When can Eliquis (apixaban) be started after stopping fluoxetine?

When to Start Eliquis After Stopping Fluoxetine

Eliquis (apixaban) can be started immediately after stopping fluoxetine, as there is no required washout period between these medications.

Rationale for Immediate Initiation

The provided evidence does not identify any pharmacokinetic or pharmacodynamic interaction requiring a waiting period between discontinuing fluoxetine and initiating apixaban. These medications work through entirely different mechanisms:

• Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that affects platelet function and may modestly increase bleeding risk through serotonin depletion in platelets 1
• Apixaban is a direct factor Xa inhibitor with predictable pharmacological properties that does not require routine monitoring 2

Key Clinical Considerations

Bleeding Risk Assessment

While no drug-drug interaction necessitates a washout period, you should assess the patient's overall bleeding risk before initiating apixaban:

• Age >75 years is an independent bleeding risk factor 1
• Previous bleeding history significantly increases major bleeding risk 1
• Renal function must be evaluated, as 27% of apixaban is renally excreted 1
• Concomitant antiplatelet therapy substantially increases bleeding risk 1

Fluoxetine's Residual Effects

Although fluoxetine can be stopped immediately before starting apixaban, be aware that:

• Fluoxetine has a long half-life (4-6 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine), meaning antiplatelet effects may persist for weeks after discontinuation 1
• This residual effect does not contraindicate apixaban initiation but should be factored into your overall bleeding risk assessment 1

Apixaban Dosing Considerations

Standard dose: 5 mg twice daily for most indications 1

Reduced dose (2.5 mg twice daily) is indicated when ≥2 of the following criteria are met 1, 3:

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL (133 μmol/L)

Special Populations Requiring Attention

• Chronic kidney disease: Apixaban levels may be prolonged; in one case, detectable anti-Xa levels persisted >10 days after the last dose in a patient with renal insufficiency 4
• Elderly patients (>75 years): Limited data exist, but standard dosing principles apply unless dose-reduction criteria are met 5
• Cancer patients: Apixaban is safe and effective, though this population has not been extensively studied 5

Practical Algorithm

1. Stop fluoxetine (no washout required)
2. Assess bleeding risk factors including age, prior bleeding, renal function, and concomitant medications 1
3. Check renal function to determine appropriate apixaban dosing 1
4. Apply dose-reduction criteria if ≥2 factors present 1, 3
5. Initiate apixaban immediately at the appropriate dose
6. Consider gastric protection with proton pump inhibitors if multiple bleeding risk factors are present 1

Common Pitfalls to Avoid

• Do not delay apixaban initiation waiting for fluoxetine "washout"—this unnecessarily prolongs the period without anticoagulation and increases thromboembolic risk
• Do not assume all patients need dose reduction; inappropriately reduced dosing occurred in 57% of reduced-dose patients in one study 3
• Do not forget to assess renal function, as this is critical for both safety and appropriate dosing 4, 5