From the Guidelines
Hydroxyzine is associated with significant risks and side effects, including sedation, performance impairment, and anticholinergic effects, and its use should be approached with caution, especially in older adults and patients with comorbid conditions. The medication can cause drowsiness, dry mouth, headache, and constipation, and its sedative effect can impair driving and operating machinery, as noted in a study published in the Journal of Allergy and Clinical Immunology 1. Additionally, hydroxyzine can cause QT interval prolongation, potentially leading to serious heart rhythm problems, especially when combined with other QT-prolonging medications.
Some of the key risks and side effects associated with hydroxyzine include:
- Sedation and performance impairment, which can be particularly problematic in older adults and patients with comorbid conditions, such as those with increased intracranial pressure, benign prostatic hypertrophy, or preexisting cognitive impairment 1
- Anticholinergic effects, including dryness of mouth and eyes, constipation, inhibition of micturition, and an increased risk for provocation of narrow angle glaucoma 1
- Impaired learning and school performance in children, as well as driving impairment in adults, as reported in a large epidemiologic study 1
- Paradoxical CNS stimulation, which may occur particularly in children 1
- Increased risk of falls, fractures, and subdural hematomas in older adults, due to the medication's sedative and anticholinergic effects 1
A more recent study published in the Mayo Clinic Proceedings in 2021 highlights the importance of deprescribing medications like hydroxyzine in older adults, due to their potential for CNS impairment, delirium, and other adverse effects 1. Given the potential risks and side effects associated with hydroxyzine, it is essential to carefully weigh the benefits and risks of using this medication, especially in vulnerable populations, and to consider alternative treatments with a lower likelihood of adverse effects. Patients should always inform healthcare providers about all medications they're taking to avoid potentially dangerous drug interactions.
From the FDA Drug Label
THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS SUCH AS NARCOTICS, NON-NARCOTIC ANALGESICS AND BARBITURATES. QT Prolongation/Torsade de Pointes (TdP): Cases of QT prolongation and Torsade de Pointes have been reported during post-marketing use of hydroxyzine. Since drowsiness may occur with use of this drug, patients should be warned of this possibility and cautioned against driving a car or operating dangerous machinery while taking hydroxyzine. Acute Generalized Exanthematous Pustulosis (AGEP) Hydroxyzine may rarely cause acute generalized exanthematous pustulosis (AGEP), a serious skin reaction characterized by fever and numerous small, superficial, non-follicular, sterile pustules, arising within large areas of edematous erythema Skin and Appendages: Oral hydroxyzine hydrochloride is associated with Acute Generalized Exanthematous Pustulosis (AGEP) and fixed drug eruptions in post marketing reports. Side effects reported with the administration of hydroxyzine hydrochloride are usually mild and transitory in nature. Anticholinergic: Dry mouth Central Nervous System: Drowsiness is usually transitory and may disappear in a few days of continued therapy or upon reduction of dose. Involuntary motor activity including rare instances of tremor and convulsions have been reported, usually with doses considerably higher than those recommended. In post-marketing experience, the following additional undesirable effects have been reported: Cardiac System: QT prolongation, Torsade de Pointes. Body as a Whole: Allergic reaction. Nervous System: Headache. Psychiatric: Hallucination. Skin and Appendages: Pruritus, rash, urticaria.
The risks and side effects associated with hydroxyzine include:
- Cardiac risks: QT prolongation and Torsade de Pointes, particularly in patients with pre-existing heart disease or other risk factors for QT prolongation 2
- Central nervous system effects: drowsiness, involuntary motor activity, tremor, convulsions, and headache 2 2
- Anticholinergic effects: dry mouth 2
- Skin reactions: Acute Generalized Exanthematous Pustulosis (AGEP), fixed drug eruptions, pruritus, rash, and urticaria 2 2
- Psychiatric effects: hallucination 2
- Allergic reactions: allergic reaction 2 It is recommended to use hydroxyzine with caution in patients with risk factors for QT prolongation, and to advise patients against driving or operating machinery while taking the drug due to the risk of drowsiness 2.
From the Research
Risks and Side Effects of Hydroxyzine
The use of hydroxyzine, a first-generation antihistamine, is associated with several risks and side effects. These include:
- Sedation, impairment with decreased cognitive function, poor sleep quality, dry mouth, dizziness, and orthostatic hypotension 3
- Increased risk of accidents, intentional or unintentional overdoses, and sudden cardiac death 3
- Antimuscarinic effects, although less common than with other antihistamines like diphenhydramine 4
- Sleepiness/drowsiness, with a higher rate compared to other anxiolytic agents like benzodiazepines and buspirone 5
- Central nervous system depression, with mild cases being more likely in hydroxyzine-poisoned patients 4
- Respiratory depression, seizures, ventricular dysrhythmias, and intubation, although less likely in hydroxyzine-poisoned patients 4
Comparison with Other Antihistamines
Hydroxyzine has been compared to other antihistamines in terms of its efficacy and side effects. For example:
- Second-generation antihistamines like terfenadine, astemizole, loratadine, and cetirizine hydrochloride are just as effective as hydroxyzine but do not cause the same level of CNS and anticholinergic side effects 6
- Bedtime dosing of hydroxyzine can mitigate some of its side effects, such as reaction time degradation and adverse subjective symptoms 7
Special Considerations
It is worth noting that the risks and side effects associated with hydroxyzine can be influenced by various factors, including: