What is the interaction between Rivaroxaban (Xarelto) and Ibuprofen?

From the Guidelines

Taking Rivaroxaban (Xarelto) and Ibuprofen together is not recommended due to increased bleeding risk, and alternative pain relief options such as acetaminophen (Tylenol) should be considered. The interaction between Rivaroxaban and Ibuprofen is a concern because Rivaroxaban is an anticoagulant that prevents blood clots by inhibiting Factor Xa in the clotting cascade, while Ibuprofen reduces blood clotting ability by inhibiting platelets and prostaglandin production. Although the provided study 1 does not specifically examine the interaction between Rivaroxaban and Ibuprofen, it does investigate the interaction between Rivaroxaban and another nonsteroidal anti-inflammatory drug (NSAID), naproxen. The study found that the concomitant administration of Rivaroxaban and naproxen resulted in a significant increase in bleeding time and a slight increase in plasma concentrations of Rivaroxaban.

Given the similar mechanism of action of Ibuprofen and naproxen, it is reasonable to assume that the combination of Rivaroxaban and Ibuprofen may also increase the risk of bleeding. The study 1 also examined the interaction between Rivaroxaban and aspirin, which is another antiplatelet agent, and found that the combination of Rivaroxaban and aspirin prolonged bleeding time more than aspirin alone.

Key points to consider when taking Rivaroxaban and Ibuprofen together include:

• Increased bleeding risk, including potentially serious gastrointestinal bleeding
• Alternative pain relief options, such as acetaminophen (Tylenol), should be considered
• If Ibuprofen must be taken, dosing schedule may need to be adjusted, and closer monitoring may be necessary
• Stomach-protecting medications may be prescribed to reduce the risk of gastrointestinal bleeding
• Signs of bleeding, such as unusual bruising, nosebleeds, blood in urine or stool, or severe headache, should be reported to a healthcare provider immediately.

From the FDA Drug Label

NSAIDs/Aspirin In ROCKET AF, concomitant aspirin use (almost exclusively at a dose of 100 mg or less) during the double-blind phase was identified as an independent risk factor for major bleeding. NSAIDs are known to increase bleeding, and bleeding risk may be increased when NSAIDs are used concomitantly with XARELTO Neither naproxen nor aspirin affected the pharmacokinetics of rivaroxaban (see Figure 3)

The interaction between Rivaroxaban (Xarelto) and Ibuprofen is not directly addressed in the provided drug label. However, it is mentioned that NSAIDs, a class of drugs that includes ibuprofen, are known to increase bleeding, and bleeding risk may be increased when NSAIDs are used concomitantly with XARELTO.

• Bleeding risk may be increased when ibuprofen is used with XARELTO.
• The pharmacokinetics of rivaroxaban may not be affected by NSAIDs, as seen with naproxen. 2

From the Research

Interaction between Rivaroxaban and Ibuprofen

There are no direct studies provided that examine the interaction between Rivaroxaban (Xarelto) and Ibuprofen. However, some studies provide information on the interaction between Rivaroxaban and other medications, which may be relevant:

• The study 3 mentions that combination with other antithrombotic drugs should be avoided, but does not specifically mention Ibuprofen.
• The study 4 discusses the combined use of anticoagulation plus antiplatelet agents, including the use of rivaroxaban with aspirin, but does not mention Ibuprofen.
• The study 5 examines the effect of proton pump inhibitors on the risk of gastrointestinal bleeding in patients with atrial fibrillation treated with oral anticoagulants, including rivaroxaban, but does not mention Ibuprofen.
• The study 6 analyzes real-world data of patients prescribed rivaroxaban and apixaban, but does not mention Ibuprofen.
• The study 7 discusses the role of rivaroxaban in atrial fibrillation and acute coronary syndromes, including its use with aspirin, but does not mention Ibuprofen.

Key Points

• There is no direct evidence provided on the interaction between Rivaroxaban and Ibuprofen.
• Rivaroxaban should be used with caution when combined with other medications, especially antithrombotic drugs.
• Proton pump inhibitors may be used to reduce the risk of gastrointestinal bleeding in patients taking rivaroxaban.
• The use of rivaroxaban with aspirin has been studied, but the interaction with Ibuprofen is not well understood based on the provided evidence.