What is the best course of action for a 71-year-old male patient experiencing confusion, taking hydroxyzine (hydroxyzine) 100 mg every 6-8 hours, exceeding the prescribed dose of 50 mg every six hours, with a history of a rash on his right lower leg?

Immediate Management of Hydroxyzine Overdose with Confusion

Immediately discontinue hydroxyzine and evaluate for anticholinergic toxicity—this 71-year-old patient is taking double the prescribed dose (100 mg every 6-8 hours instead of 50 mg every 6 hours), placing him at high risk for hypersedation, cognitive impairment, and potentially life-threatening complications in an elderly individual. 1, 2

Immediate Actions Required

Stop Hydroxyzine Immediately

• The patient's confusion is most likely hydroxyzine-induced hypersedation and anticholinergic toxicity, given he is taking 400-600 mg daily (far exceeding recommended doses of 10-50 mg at bedtime for elderly patients) 3
• The FDA label explicitly identifies hypersedation as the most common manifestation of hydroxyzine overdosage, with other signs including confusion, stupor, nausea, and convulsions 2
• Older adults are particularly vulnerable to psychomotor impairment, falls, fractures, subdural hematomas, and cognitive impairment from first-generation antihistamines like hydroxyzine 1

Monitor for Serious Complications

• Obtain an ECG immediately—hydroxyzine overdose can cause QT prolongation and Torsade de Pointes, which can be fatal 2, 4
• Monitor vital signs frequently and observe closely for deterioration 2
• Assess for anticholinergic signs: dry mouth, urinary retention, constipation, dilated pupils, and worsening confusion 1
• Check for concurrent medications that may potentiate cardiac risks (antidepressants, antipsychotics, other QT-prolonging drugs) 4

Supportive Care

• There is no specific antidote for hydroxyzine overdose 2
• If the patient is alert enough, consider activated charcoal if presentation is within 1-2 hours of last dose (though given 4+ days of overdosing, this may have limited utility) 2
• Maintain IV access and provide supportive care with IV fluids if needed 2
• Do NOT use epinephrine if hypotension develops—hydroxyzine counteracts its pressor action; use levarterenol or metaraminol instead 2

Addressing the Underlying Rash

Reassess the Diagnosis

• The rash on the right lower leg needs urgent re-evaluation—hydroxyzine was an inappropriate first-line choice for a leg rash in an elderly patient 1
• Consider cellulitis, contact dermatitis, or other dermatological conditions that require specific treatment, not just symptomatic antihistamine therapy 1
• Paradoxically, hydroxyzine can worsen certain dermatological conditions in sensitized patients, particularly those with ethylenediamine sensitivity 5, 6

Alternative Management

• If antihistamine therapy is truly needed for pruritus after the acute confusion resolves, switch to a second-generation non-sedating antihistamine (cetirizine, loratadine, fexofenadine) which have significantly lower risk of cognitive impairment and sedation 1
• The British Journal of Dermatology explicitly states that second-generation antihistamines are generally preferred over first-generation antihistamines for safety reasons 1

Disposition and Follow-Up

Hospital Admission Considerations

• Strong consideration for admission given:
  • Age 71 with acute confusion (delirium)
  • Significant overdose (2-4x prescribed dose over multiple days)
  • Need for cardiac monitoring (QT prolongation risk) 2, 4
  • Fall risk and need for close observation 1

If Discharged After Stabilization

• Ensure family understands hydroxyzine is discontinued permanently
• Remove all hydroxyzine from the home to prevent accidental re-exposure
• Provide clear written instructions about the dangers of first-generation antihistamines in elderly patients 1
• Arrange close follow-up within 24-48 hours to reassess mental status and the leg rash
• Consider cognitive assessment once acute toxicity resolves to establish baseline

Critical Pitfalls to Avoid

• Never restart hydroxyzine in this patient—elderly patients have heightened sensitivity to anticholinergic effects and sedation 1, 3
• Do not attribute confusion to "normal aging" or other causes without first addressing the obvious medication overdose 1
• Do not discharge without ensuring the family understands proper medication administration and the specific risks of this overdose 1
• Remember that cognitive impairment can persist beyond plasma drug levels due to prolonged end-organ effects 1