Can hydroxyzine (antihistamine) cause hypotension?

Can Hydroxyzine Cause Hypotension?

Yes, hydroxyzine can cause hypotension, particularly in the setting of overdose, when combined with other CNS depressants, or in vulnerable populations such as elderly patients and those with cardiovascular instability.

Mechanism and Clinical Context

Hydroxyzine's hypotensive effects stem from multiple mechanisms:

• Histamine release: As a first-generation antihistamine, hydroxyzine can trigger histamine release, which may cause hypotension, particularly in unstable cardiac or trauma patients 1
• CNS depression: The sedating properties can contribute to orthostatic hypotension through reduced sympathetic tone 2
• Anticholinergic effects: These may impair compensatory cardiovascular responses 1, 2

Specific Clinical Scenarios Where Hypotension Occurs

Overdose Situations

The FDA label explicitly states that hypotension may occur in hydroxyzine overdose and should be controlled with intravenous fluids and levarterenol or metaraminol 3. Critically, epinephrine should NOT be used as hydroxyzine counteracts its pressor action 3.

Perioperative and Acute Care Settings

• During peribulbar blocks, hydroxyzine premedication (1.0 mg/kg) was associated with bradycardia and paradoxical hypertension rather than hypotension, though this represents a specific procedural context 4
• In patients with cardiovascular instability or trauma, histamine release from hydroxyzine may precipitate hypotension 1
• Morphine (used for infundibular spasm) carries explicit warnings about histamine-induced hypotension in unstable patients, and the same caution applies to hydroxyzine 1

Drug Interactions Increasing Hypotension Risk

Concomitant use with other CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) significantly enhances the risk of hypotension 2. This is particularly concerning because:

• Multiple CNS depressants have additive effects on cardiovascular depression 2
• Elderly patients are at increased risk for falls and syncope from orthostatic hypotension 2, 5
• The combination may require careful hemodynamic monitoring 5

High-Risk Populations

Elderly Patients

Older adults are more sensitive to psychomotor impairment and cardiovascular effects from hydroxyzine, with increased risk for falls, fractures, and complications 1, 2, 5. The British Journal of Dermatology specifically recommends starting elderly patients on low doses and monitoring closely for confusion, over-sedation, and fall risk 6.

Patients with Organ Dysfunction

• Severe renal impairment (creatinine clearance <10 mL/min): Hydroxyzine should be avoided entirely 1, 6
• Moderate renal impairment (creatinine clearance 10-20 mL/min): Dose should be halved 1, 6
• Severe liver disease: Hydroxyzine should be avoided due to inappropriate sedating effects that may precipitate coma 1, 6

Cardiovascular Disease

Patients with mast cell activation syndrome or those prone to cardiovascular events should avoid hydroxyzine due to concerns about hemodynamic instability 5. The drug may also cause abnormal ventricular repolarization, particularly when given in substantial doses or to susceptible individuals 7.

Clinical Monitoring Recommendations

When hydroxyzine must be used despite hypotension risk:

• Monitor vital signs frequently, particularly blood pressure in both supine and standing positions 3
• ECG monitoring is recommended in overdose cases due to risk of QT prolongation and Torsade de Pointes 3
• Avoid epinephrine for hypotension management as hydroxyzine counteracts its pressor action; use levarterenol or metaraminol instead 3
• Ensure adequate hydration and consider intravenous fluids if hypotension develops 3

Common Pitfalls to Avoid

• Do not assume bedtime-only dosing eliminates cardiovascular risk: Performance impairment and cardiovascular effects persist longer than plasma levels due to prolonged half-lives of hydroxyzine and its metabolites 2
• Do not combine with multiple CNS depressants without careful monitoring, as this substantially increases hypotension risk 2, 5
• Do not use in elderly patients without compelling indication, given their increased sensitivity to adverse cardiovascular effects 1, 2, 5
• Do not overlook renal and hepatic function before prescribing, as these significantly affect drug clearance and risk profile 1, 6