What are the common and serious side effects of hydroxyzine, and what precautions should be taken?

Hydroxyzine Side Effects

Hydroxyzine commonly causes sedation and dry mouth, with serious but rare risks including QT prolongation, cardiac arrhythmias (Torsade de Pointes), and acute generalized exanthematous pustulosis (AGEP), requiring careful patient selection and monitoring, particularly in elderly patients and those with cardiac risk factors. 1

Common Side Effects

Sedative Effects

• Short-term sedation and drowsiness are the most frequently reported adverse effects, occurring commonly enough to warrant warnings against driving or operating machinery 2, 1
• Performance impairment can occur without subjective awareness of drowsiness, with drivers in fatal accidents being 1.5 times more likely to be taking first-generation antihistamines like hydroxyzine 3
• Sedation is dose-dependent; lower doses (0.7 mg/kg) cause significantly less sedation than higher doses (1.4 mg/kg) while maintaining therapeutic efficacy 4

Anticholinergic Effects

• Dry mouth (xerostomia) is a common anticholinergic side effect 5, 6
• Weakness has been reported in clinical trials 2
• Elderly patients are particularly vulnerable to anticholinergic effects including confusion and over-sedation 3, 1

Sleep-Related Effects

• Hydroxyzine can alter sleep architecture and trigger nightmares, particularly with bedtime dosing, by affecting serotonin, norepinephrine, dopamine, GABA, and acetylcholine neurotransmitters 7
• Higher doses (10-25 mg QID or at bedtime) may increase the risk of disturbed dreaming 7

Serious Side Effects

Cardiac Toxicity

• QT prolongation and Torsade de Pointes have been reported during post-marketing surveillance, with the majority occurring in patients with pre-existing risk factors 1
• Hydroxyzine should be used with extreme caution in patients with congenital long QT syndrome, family history of long QT syndrome, recent myocardial infarction, uncompensated heart failure, bradyarrhythmias, or electrolyte imbalances 1
• Abnormal ventricular repolarization can occur with substantial doses or in susceptible individuals, potentially increasing the likelihood of dysrhythmias and sudden death 8

Dangerous Drug Interactions

• Hydroxyzine potentiates central nervous system depressants (narcotics, non-narcotic analgesics, barbiturates), requiring dose reduction of concomitant CNS depressants 1
• Caution is mandatory with drugs that prolong QT interval, including Class 1A antiarrhythmics (quinidine, procainamide), Class III antiarrhythmics (amiodarone, sotalol), certain antipsychotics (ziprasidone, clozapine, quetiapine), antidepressants (citalopram, fluoxetine), and antibiotics (azithromycin, erythromycin, moxifloxacin) 1
• Phenothiazines, tricyclic antidepressants, antiparkinson drugs, atropine, quinidine, or procainamide may augment cardiac effects 8

Severe Skin Reactions

• Acute Generalized Exanthematous Pustulosis (AGEP) is a rare but serious skin reaction characterized by fever and numerous small, superficial, sterile pustules arising within large areas of edematous erythema 1
• Hydroxyzine must be discontinued immediately at the first appearance of skin rash or worsening of pre-existing skin reactions 1
• Cross-sensitivity exists with cetirizine and levocetirizine; these agents should be avoided in patients who have experienced AGEP with hydroxyzine 1

Respiratory Complications

• Respiratory complications can occur due to synergistic reactions when hydroxyzine is combined with other sedatives 5

Special Population Considerations

Elderly Patients

• Start with the lowest dose and observe closely, as elderly patients are more sensitive to psychomotor impairment and at increased risk for falls, fractures, and anticholinergic effects 3, 1
• Sedating drugs may cause confusion and over-sedation in the elderly 1
• Dose selection should be cautious due to greater frequency of decreased hepatic, renal, or cardiac function 1

Renal Impairment

• Dose should be halved in moderate renal impairment and avoided in severe renal impairment 7, 3
• The extent of renal excretion has not been fully determined, requiring careful dose selection 1

Pregnancy

• Hydroxyzine is contraindicated during early pregnancy 7, 3

Pediatric Patients

• In children with atopic dermatitis, sedation was the only adverse effect reported at therapeutic doses 4
• Hydroxyzine is considered safe in pediatric dental sedation when proper dosage is used, with drowsiness and dry mouth being the primary adverse events 5

Risk Mitigation Strategies

For Nightmares

• Adjust timing of administration by taking hydroxyzine earlier in the evening rather than at bedtime 7
• Consider dose reduction while maintaining therapeutic benefit 7
• Switch to second-generation antihistamines with less CNS penetration for daytime use 7

For Sedation and Performance Impairment

• Warn patients explicitly about impaired driving ability and work performance 3, 1
• Advise against simultaneous use of alcohol and other CNS depressants 1
• Consider using hydroxyzine only at bedtime in combination with non-sedating antihistamines during the day 3

For Cardiac Risk

• Screen for QT prolongation risk factors before initiating therapy 1
• Review all concomitant medications for QT-prolonging potential 1
• Consider baseline ECG in high-risk patients 8