Most Common Side Effects of Hydroxyzine
The most common side effects of hydroxyzine are drowsiness/sedation (occurring in approximately 80% of patients), dry mouth, and performance impairment, with these effects typically being mild and transitory but potentially persisting longer than expected due to prolonged metabolite half-lives. 1, 2, 3
Central Nervous System Effects (Most Frequent)
Drowsiness and Sedation:
- Sedation occurs in approximately 80% of patients taking hydroxyzine, which is notably higher than diphenhydramine (50%) and promethazine (60-73%) 2
- Drowsiness is usually transitory and may disappear within a few days of continued therapy or upon dose reduction 3
- Critical caveat: Performance impairment can exist without subjective awareness of sedation—patients may feel alert while experiencing significant cognitive deficits 1
- Even bedtime-only dosing causes significant daytime drowsiness, decreased alertness, and performance impairment the following day 1
- Performance impairment persists longer than plasma levels of the parent compound due to prolonged half-lives of hydroxyzine and its metabolites 1
Cognitive and Motor Impairment:
- Impaired work performance, reduced productivity, and increased risk of occupational accidents 1
- Drivers taking hydroxyzine were 1.5 times more likely to be responsible for fatal automobile accidents 1
- Impaired driving performance worsens significantly with concurrent cell phone use 1
- Impaired learning and school performance in children 1
Less Common CNS Effects:
- Headache (post-marketing reports) 3
- Involuntary motor activity including rare instances of tremor and convulsions, usually with doses considerably higher than recommended 3
- Paradoxical CNS stimulation, particularly in children 1
- Hallucinations (post-marketing reports) 3
Anticholinergic Effects (Common)
Dry Mouth:
- This is the most frequently reported anticholinergic side effect 3
Other Anticholinergic Effects:
- Dry eyes 1
- Constipation 1
- Inhibition of micturition (urinary retention) 1
- Increased risk for provocation of narrow-angle glaucoma 1
Cardiac Effects (Rare but Serious)
- QT prolongation and Torsade de Pointes reported in post-marketing experience 3
- Clinically significant respiratory depression has not been reported at recommended doses 3
Dermatologic Effects (Rare)
- Acute Generalized Exanthematous Pustulosis (AGEP) 3
- Fixed drug eruptions 3
- Pruritus, rash, urticaria (post-marketing reports) 3
Special Population Considerations
Elderly Patients:
- Older adults are more sensitive to psychomotor impairment from hydroxyzine 1, 2
- Increased risk for falls, fractures, and anticholinergic complications 1
- Lower dosages should be considered due to increased risk of sedative effects 2
Pregnant Women and Neonates:
- Hydroxyzine is contraindicated during early pregnancy 1, 2
- Neonatal withdrawal symptoms can occur with maternal use, including tremors, irritability, hyperactivity, jitteriness, shrill cry, myoclonic jerks, hypotona, increased respiratory and heart rates, feeding problems, and clonic movements 1
- Withdrawal symptoms may last up to 5 weeks with treatment 1
Patients with Renal/Hepatic Impairment:
- Dose should be halved in moderate renal impairment and avoided in severe renal impairment 1, 2
- Should be avoided in severe liver disease due to inappropriate sedating effects 1, 2
Drug Interaction Enhancement
- Concomitant use with other CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) further enhances performance impairment 1, 2
Important Clinical Context
Hydroxyzine differs from diphenhydramine: Recent toxicology data shows hydroxyzine-poisoned patients are less likely to develop antimuscarinic findings than diphenhydramine-poisoned patients and more likely to have mild CNS depression than an antimuscarinic toxidrome 4. This means clinicians should not generalize the illness script of diphenhydramine exposures to hydroxyzine exposures 4.