Side Effects of Eliquis (Apixaban)
Bleeding is the primary side effect of Eliquis, with major bleeding occurring at a rate of 2.13% per year, though this is significantly lower than warfarin (3.09% per year). 1
Major Bleeding Risks
Gastrointestinal Bleeding
- Gastrointestinal bleeding is the most common site of major bleeding with apixaban, occurring at a rate of 0.89% per 100 patient-years. 2
- The FDA label specifically identifies gastrointestinal bleeding as a potential side effect. 3, 4
- Rates of GI bleeding were similar between apixaban and warfarin in the ARISTOTLE trial. 1
Intracranial Hemorrhage
- Apixaban has a significantly lower risk of intracranial bleeding compared to warfarin (0.24% vs 0.47% per year; HR 0.51). 1
- Hemorrhagic stroke rates are reduced by approximately 49% compared to warfarin. 1
- Intracranial bleeding rates with apixaban are similar to aspirin (0.33% vs 0.40% per 100 patient-years). 2
Severity and Outcomes
- Most major bleeding events are nonemergencies characterized by hemoglobin drops ≥2 g/dL requiring transfusion. 2
- Fatal bleeding occurs at a rate of 0.10% per 100 patient-years. 2
- Apixaban-associated major bleeds are less likely to occur at critical sites (27.9%) compared to aspirin (46.8%). 2
Allergic Reactions
Severe allergic reactions can occur and require immediate medical attention. 4
The FDA label specifies watching for:
- Chest pain or tightness 4
- Swelling of face or tongue 4
- Trouble breathing or wheezing 4
- Feeling dizzy or faint 4
- Skin rash 4
Risk Factors That Increase Bleeding
Patient-Specific Factors
- NSAID use increases major bleeding risk by over 10-fold (HR 10.25). 2
- Active cancer increases bleeding risk nearly 3-fold (HR 2.87). 2
- Advanced age (≥75 years) increases susceptibility to adverse effects, with each 5-year increase conferring HR 1.47 for major bleeding. 3, 2
- History of bleeding or active bleeding. 1
- Concurrent antiplatelet therapy. 1
- Renal impairment (27% renal elimination may lead to higher drug levels). 1, 3
Drug Interactions
- Medications affecting CYP3A4 or P-glycoprotein pathways can alter apixaban levels and increase bleeding risk. 3
- Concurrent use of antiplatelets or other anticoagulants. 1
Dosing Errors and Inappropriate Use
Underdosing
- Apixaban has the highest rates of underdosing among DOACs (9.4-40.4%). 1
- Paradoxically, underdosed patients experienced more bleeding events (5.9%) than appropriately dosed patients (2.3%) in one study, likely because underdosing occurs in patients with perceived high bleeding risk. 1
Overdosing
- Overdosing occurred in 14.3-34.1% of hospitalized patients. 1
- All bleeding events in one study occurred in overdosed patients. 1
Contraindications and Precautions
Do not use apixaban if you have: 4
- Active pathological bleeding 4
- Severe renal impairment (CrCl <15 mL/min) 1, 3
- Severe hepatic impairment (transaminases >2× ULN or bilirubin >1.5× ULN) 1, 3
Clinical Context
The overall safety profile of apixaban is favorable compared to warfarin, with 31% reduction in major bleeding and 11% reduction in all-cause mortality in the ARISTOTLE trial. 1 However, when combined with dual antiplatelet therapy in acute coronary syndrome patients, the APPRAISE-2 trial was stopped early due to excess bleeding, including intracranial hemorrhage, without evidence of efficacy. 1
Key pitfall: Avoid combining apixaban with dual antiplatelet therapy outside of carefully selected circumstances, as this dramatically increases bleeding risk without clear benefit. 1