Hydroxyzine (Vistaril, Atarax) is a prescription medication used to treat anxiety, control allergic itching, or act as a sedative before medical procedures. Diphenhydramine (Benadryl) is a widely available over-the-counter option used primarily for allergies, cold symptoms, and as a temporary sleep aid. Since both are commonly employed to manage symptoms like itching or insomnia, understanding the safety profile of their combined use is important.
The Immediate Safety Verdict
Combining hydroxyzine and diphenhydramine is strongly discouraged and generally considered medically unsafe without direct instruction from a healthcare provider. Both medications are potent sedatives, and taking them together substantially increases the risk of severe side effects. This combination should be avoided due to the high potential for a significant drug interaction. This is particularly true for vulnerable individuals, such as the elderly, who are more sensitive to the effects of these drugs.
Pharmacological Basis of the Interaction
The danger of combining these two drugs stems from the fact that they belong to the same pharmacological class: first-generation H1 receptor antagonists. Both hydroxyzine and diphenhydramine work by blocking histamine receptors, and their similar chemical structure allows them to easily cross the blood-brain barrier. This ability to enter the central nervous system (CNS) causes their sedative effects. Taking both medications results in an “additive effect” or “synergistic depression” on the CNS, meaning the combined sedative effect is much greater than either drug alone. Furthermore, both drugs possess anticholinergic properties, blocking acetylcholine receptors, which significantly enhances the risk of adverse reactions when combined.
Symptoms of Combined Use and Overdose
Excessive central nervous system depression can lead to severe drowsiness and sedation, making it difficult to function normally. This impairment often manifests as ataxia, or poor muscle coordination, which significantly increases the risk of accidental falls and injuries. The heightened anticholinergic burden also produces peripheral symptoms, including pronounced dry mouth, blurred vision, difficulty urinating (urinary retention), and constipation. In severe cases, the combination can lead to confusion, disorientation, and anticholinergic delirium, especially in older adults. The most severe outcome is respiratory depression, where breathing slows to dangerously low levels, a risk compounded if other sedatives like alcohol or opioids are present.
Guidelines for Safe Antihistamine Use
Always consult a healthcare provider before starting any new medication, especially when combining prescription and over-the-counter options. If switching between first-generation antihistamines, a brief washout period is advisable to allow the initial drug to clear your system. Hydroxyzine, for example, has a half-life of around 20 hours, meaning its effects can persist into the next day. Patients must completely avoid alcohol and other central nervous system depressants, such as benzodiazepines, while taking either hydroxyzine or diphenhydramine. For those needing relief without heavy sedation, second-generation antihistamines are a safer alternative, as options like cetirizine (Zyrtec) or loratadine (Claritin) have a lower potential for drug interactions.