Side Effects of Apixaban (Eliquis)
The most significant side effect of apixaban is bleeding, which can range from minor bruising to major hemorrhagic events, with intracranial hemorrhage being less common compared to warfarin but still a serious concern. 1, 2
Common Side Effects
Bleeding-related complications:
Non-bleeding side effects:
- Skin rash
- Allergic reactions (rare but potentially severe)
- Symptoms of allergic reactions may include 1:
- Chest pain or tightness
- Swelling of face or tongue
- Trouble breathing or wheezing
- Feeling dizzy or faint
Risk Factors for Bleeding
Several factors increase the risk of bleeding when taking apixaban:
History of previous bleeding (increases odds of bleeding by 17.62 times) 5
Higher trough plasma levels of apixaban 5
Concomitant use of other medications that increase bleeding risk 6:
- Antiplatelet agents (aspirin, clopidogrel)
- NSAIDs
- SSRIs or SNRIs
Renal impairment (apixaban is approximately 27% renally cleared) 3, 7
Hepatic impairment 3
Advanced age (≥80 years)
Low body weight (≤60 kg)
Elevated serum creatinine (≥1.5 mg/dL) 8
Comparative Safety Profile
Apixaban has demonstrated a more favorable bleeding profile compared to warfarin:
- Lower rates of major bleeding (2.13% vs 3.09% per year) 3
- Significantly reduced risk of intracranial hemorrhage (0.24% vs 0.47% per year) 3
- Less adverse consequences following extracranial hemorrhage 2
In the ARISTOTLE trial, apixaban was superior to warfarin in preventing stroke and systemic embolism while producing less bleeding 3.
Special Populations and Considerations
- Renal impairment: Apixaban should be avoided in patients with severe renal impairment (CrCl <15 mL/min) 3, 6
- Hepatic impairment: Not recommended in patients with significant liver dysfunction (transaminases >2 times upper limit of normal or total bilirubin >1.5 times upper limit of normal) 3
- Pregnancy and lactation: Not recommended during pregnancy or breastfeeding 1
- Drug interactions: Strong inhibitors of both CYP3A4 and P-glycoprotein (e.g., ketoconazole, ritonavir) can significantly increase apixaban plasma concentrations 6
Monitoring and Management
- Regular assessment for signs of bleeding is essential 6
- Monitor renal and hepatic function periodically 6
- Consider dose reduction (2.5 mg twice daily instead of standard 5 mg twice daily) for patients with at least two of: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 3, 8
- In case of major bleeding, consider specific reversal agents like prothrombin complex concentrates 6
- Do not abruptly discontinue apixaban without medical supervision due to increased risk of thrombotic events 3
Clinical Implications
When prescribing apixaban, healthcare providers should:
- Assess bleeding risk before initiating therapy
- Educate patients about signs and symptoms of bleeding
- Instruct patients to inform all healthcare providers about apixaban use before any procedures
- Consider proton pump inhibitors to reduce gastrointestinal bleeding risk in high-risk patients 6
- Ensure appropriate dosing based on patient characteristics
Understanding these side effects and risk factors allows for appropriate patient selection and monitoring, maximizing the benefits of apixaban while minimizing risks.