About This Calculator

The Edoxaban Dose Eligibility Calculator is a clinical decision support tool designed for healthcare professionals. It determines the appropriate edoxaban dosage for patients with non-valvular atrial fibrillation (NVAF) to prevent stroke and systemic embolism, and for the treatment of venous thromboembolism (VTE). Dosing recommendations are based on key patient parameters including renal function (Creatinine Clearance), body weight, and the concurrent use of specific P-glycoprotein (P-gp) inhibitors.

Outputs Explained

The tool provides one of the following outputs based on the information entered:

• Recommended Dose: 60 mg Once Daily: This is the standard dose for patients who do not meet any criteria for dose reduction.
• Recommended Dose: 30 mg Once Daily: This reduced dose is recommended if the patient meets one or more of the specified dose reduction criteria. The tool will list the exact reasons for the reduction.
• Edoxaban Is Not Recommended: This output is generated when edoxaban is contraindicated or not recommended based on clinical trial data, such as in patients with severe renal impairment (CrCl < 15 mL/min) or those with NVAF and excellent renal function (CrCl > 95 mL/min).

How to Use the Tool

1. Select Indication: Choose either "Non-valvular Atrial Fibrillation (NVAF)" or "Venous Thromboembolism (VTE) Treatment."
2. Enter Body Weight: Input the patient's actual body weight in kilograms (kg).
3. Provide Renal Function: You can either enter a known Creatinine Clearance (CrCl) value in mL/min or use the integrated Cockcroft-Gault calculator. To calculate, you will need the patient's age, weight, serum creatinine, and sex.
4. Identify P-gp Inhibitor Use: Check the box if the patient is taking any of the listed potent P-glycoprotein inhibitors (e.g., verapamil, dronedarone, quinidine).

The calculator will automatically update the result as you input or change the values.

Dosing Overview

The approved dosing for edoxaban is based on criteria established in the ENGAGE AF-TIMI 48 and Hokusai-VTE clinical trials.

• Standard Dose: 60 mg taken orally once daily.
• Reduced Dose: 30 mg taken orally once daily.

A dose reduction to 30 mg once daily is required if one or more of the following criteria are present:

• Renal Impairment: Creatinine Clearance (CrCl) is between 15 and 50 mL/min.
• Low Body Weight: Body weight is less than or equal to 60 kg.
• Concomitant P-gp Inhibitor Use: The patient is taking verapamil, dronedarone, quinidine, or other specified potent P-gp inhibitors.

Switching Anticoagulants

• From Warfarin to Edoxaban: Discontinue warfarin and initiate edoxaban when the International Normalized Ratio (INR) is ≤ 2.5.
• From other Oral Anticoagulants to Edoxaban: Discontinue the other anticoagulant (e.g., dabigatran, rivaroxaban, apixaban) and start edoxaban at the time of the next scheduled dose of the other agent.
• From Parenteral Anticoagulants to Edoxaban: Discontinue the parenteral agent (e.g., LMWH, UFH) and initiate edoxaban at the time the next scheduled dose of the parenteral anticoagulant would have been due. For continuous UFH infusion, start edoxaban at the time of stopping the infusion.
• From Edoxaban to Warfarin: For continuous dosing, reduce the edoxaban dose to 30 mg and start warfarin concurrently. Once a stable INR of ≥ 2.0 is achieved, discontinue edoxaban.
• From Edoxaban to other Oral Anticoagulants: Discontinue edoxaban and start the other oral anticoagulant at the time of the next scheduled edoxaban dose.

Missed Dose Instructions

If a dose of edoxaban is missed, the patient should take it as soon as possible on the same day. They should then resume their normal once-daily schedule the following day. The patient should not take two doses at the same time to make up for a missed dose.

Safety Alerts

• Reduced Efficacy in NVAF with CrCl > 95 mL/min: Edoxaban is not recommended in patients with NVAF and a CrCl > 95 mL/min. In the ENGAGE AF-TIMI 48 trial, these patients had a higher rate of ischemic stroke with edoxaban 60 mg compared to warfarin.
• Severe Renal Impairment: Edoxaban is not recommended in patients with CrCl < 15 mL/min, as it has not been studied in this population and anticoagulant exposure is expected to be significantly increased.
• Risk of Bleeding: Edoxaban increases the risk of bleeding and can cause serious, potentially fatal, bleeding. Promptly evaluate any signs or symptoms of blood loss.
• Premature Discontinuation: Discontinuing edoxaban prematurely in the absence of adequate alternative anticoagulation increases the risk of thrombotic events.

Frequently Asked Questions

1. Why is CrCl used instead of eGFR for edoxaban dosing?
   The clinical trials that established the safety and efficacy of edoxaban (ENGAGE AF-TIMI 48 and Hokusai-VTE) used the Cockcroft-Gault equation to estimate creatinine clearance for dose adjustments. Therefore, prescribing information recommends using CrCl for dosing decisions.
2. What if a patient meets two or more criteria for dose reduction?
   The dose is reduced to 30 mg once daily if at least one criterion is met. The dose is not further reduced if multiple criteria are present.
3. Does the calculator use actual or ideal body weight for the Cockcroft-Gault calculation?
   The tool uses the single weight value entered, which should be the patient's actual body weight as this was the method used in the landmark trials.
4. My patient has NVAF and their CrCl is 100 mL/min. Why is edoxaban not recommended?
   Clinical trial data showed that patients with NVAF and CrCl > 95 mL/min had a higher rate of ischemic stroke with edoxaban compared to well-managed warfarin. Therefore, alternative anticoagulants should be considered in this population. This warning does not apply to the VTE indication.
5. Can this calculator be used for patients with mechanical heart valves?
   No. Edoxaban, like other direct oral anticoagulants (DOACs), is not recommended for patients with prosthetic mechanical heart valves due to a lack of data and potential for harm.
6. For VTE treatment, is edoxaban started immediately?
   For the treatment of VTE (DVT or PE), patients should receive 5 to 10 days of a parenteral anticoagulant (like heparin or LMWH) first, and then transition to edoxaban.
7. Are there any P-gp inhibitors that do not require an edoxaban dose reduction?
   Yes. While potent inhibitors like verapamil, dronedarone, and quinidine require a dose reduction, others like amiodarone do not, despite being P-gp inhibitors. This tool focuses only on those specified in the prescribing information that mandate a dose change.
8. Is a dose adjustment needed for hepatic impairment?
   No dose adjustment is needed for mild to moderate hepatic impairment. Edoxaban is not recommended in patients with severe hepatic impairment due to coagulopathy and clinically relevant bleeding risk.

References

1. Savaysa® (edoxaban) [Prescribing Information]. Daiichi Sankyo, Inc.
2. Lixiana® (edoxaban) [Summary of Product Characteristics]. European Medicines Agency.
3. Giugliano RP, Ruff CT, Braunwald E, et al. for the ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-2104.
4. Büller HR, Décousus H, Grosso MA, et al. for the Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-1415.