydramine (Benadryl) is a first-generation antihistamine that can impair psychomotor performance and cognitive function, and has a higher incidence of sedation compared to newer antihistamines 3, 6.
- Hydroxyzine is also a first-generation antihistamine, and its use has been associated with significant side effects, including sedation and anticholinergic effects 5, 6.
- Cetirizine, a second-generation antihistamine, is characterized by its high selectivity for the H1 receptor site, reliable inhibition of histamine-induced allergic reactions, and low incidence of sedation and anticholinergic side effects 7.