`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`202155Orig1s000
`
`
`REMS
`
`
`
`
`
`Initial REMS Approval Date: 12/2012
`
`
`NDA 202155
`ELIQUIS® (apixaban) tablets
`
`Factor Xa Inhibitor
`
`Bristol-Myers Squibb Company
`Research & Development
`777 Scudders Mill Road
`Plainsboro, NJ 08536
`United States of America
`
`Contact Information:
`Phone: 609-897-5854
`Fax: 609-897-3627
`
`
`
`
`I.
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS)
`
`
`GOAL
`
`The goal of the ELIQUIS REMS is to inform healthcare providers (HCPs) about:
`
`
`the increased risk of thrombotic events, including stroke, in patients with nonvalvular
`atrial fibrillation when discontinuing ELIQUIS without introducing an adequate
`alternative anticoagulant
`the importance of following the recommendations in the US Prescribing Information
`(USPI) on how to convert patients with nonvalvular atrial fibrillation from ELIQUIS
`to warfarin or other anticoagulants.
`REMS ELEMENTS
`Communication Plan
`
`A.
`
`
`
`II.
`
`Bristol-Myers Squibb will implement a communication plan to HCPs to support
`implementation of this REMS.
`
`
`
` 1
`
`Reference ID: 3237516
`
`
`
`
`
`
`1. Dear Healthcare Professional Letter
`A Dear Healthcare Professional (DHCP) Letter will be distributed by direct mail or
`electronic delivery to HCPs including: cardiologists, neurologists, emergency medicine
`physicians, internal medicine physicians, primary care physicians, nurse practitioners,
`physician assistants, and pharmacists. The letter will be distributed within 60 days of
`approval of ELIQUIS. Annual letters will be sent within 60 days of the anniversary date
`of approval for ELIQUIS every year for two additional years and within 60 days of FDA
`approval of any substantial safety update. The DHCP Letter will also be provided to FDA
`MedWatch at these times. A copy of the USPI and Medication Guide will accompany the
`DHCP Letter.
`In addition, the DHCP Letter, USPI and Medication Guide will also be available on the
`ELIQUIS REMS website and upon request.
`The DHCP letter is part of the REMS and is appended.
`2. ELIQUIS REMS Website
`Within 30 days of REMS approval, Bristol-Myers Squibb will post information for HCPs
`and patients on the ELIQUIS REMS website (http://www.ELIQUISREMS.com). This
`information will remain on the website for a period of 2 years.
`The content of the print or web-based material will include the following:
`
` Goal of the REMS
`
`Information about the risk
` US Prescribing Information for ELIQUIS
` Medication Guide for ELIQUIS
` DHCP Letter (for a period of 2 years)
`The ELIQUIS REMS website is part of the REMS and is appended.
`3. Letters to Professional Organizations
`A Professional Organization Letter will be distributed by direct mail or electronic
`delivery within 60 days of the REMS approval date. This communication to professional
`organizations will include the same information as that contained in the DHCP Letter.
`Bristol-Myers Squibb will request that these organizations disseminate this information to
`their members. Bristol-Myers Squibb will communicate the letter to the leadership of the
`following professional organizations:
`
`
`2
`
`Reference ID: 3237516
`
`
`
`
`
`
` American Heart Association (AHA)
`
` American College of Cardiologists (ACC)
`
` Heart Rhythm Society (HRS)
`
` Society for Cardiovascular Angiography and Interventions (SCAI)
`
` American Academy of Neurology (AAN)
`
` American Neurological Association (ANA)
`
` National Institute of Neurological Disorders and Stroke (NINDS)
`
` American Stroke Association (ASA)
`
` National Stroke Association (NSA)
`
` American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM)
`
` Association of Emergency Physicians (AEP)
`
` American College of Chest Physicians (ACCP)
`
` Association of Black Cardiologists (ABC)
`
` American Academy of Family Physicians (AAFP)
`
` American College of Physicians (ACP)
`
` Society of General Internal Medicine (SGIM)
`
` National Medical Association (NMA)
`
` American Academy of Nurse Practitioners (AANP)
`
` American Academy of Physician Assistants (AAPA)
`
` American College of Clinical Pharmacy (ACCP)
`
` American Society of Health-System Pharmacists (ASHP)
`
` American Pharmacists Association (APhA)
`
`
`
`3
`
`Reference ID: 3237516
`
`
`
`
`
`
` National Association of Chain Drug Stores (NACDS)
`
` American Association of Critical-Care Nurses (AACN)
`
` National Association of Clinical Nurse Specialists (NACNS)
`
`The USPI and the Medication Guide will be provided in conjunction with the letter.
`The Professional Organization Letter is part of the REMS and is appended.
`
`
`B.
`
`Timetable for Submission of Assessments
`
`Bristol-Myers Squibb will submit REMS Assessments to the FDA at 18 months, 3 years,
`and 7 years from the date of the REMS approval. To facilitate inclusion of as much
`information as possible while allowing reasonable time to prepare the submission, the
`reporting interval covered by each assessment should conclude no earlier than 60 days
`before the submission date for that assessment. Bristol-Myers Squibb will submit each
`assessment so that it will be received by the FDA on or before the due date.
