About

The Apixaban Dose Eligibility calculator helps clinicians determine the appropriate dosing schedule for apixaban (Eliquis®) in patients with nonvalvular atrial fibrillation (NVAF) for the prevention of stroke and systemic embolism. The guidance is based on the specific dose modification criteria used in the pivotal ARISTOTLE clinical trial.

Outputs

The dosing recommendation is based on whether a patient meets at least two of the three established criteria for dose reduction. The possible outputs are:

• Standard Dose (5 mg twice daily): Recommended for most patients with NVAF who do not meet the criteria for a dose reduction.
• Reduced Dose (2.5 mg twice daily): Recommended for patients who meet at least two of the following three criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.

How to Use

The determination of apixaban dosing in NVAF requires assessing three key patient parameters. A dose reduction is warranted if a patient satisfies at least two of these criteria.

1. Assess Age: Determine if the patient's age is 80 years or older.
2. Assess Body Weight: Determine if the patient's body weight is 60 kilograms (approximately 132 pounds) or less.
3. Assess Serum Creatinine (SCr): Determine if the patient's serum creatinine level is 1.5 mg/dL (133 µmol/L) or greater.

If two or more of the above conditions are true, the patient is eligible for the reduced apixaban dose of 2.5 mg twice daily. Otherwise, the standard 5 mg twice daily dose is indicated.

Dosing Overview

The recommended dosing for apixaban varies by indication. The criteria discussed here apply specifically to stroke prevention in nonvalvular atrial fibrillation.

• Nonvalvular Atrial Fibrillation: The standard dose is 5 mg orally twice daily. A reduced dose of 2.5 mg twice daily is recommended for patients with at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.
• Treatment of DVT/PE: 10 mg orally twice daily for 7 days, followed by 5 mg orally twice daily.
• Prophylaxis of Recurrent DVT/PE: 2.5 mg orally twice daily after at least 6 months of treatment.
• VTE Prophylaxis (Post-Knee/Hip Replacement): 2.5 mg orally twice daily.

Note: The dose reduction criteria for NVAF do not apply to other indications.

Switching

Switching from Warfarin to Apixaban

Discontinue warfarin and initiate apixaban when the patient's International Normalized Ratio (INR) is below 2.0.

Switching from Apixaban to Warfarin

Discontinue apixaban and begin both a parenteral anticoagulant and warfarin at the time of the next scheduled apixaban dose. Discontinue the parenteral anticoagulant once INR reaches a therapeutic range.

Switching from other Anticoagulants

When switching from other oral anticoagulants (e.g., rivaroxaban, dabigatran) or parenteral anticoagulants (e.g., heparin, enoxaparin) to apixaban, discontinue the current agent and begin apixaban at the time of the next scheduled dose.

Missed Dose

If a dose of apixaban is missed, the patient should take it as soon as they remember on the same day. They should then resume their regular twice-daily schedule. The patient should not take two doses at the same time to make up for a missed dose.

Safety Alerts

Apixaban has a boxed warning regarding two key safety concerns:

• Premature Discontinuation: Discontinuing apixaban prematurely increases the risk of thrombotic events, such as stroke. If anticoagulation with apixaban must be discontinued for reasons other than pathological bleeding, consider coverage with another anticoagulant.
• Spinal/Epidural Hematoma: Patients receiving neuraxial anesthesia (spinal or epidural) or undergoing spinal puncture are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis.

Apixaban is contraindicated in patients with active pathological bleeding or severe hypersensitivity.

FAQ

What are the specific criteria for apixaban dose reduction in NVAF?

A reduced dose (2.5 mg twice daily) is recommended if a patient meets at least two of these three criteria: age 80 years or older, body weight 60 kg or less, and serum creatinine 1.5 mg/dL or higher.

Why is renal function (serum creatinine) important for apixaban dosing?

Apixaban is partially cleared by the kidneys. Impaired renal function can lead to increased drug levels and a higher risk of bleeding, which is why a high serum creatinine level is one of the criteria for considering a dose reduction.

Does this calculator apply to patients on dialysis?

No. The use of apixaban is generally not recommended in patients with a creatinine clearance (CrCl) of less than 15 mL/min or in those on dialysis due to limited clinical data. The ARISTOTLE trial excluded these patients.

Can I use these criteria for dosing apixaban for DVT or PE treatment?

No. The dose reduction criteria (age, weight, SCr) are only validated for stroke prevention in nonvalvular atrial fibrillation. Dosing for VTE (DVT/PE) treatment or prophylaxis follows a different schedule and does not use these criteria.

What happens if only one criterion for dose reduction is met?

If only one criterion is met (e.g., a patient is 82 years old but has a weight of 70 kg and SCr of 1.1 mg/dL), the standard dose of 5 mg twice daily is recommended.

Is it necessary to calculate Creatinine Clearance (CrCl)?

While the dose reduction criteria are based on serum creatinine, the official prescribing information also provides dosing guidance based on CrCl for patients with end-stage renal disease. For the specific NVAF dose reduction criteria, only the absolute SCr value is needed.

What if a patient's weight fluctuates around 60 kg?

Clinical judgment is required. Dosing decisions should be based on a stable, recent weight. If there is uncertainty, regular monitoring and re-evaluation are advised.

Does mild or moderate liver impairment affect apixaban dosing?

No dosage adjustment is needed for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Apixaban is not recommended in patients with severe hepatic impairment (Child-Pugh C).

References

1. Eliquis® (apixaban) Prescribing Information. U.S. Food and Drug Administration. Revised: 04/2021.
2. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992. doi:10.1056/NEJMoa1107039 (ARISTOTLE Trial).
3. Bristol Myers Squibb. Eliquis (apixaban) Dosing & Administration. Official Manufacturer HCP site. Accessed October 2023.
4. National Institute for Health and Care Excellence (NICE). Apixaban - NICE British National Formulary. Accessed October 2023.