Is hydroxyzine 25 mg safe to take with Aricept (donepezil)?

Hydroxyzine 25 mg with Donepezil (Aricept): Safety Considerations

Hydroxyzine 25 mg is generally not recommended for concurrent use with donepezil (Aricept) due to the potential for increased anticholinergic effects that could worsen cognition and counteract the benefits of donepezil therapy.

Mechanism of Concern

• Hydroxyzine is a first-generation antihistamine with significant anticholinergic properties that may counteract the cholinergic effects of donepezil, potentially reducing its therapeutic efficacy in treating dementia 1
• Donepezil works by inhibiting acetylcholinesterase to increase acetylcholine levels in the brain, while hydroxyzine has anticholinergic effects that could oppose this mechanism 2
• Sedating antihistamines like hydroxyzine can cause additional cognitive impairment in patients already experiencing cognitive decline 3

Specific Concerns with This Combination

• Hydroxyzine's sedating properties may exacerbate the dizziness that is already a common side effect of donepezil (relative risk 1.47) 3
• The combination may increase the risk of anticholinergic side effects including confusion, blurred vision, dry mouth, and urinary retention 4
• Sleep disturbances are already a concern with donepezil, and hydroxyzine's sedating effects could further complicate sleep patterns 1

Alternative Approaches

• If an antihistamine is needed, consider using a non-sedating, second-generation antihistamine with fewer anticholinergic effects such as cetirizine or loratadine 5
• For anxiety management (if that's the indication for hydroxyzine), consider non-anticholinergic anxiolytics that would have less potential to interfere with donepezil's cognitive benefits 6
• If hydroxyzine is being used for sleep, consider that donepezil is recommended to be taken in the morning rather than at bedtime to minimize sleep disturbances 1

Monitoring Recommendations

• If the combination must be used, monitor closely for:
  • Increased confusion or cognitive decline 4
  • Excessive sedation or dizziness 3
  • Signs of anticholinergic toxicity (dry mouth, blurred vision, urinary retention, constipation) 4
  • Sleep quality and daytime alertness 1

Special Considerations

• The risk of adverse effects may be higher in elderly patients who are more sensitive to both anticholinergic and sedative effects 1
• Patients with advanced dementia may be particularly vulnerable to the cognitive effects of this drug combination 4
• Consider that donepezil already has significant side effects including gastrointestinal symptoms that may be exacerbated by adding another medication 3