Hydroxyzine and Glutathione: Side Effects Profile
Hydroxyzine carries significant sedative, anticholinergic, and performance-impairing side effects that can occur even without subjective awareness of drowsiness, while glutathione as an antioxidant supplement has minimal documented adverse effects and no known clinically significant drug interactions with hydroxyzine.
Hydroxyzine Side Effects
Central Nervous System Effects
- Sedation and performance impairment are the most clinically significant concerns, with drivers taking first-generation antihistamines like hydroxyzine being 1.5 times more likely to be responsible for fatal automobile accidents 1
- Performance impairment can exist without subjective awareness of drowsiness, meaning patients may feel alert while actually experiencing cognitive deficits 1, 2
- Impaired driving performance with hydroxyzine worsens with concurrent activities like cell phone use 1, 2
- Workers taking hydroxyzine exhibit impaired work performance, reduced productivity, and increased risk of occupational accidents 1
- In children, hydroxyzine has been associated with impaired learning and school performance 1
- Paradoxical CNS stimulation may occur, particularly in children 1
Anticholinergic Effects
- Dry mouth and dry eyes 1
- Constipation 1
- Urinary retention/inhibition of micturition 1
- Increased risk for provoking narrow-angle glaucoma 1
Cardiovascular Concerns
- Elevated heart rate and blood pressure 3
- Abnormal ventricular repolarization when given in substantial doses or to susceptible individuals, with potential for dysrhythmias and sudden death when combined with phenothiazines, tricyclic antidepressants, quinidine, or procainamide 3
Other Notable Side Effects
- Ototoxicity: Hydroxyzine showed an adjusted hazard ratio of 2.20 (1.05-4.60) for bilateral hearing loss in a large cohort study, suggesting clinicians should avoid co-administration with other confirmed ototoxic drugs 4
- Sleepiness/drowsiness occurs at higher rates compared to other anxiolytic agents 5
- In overdose, hydroxyzine produces less antimuscarinic toxicity than diphenhydramine, with more mild CNS depression being the predominant feature 6
Special Population Considerations
Elderly Patients
- More sensitive to psychomotor impairment from hydroxyzine 1, 2
- Increased risk for falls, fractures, and subdural hematomas 1
- More susceptible to adverse anticholinergic effects 1
- Should start with lower doses and be monitored closely 2
Renal Impairment
- Dose should be halved in moderate renal impairment 1, 2
- Should be avoided in severe renal impairment (creatinine clearance <10 mL/min) 1, 2
Hepatic Impairment
- Should be avoided in severe liver disease because sedating effects are inappropriate 1
Pregnancy
- Contraindicated during early pregnancy 1, 2
- Best to avoid throughout pregnancy, especially during the first trimester 1
Drug Interactions to Avoid
- Concomitant use with other CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) further enhances performance impairment 1
- Combination with opioids increases sedation risk 1
- Cardiac medications (phenothiazines, tricyclic antidepressants, quinidine, procainamide) may augment cardiac effects 3
Glutathione Safety Profile
Glutathione as an antioxidant supplement has minimal documented adverse effects in the medical literature. There are no known clinically significant drug interactions between glutathione and hydroxyzine based on available evidence.
Clinical Pitfalls
- Do not assume patients are unimpaired simply because they deny sedation—objective performance deficits can exist without subjective drowsiness 1, 2
- Avoid AM/PM dosing strategies (second-generation antihistamine in morning, hydroxyzine at night) as hydroxyzine's prolonged half-life causes next-morning impairment 1, 2
- Even bedtime-only dosing of hydroxyzine can cause significant daytime drowsiness and decreased alertness 1
- Second-generation antihistamines are generally preferred over hydroxyzine for daytime use due to reduced sedative effects 1, 2