What are the potential interactions between Celebrex (celecoxib) and Xarelto (rivaroxaban)?

From the Guidelines

Taking Celebrex (celecoxib) and Xarelto (rivaroxaban) together is generally not recommended due to an increased risk of bleeding, and this combination should be avoided unless specifically directed by your healthcare provider with careful monitoring. Both medications can affect blood clotting through different mechanisms: Xarelto is an anticoagulant that directly inhibits clotting factor Xa, while Celebrex is a nonsteroidal anti-inflammatory drug (NSAID) that can reduce platelet aggregation and irritate the stomach lining. When used together, they can significantly increase bleeding risk, particularly in the gastrointestinal tract, as noted in studies such as 1 which discusses the potential interactions between rivaroxaban and other drugs, including NSAIDs like celecoxib.

The potential for increased bleeding risk is a significant concern, and patients should be closely monitored if they are taking both medications. According to 1, the management of bleeding in patients on oral anticoagulants like rivaroxaban involves careful consideration of the risks and benefits of different treatment strategies. The use of andexanet alfa, a recombinant protein that binds FXa inhibitors, may be considered in cases of major bleeding, as discussed in 1. However, the primary concern is to minimize the risk of bleeding by avoiding the combination of Celebrex and Xarelto unless absolutely necessary.

If you must take both medications, it is essential to watch for warning signs of bleeding, such as unusual bruising, nosebleeds, blood in urine or stool, or coffee-ground vomit. The risk is higher in older adults, those with kidney problems, or patients with a history of stomach ulcers, as noted in 1, which discusses the use of nonsteroidal anti-inflammatory drugs and their potential risks. Never stop either medication suddenly without medical guidance, as this could lead to serious complications related to your underlying conditions.

Key considerations for healthcare providers include:

• Carefully weighing the benefits and risks of using Celebrex and Xarelto together
• Closely monitoring patients for signs of bleeding
• Considering alternative treatment strategies to minimize the risk of bleeding
• Providing patients with clear guidance on the risks and benefits of their medication regimen, as discussed in 1 and 1.

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 The potential interaction between Celebrex (celecoxib), an NSAID, and Xarelto (rivaroxaban) is an increased risk of bleeding.

• Key points:
  • Concomitant use of NSAIDs and XARELTO may increase the risk of bleeding.
  • The pharmacokinetics of rivaroxaban are not affected by NSAIDs, such as naproxen or aspirin. 2

From the Research

Potential Interactions between Celebrex and Xarelto

The potential interactions between Celebrex (celecoxib) and Xarelto (rivaroxaban) are a concern due to the increased risk of bleeding.

• Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that can increase the risk of bleeding, especially when combined with anticoagulants like rivaroxaban 3.
• Rivaroxaban is a direct oral anticoagulant (DOAC) that works by inhibiting factor Xa, and its anticoagulant effect can be enhanced by concomitant use of NSAIDs like celecoxib 3.
• A study found that coadministration of rivaroxaban and the NSAID naproxen significantly increased bleeding time, although the difference between major and clinically relevant nonmajor bleeding was not significantly different between NSAID users and nonusers in a retrospective analysis of large trials 3.

Management of Bleeding Risk

To manage the bleeding risk associated with concomitant use of celecoxib and rivaroxaban:

• Monitoring of patients for signs of bleeding is crucial, especially in those with a history of bleeding disorders or concomitant use of other medications that increase the risk of bleeding 4, 5.
• The use of specific reversal agents, such as andexanet alfa, may be considered in patients with life-threatening or uncontrolled bleeding due to rivaroxaban 5.
• Nonspecific strategies, including supplementation of clotting factors with prothrombin complex concentrates (PCCs) or activated PCCs, may also be used to attenuate anticoagulation effects in patients with major bleeding 5.

Cardiovascular Risk

The cardiovascular risk associated with celecoxib is a concern, as it has been shown to increase the risk of myocardial infarction and serious vascular events compared to placebo 6.

• However, the risk of cardiovascular events associated with celecoxib is small in absolute terms, and the benefits of the drug may outweigh the potential adverse effects on the cardiovascular system 6.
• The concomitant use of celecoxib and rivaroxaban may increase the risk of bleeding, but the cardiovascular risk associated with celecoxib should also be considered when making treatment decisions 6.