Does initiating diclofenac (Voltaren) gel increase the risk of bleeding in a patient taking Xarelto (rivaroxaban)?

From the Guidelines

There is a minimal increased bleeding risk when using diclofenac gel while on Xarelto (rivaroxaban). Topical NSAIDs like diclofenac gel are generally considered safe to use with anticoagulants because they have limited systemic absorption compared to oral NSAIDs. The small amount of diclofenac that enters the bloodstream from topical application is unlikely to significantly interact with Xarelto or substantially increase bleeding risk, as supported by studies on the pharmacokinetics of rivaroxaban and its interactions with other drugs 1.

Some key points to consider when using diclofenac gel with Xarelto include:

• The potential for increased bleeding risk is lower with topical NSAIDs compared to oral NSAIDs, as seen in studies where the concomitant administration of rivaroxaban with naproxen, an oral NSAID, resulted in a significant increase in bleeding time 1.
• Patients should still use the gel as directed, applying it only to intact skin and avoiding excessive use over large areas of the body.
• They should monitor for any unusual bruising or bleeding and report these symptoms to their healthcare provider.
• If the patient needs pain relief for an extended period, they should consult their healthcare provider to ensure the combination remains appropriate for their specific situation.

The theoretical concern stems from NSAIDs' ability to affect platelet function, which could potentially add to the anticoagulant effect of Xarelto, but this risk is considerably lower with topical versus oral NSAID formulations. As noted in the study on the concomitant administration of rivaroxaban and aspirin, the combination of anticoagulants and antiplatelet agents can increase bleeding risk, but the effect of topical NSAIDs like diclofenac gel is expected to be minimal 1.

From the FDA Drug Label

Concomitant use of other drugs that impair hemostasis increases the risk of bleeding These include ... non-steroidal anti-inflammatory drugs (NSAIDs)

• Key words: increased risk of bleeding, NSAIDs
• The patient is on Xarelto, which increases the risk of bleeding.
• Diclofenac gel is a topical NSAID, and while it may have a lower risk of bleeding compared to oral NSAIDs, the FDA label does not provide specific information on the risk of bleeding with concomitant use of Xarelto and diclofenac gel.
• However, considering the general warning about the increased risk of bleeding with concomitant use of Xarelto and NSAIDs, it is reasonable to assume that there may be an increased bleeding risk with the use of diclofenac gel in a patient on Xarelto.
• Main idea: The concomitant use of Xarelto and diclofenac gel may increase the risk of bleeding, although the exact risk is not specified in the FDA label 2.

From the Research

Increased Bleeding Risk with Xarelto and Diclofenac Gel

• The studies provided do not directly address the increased bleeding risk with patients on Xarelto who begin using diclofenac gel 3, 4, 5, 6.
• However, it is known that Xarelto (rivaroxaban) is an anticoagulant that increases the risk of bleeding, and diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that can also increase the risk of bleeding 7.
• A study on the long-term treatment with the combination of rivaroxaban and aspirin in patients with chronic coronary or peripheral artery disease found that the incidence rates for major and minor bleeding were 1.01 and 2.49 per 100 patient years, respectively 7.
• Another study on the safety and efficacy of topical diclofenac sodium 1% gel in knee osteoarthritis found that treatment-related adverse events were infrequent, with application site dermatitis being the most common adverse event, and no treatment-related gastrointestinal or serious adverse events occurred 6.
• The interaction between Xarelto and diclofenac gel is not explicitly studied in the provided evidence, but it is possible that the combination may increase the risk of bleeding due to the anticoagulant and anti-inflammatory properties of the two medications 3, 4, 5, 6, 7.

Key Findings

• Diclofenac gel is effective in relieving pain and improving function in patients with knee osteoarthritis 3, 6.
• The combination of rivaroxaban and aspirin increases the risk of bleeding, but the incidence rates for major and minor bleeding are relatively low 7.
• Topical diclofenac has a lower risk of gastrointestinal adverse events compared to oral NSAIDs 3, 6.
• The safety and efficacy of diclofenac gel in patients on Xarelto is not directly addressed in the provided studies, and further research is needed to determine the potential risks and benefits of this combination 3, 4, 5, 6, 7.