From the Guidelines
Apixaban does not require gastric acid for absorption, whereas rivaroxaban requires an acidic environment for optimal absorption, particularly at higher doses. The absorption of apixaban is not significantly affected by changes in gastric pH, and it can be taken without regard to food or antacid medications 1. In contrast, the 15mg and 20mg doses of rivaroxaban should be taken with food to enhance absorption, as food increases the area under the curve (AUC) plasma concentrations by 39% 1. Some key points to consider when prescribing these medications include:
- The bioavailability of rivaroxaban is 66% without food and 80-100% with food, whereas apixaban has a bioavailability of 50% regardless of food intake 1.
- Rivaroxaban has a higher plasma protein binding (95%) compared to apixaban (87%) 1.
- The elimination half-life of apixaban is 12 hours, whereas rivaroxaban has an elimination half-life of 5-9 hours in young patients and 11-13 hours in elderly patients 1. It is essential to consider these differences in absorption and pharmacokinetics when prescribing apixaban or rivaroxaban to patients, especially those taking proton pump inhibitors, H2 blockers, or antacids, as reduced rivaroxaban absorption may compromise its anticoagulant effect 1.
From the FDA Drug Label
Since rivaroxaban absorption is dependent on the site of drug release, avoid administration of XARELTO distal to the stomach which can result in reduced absorption and thereby, reduced drug exposure. The FDA drug label for rivaroxaban does not explicitly state that gastric acid is required for absorption. However, it does indicate that the site of drug release is important for absorption, and administration distal to the stomach can result in reduced absorption.
- There is no information about apixaban in the provided label.
- The label only discusses rivaroxaban, and its absorption is dependent on the site of release, but it does not directly address the need for gastric acid 2.
From the Research
Absorption of Apixaban and Rivaroxaban
- The absorption of apixaban and rivaroxaban is dependent on the intestinal P-glycoprotein (P-gp) system, but it is not directly dependent on gastric acid 3.
- Studies have shown that concomitant medication with proton pump inhibitors (PPIs) can increase the bioavailability of rivaroxaban, but the effect on apixaban is not well established 3, 4.
- The use of PPIs as co-therapy with oral anticoagulants, including apixaban and rivaroxaban, can reduce the risk of major gastrointestinal bleeding (GIB) in patients with atrial fibrillation and a prior history of upper GIB 5, 4.
Effect of Gastrointestinal Tract Surgery on Absorption
- Major gastrointestinal tract surgery can affect the absorption of direct-acting oral anticoagulants (DOACs), including apixaban and rivaroxaban 6, 7.
- Patients who underwent gastrectomy or duodenum and proximal jejunum exclusion had lower peak plasma concentrations of rivaroxaban, while those who underwent distal bowel or ileostomy had peak rivaroxaban plasma concentrations within the effective range 7.
- Apixaban peak concentrations were less affected by gastrointestinal tract surgery, with most patients achieving effective peak concentrations regardless of the type of surgery 7.
Clinical Implications
- Clinicians should be aware of the potential effects of gastrointestinal tract surgery on the absorption of DOACs, including apixaban and rivaroxaban 6, 7.
- The use of PPIs as co-therapy with oral anticoagulants may reduce the risk of major GIB, but the effect on apixaban and rivaroxaban absorption is not well established 5, 4.
- Further studies are needed to fully understand the effects of gastrointestinal tract surgery and PPI co-therapy on the absorption and efficacy of apixaban and rivaroxaban 3, 6, 7.