Is ELIQUIS (apixaban) suitable for this patient?

ELIQUIS (Apixaban) Suitability Assessment

FDA-Approved Indications

ELIQUIS is FDA-approved for three primary indications: reducing stroke/systemic embolism risk in nonvalvular atrial fibrillation, VTE prophylaxis after hip/knee replacement surgery, and treatment/prevention of DVT and PE 1.

Absolute Contraindications

Before prescribing ELIQUIS, verify the patient does NOT have:

• Active pathological bleeding - ELIQUIS must be discontinued immediately if present 1
• Prosthetic heart valves - safety and efficacy have not been established; use is not recommended 1
• Triple-positive antiphospholipid syndrome (positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies) - DOACs including apixaban are associated with increased recurrent thrombotic events compared to warfarin 1
• Severe renal impairment (CrCl <15 mL/min) - apixaban should be avoided 2
• Hemodynamically unstable PE or patients requiring thrombolysis/pulmonary embolectomy - unfractionated heparin is preferred for initial treatment 1

Renal Function Assessment

Check creatinine clearance before initiating ELIQUIS:

• CrCl ≥30 mL/min: Standard dosing appropriate 2
• CrCl 15-29 mL/min: Use with extreme caution; apixaban was not studied in patients with CrCl <25 mL/min 2
• CrCl <15 mL/min: Avoid use 2

Approximately 27% of apixaban undergoes renal elimination, making renal function critical for dosing decisions 2.

Hepatic Function Considerations

Evaluate liver function before prescribing:

• Mild hepatic impairment: No significant dose adjustment needed 2
• Moderate hepatic impairment (Child-Pugh B): Apixaban exposure not significantly increased; can be used 2
• Severe hepatic impairment: Clinical trial data excluded patients with transaminases >2× upper limit of normal or total bilirubin >1.5× upper limit of normal 2

Apixaban is primarily metabolized via CYP3A4-dependent pathways in the liver 2.

Drug Interaction Screening

Identify and manage critical drug interactions:

Strong CYP3A4 and P-gp Inhibitors

• Combined strong inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): Reduce apixaban dose by 50% if on 5-10 mg twice daily; avoid combination if on 2.5 mg twice daily 2
• Clarithromycin specifically has been associated with higher major bleeding rates in retrospective studies 2

Strong CYP3A4 and P-gp Inducers

• Combined strong inducers (e.g., rifampin, carbamazepine, phenytoin): Avoid combination - significantly decreases apixaban exposure and increases thrombotic risk 2

NSAIDs Including Topical Diclofenac (Voltaren Gel)

• NSAIDs increase bleeding risk when combined with anticoagulants and can cause cardiovascular thrombotic events 3
• Acetaminophen is the preferred first-line analgesic due to lack of antiplatelet effects 3
• If NSAIDs are unavoidable, use the shortest duration possible with close monitoring for bleeding 3

Cancer-Specific Considerations

For patients with active malignancy, apixaban has specific evidence:

• Pancreatic cancer (locally advanced/metastatic): Apixaban is recommended for primary VTE prophylaxis in ambulatory patients on systemic therapy with low bleeding risk 2
• Intermediate-to-high VTE risk (Khorana score ≥2): Apixaban is recommended for ambulatory patients receiving systemic anticancer therapy who are not actively bleeding 2
• Multiple myeloma on immunomodulatory drugs: Apixaban at prophylactic doses can be used as an alternative to LMWH or aspirin 2
• Cancer-associated VTE treatment: Apixaban demonstrated noninferiority to dalteparin for treating cancer-associated VTE without increased major bleeding (5.6% recurrence vs 7.9% with dalteparin; 3.8% major bleeding vs 4.0%) 4

Perioperative Management

If surgery or invasive procedure is planned:

Preoperative Discontinuation

• Low bleeding risk procedures: Stop apixaban 24 hours (1 day) before procedure - corresponds to approximately 2-3 half-lives 2
• High bleeding risk procedures (e.g., major abdominal surgery): Stop apixaban 48 hours (2 days) before procedure - corresponds to approximately 4 half-lives 2

Postoperative Resumption

• Low bleeding risk surgery: Resume full dose (5 mg twice daily) 24 hours after surgery 2
• High bleeding risk surgery: Resume reduced dose (2.5 mg twice daily) 48-72 hours after surgery, then increase to full dose 2

Neuraxial Anesthesia Precautions

• Do not remove epidural/intrathecal catheters earlier than 24 hours after last apixaban dose 1
• Do not administer next apixaban dose earlier than 5 hours after catheter removal 1
• If traumatic puncture occurs, delay apixaban for 48 hours 1

Bleeding Risk Assessment

Monitor for signs of bleeding and counsel patients on:

• Major bleeding rates in clinical trials: 2.13% per year with apixaban vs 3.09% with warfarin in atrial fibrillation 1
• Intracranial hemorrhage: 0.33% per year with apixaban vs 0.82% with warfarin 1
• Reversal agent available: Andexanet alfa can reverse anti-factor Xa activity 1
• Pharmacodynamic effect persists at least 24 hours after last dose (approximately two half-lives) 1

Special Population Considerations

Elderly Patients (>75 years)

• Require closer monitoring for bleeding complications due to age-related physiological changes 5
• No routine dose adjustment based solely on age unless combined with other risk factors 5

Hospitalized Medically Ill Patients

• DOACs including apixaban are NOT routinely recommended for VTE prophylaxis in hospitalized medical patients 2
• LMWH, fondaparinux, or unfractionated heparin are preferred 2

Monitoring Requirements

No routine anticoagulation monitoring is required, but:

• Baseline renal function, hepatic function, and complete blood count 2
• Periodic reassessment of renal function, especially in elderly or those with declining kidney function 5
• PT, INR, aPTT, and anti-factor Xa activity testing are not useful for monitoring apixaban effect 1