Is hydroxyzine safe to use in patients taking Eliquis (apixaban)?

Hydroxyzine Safety with Apixaban (Eliquis)

Yes, hydroxyzine can be used with apixaban, but requires careful risk assessment for cardiac arrhythmias and bleeding risk—the combination itself has no direct pharmacokinetic interaction, but hydroxyzine carries independent cardiac risks that warrant monitoring.

Key Safety Considerations

No Direct Drug-Drug Interaction

• Apixaban is metabolized primarily via CYP3A4 and is a substrate of P-glycoprotein 1, 2
• Hydroxyzine does not significantly inhibit or induce CYP3A4 or P-glycoprotein pathways, so no direct pharmacokinetic interaction exists between these medications
• The American College of Cardiology emphasizes monitoring apixaban's CYP3A4 metabolism when prescribing with other medications, but hydroxyzine is not listed as a problematic interacting agent 1

Independent Cardiac Risk from Hydroxyzine

• Hydroxyzine carries conditional risk for QT prolongation and torsade de pointes (TdP), particularly in patients with underlying cardiac risk factors 3
• A comprehensive pharmacovigilance review identified 59 reports of QT prolongation and/or TdP potentially linked to hydroxyzine use between 1955 and 2016 3
• All cases (excluding intentional overdose) involved underlying medical conditions or concomitant medications constituting additional risk factors 3
• The combination of cardiovascular disorders plus concomitant arrhythmogenic drugs was identified as the greatest combined risk factor 3
• Hydroxyzine demonstrates concentration-dependent inhibition of human cardiac ion channels, including hERG potassium channels 3

Clinical Case Evidence

• One documented case of hydroxyzine-induced supraventricular tachycardia occurred in a 9-year-old with no underlying cardiac abnormalities, which resolved after discontinuing hydroxyzine 4
• Interestingly, hydroxyzine was successfully used to treat a cutaneous adverse reaction to apixaban itself, demonstrating practical concurrent use in clinical practice 5

Risk Stratification Algorithm

Proceed with Standard Dosing if:

• No underlying cardiac disease (structural heart disease, heart failure, cardiomyopathy)
• No QT-prolonging medications (antiarrhythmics, certain antibiotics, antipsychotics)
• No electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia)
• Normal renal function (CrCl >30 mL/min) 1
• No hepatic impairment 1

Use with Enhanced Monitoring if:

• Age >75 years (increased bleeding risk with apixaban and potential cardiac sensitivity) 2
• Moderate renal impairment (CrCl 30-50 mL/min), as this affects apixaban clearance 1, 2
• Known atrial fibrillation (the likely indication for apixaban, but also a cardiac risk factor)
• History of palpitations or arrhythmias

Avoid or Choose Alternative if:

• Severe renal impairment (CrCl <30 mL/min) 1
• Known long QT syndrome or family history of sudden cardiac death
• Multiple concurrent QT-prolonging medications
• Recent cardiac events or unstable cardiac status
• Uncorrected electrolyte abnormalities

Practical Management Recommendations

Baseline Assessment

• Obtain baseline ECG if any cardiac risk factors are present 3
• Check electrolytes (potassium, magnesium, calcium) before initiating hydroxyzine 3
• Verify renal function to ensure appropriate apixaban dosing 1, 2

Monitoring Strategy

• The National Comprehensive Cancer Network recommends monitoring for bleeding signs with apixaban (unusual bruising, nosebleeds, bleeding gums) 6
• Monitor for cardiac symptoms (palpitations, chest tightness, syncope) that could indicate arrhythmia 4
• Regular renal function monitoring is advisable as changes affect apixaban clearance 1

Common Pitfalls to Avoid

• Do not assume hydroxyzine is completely benign simply because it's an antihistamine—it has documented cardiac risks 3
• Do not overlook the cumulative effect of multiple medications that individually have low arrhythmia risk 3
• The American Heart Association advises against abruptly stopping apixaban, as this increases stroke risk in atrial fibrillation patients 6

Alternative Considerations

• If cardiac risk factors are significant, consider second-generation antihistamines (cetirizine, loratadine) which lack the cardiac effects of hydroxyzine
• Hydroxyzine demonstrated efficacy and safety in generalized anxiety disorder trials with drowsiness as the main side effect, comparable to benzodiazepines 7