ELIQUIS® (apixaban) tablets for oral use
Brief Summary of Prescribing Information. For complete prescribing information
consult official package insert.
WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK
OF THROMBOTIC EVENTS
(B) SPINAL/EPIDURAL HEMATOMA
(A) 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 [see Dosage
and Administration, Warnings and Precautions, and Clinical Studies (14.1) in
full Prescribing Information].
(B) SPINAL/EPIDURAL HEMATOMA
Epidural or spinal hematomas may occur in patients treated with ELIQUIS
who are receiving neuraxial anesthesia or undergoing spinal puncture. These
hematomas may result in long-term or permanent paralysis. Consider these
risks when scheduling patients for spinal procedures. Factors that can increase
the risk of developing epidural or spinal hematomas in these patients include:
• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as nonsteroidal
anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
• a history of traumatic or repeated epidural or spinal punctures
• a history of spinal deformity or spinal surgery
• optimal timing between the administration of ELIQUIS and neuraxial
procedures is not known
[see Warnings and Precautions]
Monitor patients frequently for signs and symptoms of neurological impairment.
If neurological compromise is noted, urgent treatment is necessary [see
Warnings and Precautions].
Consider the benefits and risks before neuraxial intervention in patients
anticoagulated or to be anticoagulated [see Warnings and Precautions].
ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of
the prescribing information.
•
Increased risk of thrombotic events after premature discontinuation [see Warnings
and Precautions]
•
Bleeding [see Warnings and Precautions]
•
Spinal/epidural anesthesia or puncture [see Warnings and Precautions]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation
The safety of ELIQUIS (apixaban) was evaluated in the ARISTOTLE and AVERROES studies
[see Clinical Studies (14) in full Prescribing Information], including 11,284 patients exposed
to ELIQUIS 5 mg twice daily and 602 patients exposed to ELIQUIS 2.5 mg twice daily.
The duration of ELIQUIS exposure was ≥12 months for 9375 patients and ≥24 months
for 3369 patients in the two studies. In ARISTOTLE, the mean duration of exposure was
89 weeks (>15,000 patient-years). In AVERROES, the mean duration of exposure was
approximately 59 weeks (>3000 patient-years).
The most common reason for treatment discontinuation in both studies was for bleedingrelated adverse reactions; in ARISTOTLE this occurred in 1.7% and 2.5% of patients treated
with ELIQUIS and warfarin, respectively, and in AVERROES, in 1.5% and 1.3% on ELIQUIS
and aspirin, respectively.
Bleeding in Patients with Nonvalvular Atrial Fibrillation in ARISTOTLE and AVERROES
Tables 1 and 2 show the number of patients experiencing major bleeding during the
treatment period and the bleeding rate (percentage of subjects with at least one bleeding
event per year) in ARISTOTLE and AVERROES.
Major bleeding was defined as clinically overt bleeding that was accompanied by one or more
of the following: a decrease in hemoglobin of 2 g/dL or more; a transfusion of 2 or more
units of packed red blood cells; bleeding that occurred i