Itraconazole and Apixaban Interaction: Significant Risk Requiring Dose Adjustment
Concomitant use of itraconazole with apixaban requires a 50% dose reduction of apixaban due to the significant risk of bleeding from increased apixaban exposure, as itraconazole is a combined P-glycoprotein and strong CYP3A4 inhibitor. 1
Mechanism of Interaction
Itraconazole significantly affects apixaban pharmacokinetics through two primary mechanisms:
CYP3A4 Inhibition: Itraconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system, which is responsible for metabolizing apixaban 2
P-glycoprotein Inhibition: Itraconazole also inhibits P-glycoprotein, a transport protein that affects apixaban absorption and elimination 1
These combined effects result in increased systemic exposure to apixaban, significantly elevating bleeding risk.
Clinical Recommendations
Dosing Adjustments
For patients on apixaban 5 mg or 10 mg twice daily: Decrease apixaban dose by 50% when coadministered with itraconazole 1
For patients on apixaban 2.5 mg twice daily: Avoid coadministration with itraconazole completely, as further dose reduction is not possible 1
Monitoring Recommendations
If coadministration cannot be avoided:
- Monitor closely for signs of bleeding (bruising, epistaxis, hematuria, melena)
- Consider more frequent clinical follow-up during the period of coadministration
- Be vigilant for signs of QTc prolongation, as itraconazole may also affect cardiac conduction 2
Alternative Approaches
When possible, consider these alternatives:
Alternative antifungal therapy: If clinically appropriate, select an antifungal with less significant interaction potential
Temporary anticoagulation adjustment: If short-term antifungal therapy is needed, consider temporary adjustment of anticoagulation strategy under specialist guidance
Therapeutic drug monitoring: For patients requiring both medications, therapeutic drug monitoring of itraconazole may help optimize dosing 2, 3
Common Pitfalls and Caveats
Underestimation of interaction: The interaction between itraconazole and apixaban is significant and potentially dangerous, not merely theoretical 1
Multiple medications: Patients on multiple medications may have additional drug interactions that further compound bleeding risk 4, 5
OTC medications: Patients may not report over-the-counter medications or supplements that could further increase bleeding risk when combined with this interaction 5
Duration of effect: The inhibitory effects of itraconazole may persist for days after discontinuation due to its long half-life 6
Cardiac considerations: Itraconazole has negative inotropic properties and is contraindicated in patients with decreased cardiac ejection fraction or history of congestive heart failure 2
This significant drug interaction requires careful management to prevent potentially serious bleeding complications while ensuring effective treatment of both the underlying conditions requiring anticoagulation and fungal infection.