Side Effects of Hydroxyzine
Hydroxyzine causes significant sedation, performance impairment, and anticholinergic effects that can persist into the next day even with bedtime dosing, making second-generation antihistamines generally preferred for most clinical situations. 1
Central Nervous System Effects
Sedation and Performance Impairment
- Drowsiness and performance impairment occur in many patients and can exist without subjective awareness of sedation, meaning patients may feel alert while still experiencing cognitive deficits 1
- Drivers responsible for fatal automobile accidents were 1.5 times more likely to be taking first-generation antihistamines like hydroxyzine compared to drivers not responsible for accidents 1, 2
- Impaired driving performance with hydroxyzine worsens significantly with concurrent cell phone use 1, 2
- Workers taking hydroxyzine exhibit impaired work performance, reduced productivity, and increased risk of occupational accidents 1
- Performance impairment persists longer than plasma levels of the parent compound due to prolonged half-lives of hydroxyzine and its metabolites 1
- Even bedtime-only dosing causes significant daytime drowsiness, decreased alertness, and performance impairment the following day 1, 2
Cognitive and Neurological Effects
- Impaired learning and school performance in children 1
- Involuntary motor activity, including rare instances of tremor and convulsions (usually at doses considerably higher than recommended) 3
- Headache 3
- Hallucinations 3
- Paradoxical CNS stimulation may occur, particularly in children 1
Sleep Architecture Changes
- Hydroxyzine can alter sleep architecture and potentially trigger nightmares, particularly with bedtime dosing, by affecting serotonin, norepinephrine, dopamine, GABA, and acetylcholine 4
- Disturbed dreaming is more likely with higher doses (10-25 mg QID or at bedtime) 4
Anticholinergic Effects
- Dry mouth (14% vs 5% with placebo) 3, 5
- Dry eyes 1
- Constipation 1
- Inhibition of micturition 1
- Increased risk for provocation of narrow-angle glaucoma 1
Cardiac Effects
- QT prolongation and Torsade de Pointes reported in post-marketing surveillance 3
- Abnormal ventricular repolarization when given in substantial doses or to susceptible individuals 6
- Risk is augmented when combined with phenothiazines (e.g., thioridazine), tricyclic antidepressants, antiparkinson drugs, atropine, quinidine, or procainamide 6
- These EKG abnormalities may increase the likelihood of dysrhythmias and sudden death 6
Dermatologic Reactions
- Acute Generalized Exanthematous Pustulosis (AGEP) 3
- Fixed drug eruptions 3
- Pruritus, rash, urticaria 3
Other Common Side Effects
- Weight gain (12% vs 10% with placebo) 5
- Loss of concentration (9% vs 8% with placebo) 5
- Insomnia (9% vs 6% with placebo) 5
- Irritability 7
- Allergic reactions 3
Special Population Risks
Elderly Patients
- Older adults are more sensitive to psychomotor impairment from hydroxyzine 1, 2, 4
- Increased risk for falls, fractures, and anticholinergic complications 1, 2
- Should start with lower doses and be monitored closely 2, 4
Pregnancy and Renal Impairment
- Hydroxyzine is contraindicated during early pregnancy 2, 4
- Dose should be halved in moderate renal impairment and avoided in severe renal impairment 2, 4
- Should be avoided in severe liver disease due to inappropriate sedating effects 2
Neonatal Withdrawal
- Neonatal withdrawal symptoms can occur with maternal use, including tremors, irritability, hyperactivity, jitteriness, shrill cry, myoclonic jerks, hypotonia, increased respiratory and heart rates, feeding problems, and clonic movements 1
- Withdrawal symptoms may last up to 5 weeks with treatment 1
Clinical Tolerance Patterns
- Sleepiness appears during the first week and may progressively diminish during continued treatment 5
- However, objective performance impairment does not demonstrate tolerance development over 5 days of administration 7
- Subjective symptoms are unreliable predictors of objective performance impairment 7