When is a dose reduction of Elquis (apixaban) considered?

From the Guidelines

A dose reduction of Elquis (apixaban) to 2.5 mg twice daily is recommended if a patient meets at least two of the following criteria: age 80 years or older, body weight 60 kg (132 lbs) or less, or serum creatinine 1.5 mg/dL or higher, as stated in the 2021 ACC expert consensus decision pathway 1. This dose reduction is necessary to minimize the risk of bleeding complications while maintaining the efficacy of apixaban in preventing thrombosis. The criteria for dose reduction are based on the patient's age, body weight, and renal function, as these factors can affect the clearance of apixaban and increase the risk of bleeding. Some key points to consider when reducing the dose of apixaban include:

• Age: Patients 80 years or older may require a dose reduction due to decreased renal function and increased sensitivity to the drug 1.
• Body weight: Patients with a body weight of 60 kg (132 lbs) or less may require a dose reduction due to increased sensitivity to the drug 1.
• Renal function: Patients with severe renal impairment (creatinine clearance 15-29 mL/min) should receive the reduced dose of 2.5 mg twice daily 1.
• Concomitant medications: Patients taking strong dual inhibitors of CYP3A4 and P-glycoprotein, such as ketoconazole, itraconazole, ritonavir, or clarithromycin, may require a dose reduction due to increased apixaban levels 1. It is essential to carefully evaluate each patient's individual characteristics and medical history to determine the appropriate dose of apixaban, as stated in the 2016 ESC guidelines for the management of atrial fibrillation 1 and the 2012 American Heart Association/American Stroke Association science advisory 1.

From the FDA Drug Label

For patients receiving apixaban tablets doses of 5 mg or 10 mg twice daily, reduce the dose by 50% when apixaban tablet is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3)]. In patients already taking 2. 5 mg twice daily, avoid coadministration of apixaban tablets with combined P-glycoprotein (P-gp) and strong CYP3A4 inhibitors [see Drug Interactions (7.1)].

A dose reduction of Elquis (apixaban) is considered in the following situations:

• When coadministered with combined P-gp and strong CYP3A4 inhibitors, the dose should be reduced by 50% for patients taking 5 mg or 10 mg twice daily.
• For patients already taking 2.5 mg twice daily, coadministration with combined P-gp and strong CYP3A4 inhibitors should be avoided 2. Key points:
• Dose reduction is necessary to minimize the risk of bleeding when apixaban is coadministered with certain drugs.
• The dose reduction is specific to the coadministration of combined P-gp and strong CYP3A4 inhibitors.

From the Research

Dose Reduction of Elquis (Apixaban)

A dose reduction of Elquis (apixaban) is considered in certain patient populations, including:

• Patients with chronic kidney disease stage 4 and 5, including those on hemodialysis 3
• Patients with advanced renal impairment, although the optimal dose in these patients is not well established and should be made on a patient-specific basis 3, 4
• Patients aged 80 years or older, weighing 60 kg or less, and having a serum creatinine level of 1.5 mg/dL or higher, who may be eligible for a reduced dose of apixaban 5

Patient-Specific Factors

The decision to reduce the dose of apixaban should take into account the following patient-specific factors:

• Age: patients aged 80 years or older may be eligible for a reduced dose 5
• Weight: patients weighing 60 kg or less may be eligible for a reduced dose 5
• Renal function: patients with advanced renal impairment, including those on hemodialysis, may require a reduced dose 3, 4, 6, 7
• Serum creatinine level: patients with a serum creatinine level of 1.5 mg/dL or higher may be eligible for a reduced dose 5

Clinical Evidence

Clinical studies have shown that apixaban is effective and safe in patients with atrial fibrillation and advanced chronic kidney disease, including those on hemodialysis 6, 7. However, the optimal dose of apixaban in these patients is not well established and requires further study 3, 4. A meta-analysis of observational studies found that apixaban was associated with a lower risk of major bleeding compared to warfarin in patients with advanced chronic kidney disease or end-stage renal disease 7.