SELECTED IMPORTANT SAFETY INFORMATION
WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS
INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/
EPIDURAL HEMATOMA
(A) 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.
(B) 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
Monitor patients frequently for signs and symptoms of
neurological impairment. If neurological compromise is noted,
urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention in
patients anticoagulated or to be anticoagulated.
• Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS
undergoing spinal/epidural anesthesia or puncture may develop an epidural
or spinal hematoma which can result in long-term or permanent paralysis.
The risk of these events may be increased by the postoperative use of
indwelling epidural catheters or the concomitant use of medicinal
products affecting hemostasis. Indwelling epidural or intrathecal
catheters should not be removed earlier than 24 hours after the last
administration of ELIQUIS. The next dose of ELIQUIS should not be
administered earlier than 5 hours after the removal of the catheter.
The risk may also be increased by traumatic or repeated epidural or
spinal puncture. If traumatic puncture occurs, delay the administration
of ELIQUIS for 48 hours.
Monitor patients frequently and if neurological compromise is noted, urgent
diagnosis and treatment is necessary. Physicians should consider the
potential benefit versus the risk of neuraxial intervention in ELIQUIS patients.
• Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not
been studied in patients with prosthetic heart valves and is not
recommended in these patients.
• Acute PE in Hemodynamically Unstable Patients or Patients who
Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS
is not recommended as an alternative to unfractionated heparin for the
initial treatment of patients with PE who present with hemodynamic
instability or who may receive thrombolysis or pulmonary embolectomy.
ADVERSE REACTIONS
• The most common and most serious adverse reactions reported with
ELIQUIS were related to bleeding.
TEMPORARY INTERRUPTION FOR SURGERY AND OTHER
INTERVENTIONS
• ELIQUIS should be discontinued at least 48 hours prior to elective
CONTRAINDICATIONS
surgery or invasive procedures with a moderate or high risk of
unacceptable or clinically significant bleeding. ELIQUIS should be
• Active pathological bleeding
discontinued at least 24 hours prior to elective surgery or invasive
• Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)
procedures with a low risk of bleeding or where the bleeding would be
WARNINGS AND PRECAUTIONS
noncritical in location and easily controlled. Bridging anticoagulation
• Increased Risk of Thrombotic Events After Premature Discontinuation:
during the 24 to 48 hours after stopping ELIQUIS and prior to the
Premature discontinuation of any oral anticoagulant, including ELIQUIS,
intervention is not generally required. ELIQUIS should be restarted after
in the absence of adequate alternative anticoagulation increases the
the surgical or other procedures as soon as adequate hemostasis has
risk of thrombotic events. An increased rate of stroke was observed
been established.
during the transition from ELIQUIS to warfarin in clinical trials in atrial
DRUG INTERACTIONS
fibrillation patients. If ELIQUIS is discontinued for a reason other than
• Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of cytochrome
pathological bleeding or completion of a course of therapy, consider
P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) increase exposure to apixaban
coverage with another antico wV