CardioSource WorldNews September 2015 | Page 2

SELECTED IMPORTANT SAFETY INFORMATION (CONT’D)
WARNING: (B) SPINAL/EPIDURAL HEMATOMA
(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 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
surgery or invasive procedures with a moderate or high risk of
unacceptable or clinically significant bleeding. ELIQUIS should be
discontinued at least 24 hours prior to elective surgery or invasive
CONTRAINDICATIONS
procedures with a low risk of bleeding or where the bleeding would be
noncritical in location and easily controlled. Bridging anticoagulation
• Active pathological bleeding
during the 24 to 48 hours after stopping ELIQUIS and prior to the
• Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)
intervention is not generally required. ELIQUIS should be restarted after
WARNINGS AND PRECAUTIONS
the surgical or other procedures as soon as adequate hemostasis has
• Increased Risk of Thrombotic Events After Premature Discontinuation:
been established.
Premature discontinuation of any oral anticoagulant, including ELIQUIS,
DRUG INTERACTIONS
in the absence of adequate alternative anticoagulation increases the
• Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of cytochrome
risk of thrombotic events. An increased rate of stroke was observed
P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) increase exposure to apixaban
during the transition from ELIQUIS to warfarin in clinical trials in atrial
and increase the risk of bleeding. For patients receiving ELIQUIS doses of
fibrillation patients. If ELIQUIS is discontinued for a reason other than
5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when
pathological bleeding or completion of a course of therapy, consider
ELIQUIS is coadministered with drugs that are strong dual inhibitors of
coverage with another anticoagulant.
CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or
• Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause
clarithromycin). In patients already taking 2.5 mg twice daily, avoid
serious, potentially fatal, bleeding.
coadministration of ELIQUIS with strong dual inhibitors of CYP3A4 and P-gp.
– Concomitant use of drugs affecting hemostasis increases the risk of
• Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of
bleeding, including aspirin and other antiplatelet agents, other
ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin,
anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and
carbamazepine, phenytoin, St. John’s wort) because such drugs will
NSAIDs.
decrease exposure to apixaban and increase the risk of stroke and other
– Advise patients of signs and symptoms of blood loss and to report
thromboembolic events.
them immediately or go to an emergency room. Discont inue ELIQUIS
• Anticoagulants and Antiplatelet Agents: Coadministration of
in patients with active pathological hemorrhage.
antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use
– There is no established way to reverse the anticoagulant effect of
increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical
apixaban, which can be expected to persist for at least 24 hours after
trial of apixaban in high-risk post-acute coronary syndrome patients
the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS
treated with aspirin or the combination of aspirin and clopidogrel, was
is not available.
terminated early due to a higher rate of bleeding with apixaban
• Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS
compared to placebo.
undergoing spinal/epidural anesthesia or puncture may develop an epidural PREGNANCY CATEGORY B
or spinal hematoma which can result in long-term or permanent paralysis.
• There are no adequate and well-controlled studies of ELIQUIS in
The risk of these events may be increased by the postoperative use of
pregnant women. Treatment is likely to increase the risk of hemorrhage
indwelling epidural catheters or the concomitant use of medicinal
during pregnancy and delivery. ELIQUIS should be used during
products affecting hemostasis. Indwelling epidural or intrathecal
pregnancy only if the potential benefit outweighs the potential risk to
catheters should not be removed earlier than 24 hours after the last
the mother and fetus.
administration of ELIQUIS. The next dose of ELIQUIS should not be
administered earlier than 5 hours after the removal of the catheter.
Please see Brief Summary of Full Prescribing Information, including
The risk may also be increased by traumatic or repeated epidural or
Boxed WARNINGS, on the adjacent pages.

ELIQUIS® and the ELIQUIS logo are trademarks of Bristol-Myers Squibb Company.
© 2015 Bristol-Myers Squibb Company. All rights reserved. 432US15BR00771-02-01 08/15