Label Changes for:
Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Reversal of Anticoagulant Effect
- A specific antidote for ELIQUIS is not available, and there is no established way to reverse bleeding in patients taking ELIQUIS. The pharmacodynamic effect of ELIQUIS can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Use of procoagulant reversal agents, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa, may be considered but has not been evaluated in clinical studies. When PCCs are used, monitoring for the anticoagulation effect of apixaban using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity is not useful and is not recommended. Activated oral charcoal reduces absorption of apixaban, thereby lowering apixaban plasma concentration.
USE IN SPECIFIC POPULATIONS
Renal Impairment (revised)
Reduction of Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation
- The recommended dose is 2.5 mg twice daily in patients with at least two of the following characteristics:
- age =80 years
- body weight =60 kg
- serum creatinine =1.5 mg/dL
Patients with End-Stage Renal Disease on Dialysis
- Clinical efficacy and safety studies with ELIQUIS did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of ELIQUIS at the usually recommended dose will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study. It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ARISTOTLE.
Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery, andTreatment of DVT and PE and Reduction in the Risk of Recurrence of DVT and PE
- No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis. Clinical efficacy and safety studies with ELIQUIS did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; therefore, dosing ecommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in subjects with ESRD maintained on dialysis.
PATIENT COUNSELING INFORMATION
Advise patients of the following: (addition of the following)
- How to take ELIQUIS if they cannot swallow, or require a nasogastric tube.
- What to do if a dose is missed.
How should I take ELIQUIS? (addition of the following)
- If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take ELIQUIS.
- *Table 1 (Bleeding events) and Figure 1 modified
USE IN SPECIFIC POPULATIONS
- No dose adjustment is recommended for patients with renal impairment alone, including those with end-stage renal disease (ESRD) maintained on hemodialysis, except nonvalvular atrial fibrillation patients who meet the criteria for dosage adjustment.
- Patients with ESRD (CrCl <15 mL/min) receiving or not receiving hemodialysis were not studied in clinical efficacy and safety studies with ELIQUIS; therefore, the dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-Factor Xa activity) data in subjects with ESRD maintained on dialysis
- No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A). Because patients with moderate hepatic impairment (Child-Pugh class B) may have intrinsic coagulation abnormalities and there is limited clinical experience with ELIQUIS in these patients, dosing recommendations cannot be provided. ELIQUIS is not recommended in patients with severe hepatic impairment (Child-Pugh class C)
WARNING: PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS…
PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of any oral anticoagulant, including Eliquis, increases the risk of thrombotic events. If anticoagulation with Eliquis is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant…
WARNINGS AND PRECAUTIONS
Increased Risk of Thrombotic Events after Premature Discontinuation
- Premature discontinuation of any oral anticoagulant, including Eliquis, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from Eliquis to warfarin in clinical trials in atrial fibrillation patients. If Eliquis is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
8 USE IN SPECIFIC POPULATIONS
8.6 End-Stage Renal Disease Patients Maintained with Hemodialysis
- new subsection added
note: also changes to DOSAGE AND ADMINISTRATION, 2.7 Renal Impairment