Apixaban Contraindications in Cancer Patients
Apixaban is contraindicated in patients with gastric and gastroesophageal cancers due to increased risk of hemorrhage with direct oral anticoagulants (DOACs) in this population. 1
Primary Contraindication: Gastrointestinal Cancers
- Patients with gastric and gastroesophageal tumors are at increased risk for hemorrhage with DOACs including apixaban, making low-molecular-weight heparins (LMWHs) the preferred anticoagulant in this setting 1
- The excess bleeding risk with DOACs is specifically confined to patients with gastrointestinal cancers, as demonstrated in clinical trials 1
- Based on available evidence, patients with gastrointestinal cancer and venous thromboembolism (VTE) should not receive DOACs when other anticoagulant options are available 1
Evidence from Clinical Trials
- In the Hokusai VTE Cancer Study, the absolute rate of major bleeding was 2.9% higher with edoxaban (another DOAC) compared to dalteparin, with the excess bleeding specifically confined to patients with gastrointestinal cancer 1
- While the Caravaggio study showed comparable major bleeding rates between apixaban and dalteparin overall (3.8% vs 4.0%), the NCCN panel still recommends caution with apixaban in gastric/gastroesophageal cancer patients 1, 2
- The International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee specifically advises against using DOACs in patients with gastrointestinal cancer when other anticoagulant options are available 1
Other Relative Contraindications
- Severe renal impairment (CrCl <15 ml/min) - DOACs including apixaban are contraindicated in this population 1
- Patients receiving potent inhibitors or inducers of CYP3A4 and P-glycoprotein - these may significantly alter apixaban plasma levels 1
- Triple-positive antiphospholipid syndrome - DOACs including apixaban are contraindicated in this condition 1
Special Considerations for Other Cancer Types
- Brain tumors: While historically considered high-risk for anticoagulant-associated intracranial hemorrhage, recent evidence suggests apixaban may be safe in this population 1, 3
- A retrospective study comparing DOACs versus LMWH for VTE treatment in patients with primary brain tumors found no significant difference in 6-month cumulative bleeding events, including intracranial hemorrhage (14.3% vs 27.8%, P=0.10) 1
- Apixaban was associated with a greater reduction in major bleeding risk among brain cancer patients (HR = 0.32) compared to those with other cancer types (HR = 0.72) when compared to LMWH 3
Practical Recommendations
- For patients with gastric or gastroesophageal cancers requiring anticoagulation, use LMWH as first-line therapy instead of apixaban 1
- For patients with other cancer types, apixaban is generally safe and effective, with the NCCN panel assigning a category 1 recommendation based on high-quality evidence 1
- Monitor closely for drug-drug interactions in cancer patients receiving apixaban, particularly with antimitotic microtubule inhibitors, tyrosine kinase inhibitors, and immunomodulating agents including glucocorticoids 1
- When transitioning between anticoagulants, consult specific prescribing information for appropriate protocols 1
Dosing Considerations
- Standard apixaban dosing for cancer-associated VTE treatment is 10 mg twice daily for 7 days followed by 5 mg twice daily 2
- For primary VTE prevention in high-risk cancer patients, a lower dose of 2.5 mg twice daily has been studied 1, 4
- Dose adjustment may be necessary in patients with multiple risk factors for bleeding 1