What are the risks and precautions when using cilostazol with Eliquis (apixaban) in patients?

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From the Guidelines

Combining cilostazol with Eliquis (apixaban) is generally not recommended due to the significantly increased risk of bleeding. Both medications affect blood clotting through different mechanisms - Eliquis is an anticoagulant that directly inhibits factor Xa in the clotting cascade, while cilostazol is an antiplatelet agent that inhibits phosphodiesterase and prevents platelet aggregation 1. When used together, they create a dangerous "double anticoagulant" effect.

The safety and efficacy of combining anticoagulants like apixaban with antiplatelet agents like cilostazol have not been established, according to the American Heart Association 1. If this combination is absolutely necessary, patients require close monitoring for bleeding signs including unusual bruising, nosebleeds, blood in urine or stool, and prolonged bleeding from cuts. Dosage adjustments may be needed, particularly reducing the cilostazol dose while maintaining the prescribed Eliquis regimen.

Some key points to consider when combining these medications include:

  • Regular blood tests to monitor clotting parameters are essential
  • Patients should inform all healthcare providers about this medication combination before any procedures
  • Patients should avoid activities with high injury risk
  • The combination particularly increases risk in elderly patients, those with kidney or liver impairment, history of bleeding disorders, or recent surgery
  • Alternative treatment options should be considered whenever possible to avoid this potentially dangerous drug interaction 1.

It's also important to note that cilostazol has a black-box warning that it should not be used in patients with heart failure, as indicated by the FDA 1. Therefore, the decision to combine cilostazol with Eliquis should be made with caution and careful consideration of the patient's overall health and medical history.

From the Research

Risks and Precautions of Cilostazol with Eliquis (Apixaban)

There are no direct studies on the use of cilostazol with Eliquis (apixaban) in patients. However, the available evidence provides some insights into the potential risks and precautions:

  • Cilostazol is a phosphodiesterase III inhibitor with antiplatelet properties, which may increase the risk of bleeding when combined with anticoagulants like apixaban 2, 3.
  • The use of cilostazol is contraindicated in patients with congestive heart failure, and inhibitors of cytochrome P-450 isoenzymes 3A4 and 2C19 should be used cautiously in patients taking cilostazol 4.
  • Cilostazol has been shown to increase the risk of minor side effects, such as headache, palpitations, and diarrhea, but the frequency of serious adverse events is similar to that of other treatments 5.
  • The clinical applications of cilostazol are expanding, and it has been investigated for use in various settings, including intermittent claudication, coronary artery disease, and prevention of secondary stroke 2, 3.

Clinical Use of Cilostazol

The available evidence suggests that cilostazol is effective in improving symptoms and quality of life in patients with intermittent claudication and peripheral artery disease:

  • Cilostazol has been shown to increase pain-free walking time and total distance walked in patients with intermittent claudication 4, 5.
  • The drug is fairly well tolerated, with the most common adverse effects involving the gastrointestinal tract and central nervous system 4.
  • Cilostazol is underutilized in clinical practice, despite its potential benefits in patients with peripheral artery disease and other conditions 2, 6.

Potential Interactions with Apixaban

While there are no direct studies on the use of cilostazol with apixaban, the available evidence suggests that the combination of these drugs may increase the risk of bleeding:

  • Cilostazol has antiplatelet properties, which may enhance the anticoagulant effect of apixaban and increase the risk of bleeding 2, 3.
  • Patients taking cilostazol and apixaban should be closely monitored for signs of bleeding, and the dosage of these drugs should be adjusted accordingly 4, 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cilostazol: a Review of Basic Mechanisms and Clinical Uses.

Cardiovascular drugs and therapy, 2022

Research

Treatment of intermittent claudication with pentoxifylline and cilostazol.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2001

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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