What is the potential drug interaction between hydroxyzine and Eliquis (apixaban)?

Drug Interaction Between Hydroxyzine and Apixaban (Eliquis)

There is no significant clinically relevant drug interaction between hydroxyzine and apixaban (Eliquis) that would require dose adjustment or contraindicate their concurrent use.

Mechanism of Potential Interaction

Hydroxyzine and apixaban have different metabolic pathways and elimination routes that minimize the risk of significant interaction:

• Apixaban metabolism:

  • Primarily metabolized by CYP3A4/5
  • Also a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters
  • Interactions occur mainly with strong CYP3A4 and P-gp inhibitors or inducers

• Hydroxyzine metabolism:

  • Metabolized primarily by CYP2D6
  • Not known to be a significant inhibitor or inducer of CYP3A4 or P-gp

Evidence Assessment

The European Heart Rhythm Association practical guide on NOACs (2018) does not list hydroxyzine among medications that interact with apixaban or other NOACs 1. This authoritative guideline provides comprehensive tables of drug interactions with NOACs, and the absence of hydroxyzine from these tables suggests no significant interaction.

Similarly, the practical recommendations for combining medications with direct oral anticoagulants do not mention hydroxyzine as a medication of concern 1. The guidelines focus on medications that are strong inhibitors or inducers of CYP3A4 and P-gp pathways, which hydroxyzine is not.

Clinical Implications

When prescribing hydroxyzine with apixaban:

• No dose adjustment of either medication is required
• No additional monitoring beyond standard practice is necessary
• The combination can be safely used in patients requiring both medications

Important Considerations

While the specific combination appears safe, clinicians should be aware of:

1. Sedative effects: Hydroxyzine has sedative properties that may compound with other CNS depressants

2. Patient-specific factors: Renal impairment, advanced age, or low body weight may increase sensitivity to either medication independently

3. Polypharmacy: The risk of interactions increases with the number of medications a patient takes. If the patient is on multiple medications, particularly those that affect CYP3A4 or P-gp (like amiodarone, verapamil, or dronedarone), closer monitoring may be warranted 1, 2

Contrast with Known Interacting Medications

Unlike hydroxyzine, the following medications do have significant interactions with apixaban:

• Strong CYP3A4/P-gp inhibitors: Ketoconazole, itraconazole, ritonavir (require dose reduction)
• Strong CYP3A4/P-gp inducers: Rifampin, phenytoin, carbamazepine, St. John's wort (may reduce apixaban efficacy)
• Other anticoagulants, antiplatelets, NSAIDs: Increase bleeding risk through pharmacodynamic interactions 3, 4

Conclusion

Based on the available evidence, hydroxyzine and apixaban can be safely co-administered without specific dose adjustments or additional monitoring beyond standard practice. This combination does not appear in any contraindication lists in current clinical guidelines for NOAC management.