For my skilled‑nursing patient with anxiety, are any of her current medications (central nervous system depressants, anticholinergics, QT‑prolonging agents, monoamine‑oxidase inhibitors, or drugs requiring dose adjustment for renal/hepatic impairment) contraindications to adding hydroxyzine?

Critical Drug Interactions and Contraindications for Hydroxyzine in Skilled Nursing

Before ordering hydroxyzine for your skilled nursing patient, you must immediately screen for central nervous system depressants, QT-prolonging medications, and anticholinergic agents—any of which can cause life-threatening complications when combined with hydroxyzine.

Absolute Priority: CNS Depressants

Hydroxyzine potentiates all CNS depressants, requiring mandatory dose reduction of any concomitant sedating medication. 1 Specifically review her medication list for:

• Opioids (narcotics): The FDA explicitly warns that hydroxyzine enhances opioid effects, necessitating opioid dose reduction when used together 1
• Benzodiazepines: Concomitant use dramatically enhances sedation and performance impairment 2
• Barbiturates: Require dose reduction when combined with hydroxyzine 1
• Non-narcotic analgesics with sedating properties: Must be used cautiously 1

The risk is particularly severe in elderly skilled nursing patients, who experience confusion, over-sedation, and falls with sedating drugs. 1 Hydroxyzine causes 80% sedation rates and significantly prolongs reaction times even at standard doses. 3

High-Risk: QT-Prolonging Agents

Hydroxyzine prolongs the QT interval and has caused torsade de pointes in post-marketing surveillance. 1 The majority of these cases occurred in patients taking other QT-prolonging drugs. 1, 4 You must identify if she is taking:

• Class IA antiarrhythmics: quinidine, procainamide 1
• Class III antiarrhythmics: amiodarone, sotalol 1
• Antipsychotics: ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine 1
• Antidepressants: citalopram, fluoxetine 1
• Antibiotics: azithromycin, erythromycin, clarithromycin, gatifloxacin, moxifloxacin 1
• Other agents: pentamidine, methadone, ondansetron, droperidol 1

If she has any of these medications plus underlying cardiovascular disease (recent MI, uncompensated heart failure, bradyarrhythmias, congenital long QT syndrome), hydroxyzine is contraindicated. 1 The combination of cardiovascular disorders plus arrhythmogenic drugs represents the greatest combined risk factor for QT prolongation and torsade de pointes. 4

Significant Concern: Anticholinergic Medications

Hydroxyzine has potent anticholinergic effects that are additive with other anticholinergic agents. 3 In elderly patients, this combination causes:

• CNS impairment and delirium 3
• Impaired vision 3
• Urinary retention 3
• Constipation 3
• Increased fall risk 3

Hydroxyzine is specifically listed among anticholinergic medications that should be avoided or deprescribed in older adults. 3 Check for:

• Old antihistamines: diphenhydramine 3
• Muscle relaxants: cyclobenzaprine, metaxalone 3
• Overactive bladder medications: oxybutynin 3
• Tricyclic antidepressants 3

Mandatory Screening for Underlying Conditions

Beyond drug interactions, verify she does not have:

• Severe hepatic disease: Hydroxyzine is absolutely contraindicated due to risk of excessive sedation and hepatic encephalopathy 2
• Severe renal impairment (CrCl <10 mL/min): Hydroxyzine must be avoided entirely 5
• Moderate renal impairment (CrCl 10-20 mL/min): Requires 50% dose reduction 5, 2
• Prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment: Anticholinergic effects are particularly dangerous 2
• Pre-existing heart disease, electrolyte imbalances, or recent myocardial infarction: Increases QT prolongation risk 1

Critical Clinical Algorithm

1. Review her complete medication list for any CNS depressants, QT-prolonging agents, or anticholinergics listed above
2. If she is taking opioids, benzodiazepines, or barbiturates: Plan to reduce those doses by approximately 50% when adding hydroxyzine 1
3. If she is taking any QT-prolonging medication: Obtain baseline ECG and assess for additional cardiac risk factors before prescribing hydroxyzine 1
4. If she has multiple anticholinergic medications: Consider alternative anxiolytic agents (e.g., SSRIs) rather than adding hydroxyzine 3
5. Check renal function: If CrCl 10-20 mL/min, start hydroxyzine at 50% of standard dose; if CrCl <10 mL/min, do not prescribe 5, 2
6. Assess hepatic function: If severe liver disease is present, hydroxyzine is contraindicated 2

Common Pitfall to Avoid

Do not assume hydroxyzine is "just an antihistamine" and therefore safe. 6 Recent data show hydroxyzine became the most identified antihistamine in impaired driving investigations in 2023, outpacing diphenhydramine, with drivers exhibiting incoordination, slurred speech, and erratic driving. 6 In skilled nursing patients taking multiple medications, the risk of severe CNS depression, falls, and cardiac arrhythmias is substantially amplified. 1, 4