`
`
`
`4
`
`Reference ID: 3237516
`
`
`
`[Insert Month DD, YEAR]
`
`
`IMPORTANT DRUG WARNING
`ELIQUIS® (apixaban) tablets
`
`
`Discontinuing ELIQUIS without introducing an adequate alternative
`anticoagulant places nonvalvular atrial fibrillation patients at an increased risk of
`thrombotic events, including stroke
`
`Subject:
`
`
`Dear Healthcare Professional:
`information for
`important safety
`inform you of
`to
`is
`The purpose of
`this
`letter
`ELIQUIS (apixaban). ELIQUIS is an oral, reversible factor Xa inhibitor indicated to reduce the
`risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
`The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to
`ensure that the benefits of ELIQUIS outweigh the potential risks in patients with nonvalvular
`atrial fibrillation including:
`
`Increased risk of thrombotic events, including stroke, when discontinuing ELIQUIS
`without an adequate alternative anticoagulant
`
`
`Please read the recommendations in the US Prescribing Information (USPI) on how to
`convert patients with nonvalvular atrial fibrillation from ELIQUIS to warfarin or other
`anticoagulants.
`
`The ELIQUIS® labeling includes a BOXED WARNING to highlight the safety issue of
`increased risk of thrombotic events following discontinuation of ELIQUIS®.
`
`
`WARNING: DISCONTINUING ELIQUIS IN PATIENTS WITHOUT ADEQUATE
`CONTINUOUS ANTICOAGULATION INCREASES RISK OF STROKE
`
`
`Discontinuing ELIQUIS places patients at an increased risk of thrombotic events. An increased
`rate of stroke was observed following discontinuation of ELIQUIS in clinical trials in patients
`with nonvalvular atrial fibrillation. If anticoagulation with ELIQUIS must be discontinued for a
`reason other than pathological bleeding, coverage with another anticoagulant should be strongly
`considered.
`
`
`Reference ID: 3237516
`
`
`1
`
`
`
`Increased Risk of Stroke with Discontinuation of ELIQUIS
`ELIQUIS has an apparent half-life of 12 hours during repeat dosing, therefore, the anticoagulant
`effect of ELIQUIS is present when the drug is taken and for at least a day after discontinuation.
`Discontinuing 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 patients with nonvalvular atrial fibrillation. If ELIQUIS
`must be discontinued for a reason other than pathological bleeding, consider coverage with
`another anticoagulant.
`Patient Counseling
`Advise patients to take ELIQUIS only as directed and not to discontinue ELIQUIS without first
`speaking to you.
`Medication Guide
`The Medication Guide contains information to support patient counseling regarding the risks and
`benefits of treatment with ELIQUIS. Additional copies of the ELIQUIS Medication Guide may
`be obtained from:
` Bristol-Myers Squibb toll-free line at 1-855-354-7847
`
`the ELIQUIS REMS website at http://www.ELIQUISREMS.com
`
`Reporting Adverse Events
`To report all suspected adverse events associated with the use of ELIQUIS, please contact:
` Bristol-Myers Squibb at 1-800-721-5072 and/or
` FDA Medwatch Program at 1-800-FDA-1088 or www.fda.gov/medwatch.
`For more information regarding ELIQUIS, please contact the Medical Information department at
`1-800-321-1335 or visit the website at www.ELIQUIS.com.
`This letter is not intended as a comprehensive description of risks associated with the use of
`ELIQUIS. Please read the accompanying USPI, including Medication Guide, for a complete
`description of these risks.
`
`Sincerely,
`
`
`[Click here to enter names of signatories]
`Enclosure: ELIQUIS USPI with Medication Guide
` [BMS Corporate logo] [Pfizer Inc logo]
`2012 Bristol-Myers Squibb Company
`
`
`
`432US12REMS00101
`
`12/12
`
`Reference ID: 3237516
`
`
`2
`
`
`
`IMPORTANT DRUG WARNING
`Eliquis® (apixaban) tablets
`
`Distribute this Information to Your Members
`
`
`[Insert Month DD, YEAR]
`Dear Professional Organization:
`information for
`important safety
`inform you of
`to
`is
`The purpose of
`this
`letter
`ELIQUIS (apixaban). ELIQUIS is an oral, reversible factor Xa inhibitor indicated to reduce the
`risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
`The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to
`ensure that the benefits of ELIQUIS outweigh the potential risks in patients with nonvalvular
`atrial fibrillation including:
`
`Increased risk of thrombotic events, including stroke, when discontinuing ELIQUIS
`without an adequate alternative anticoagulant
`
`
`Please read the recommendations in the US Prescribing Information (USPI) on how to
`convert patients with nonvalvular atrial fibrillation from ELIQUIS to warfarin or other
`anticoagulants.
`
`The ELIQUIS® labeling includes a BOXED WARNING to highlight the safety issue of
`increased risk of thrombotic events following discontinuation of ELIQUIS®.
`
`
`WARNING: DISCONTINUING ELIQUIS IN PATIENTS WITHOUT ADEQUATE
`CONTINUOUS ANTICOAGULATION INCREASES RISK OF STROKE
`
`
`Discontinuing ELIQUIS places patients at an increased risk of thrombotic events. An increased
`rate of stroke was observed following discontinuation of ELIQUIS in clinical trials in patients
`with nonvalvular atrial fibrillation. If anticoagulation with ELIQUIS must be discontinued for a
`reason other than pathological bleeding, coverage with another anticoagulant should be strongly
`considered.
`
`
`
`
` 1
`
`Reference ID: 3237516
`
`
`
`Increased Risk of Stroke with Discontinuation of ELIQUIS
`ELIQUIS has an apparent half-life of 12 hours during repeat dosing, therefore, the anticoagulant
`effect of ELIQUIS is present when the drug is taken and for at least a day after discontinuation.
`Discontinuing 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 patients with nonvalvular atrial fibrillation. If ELIQUIS
`must be discontinued for a reason other than pathological bleeding, consider coverage with
`another anticoagulant.
`Patient Counseling
`Advise patients to take ELIQUIS only as directed and not to discontinue ELIQUIS without first
`speaking to you.
`Medication Guide
`The Medication Guide contains information to support patient counseling regarding the risks and
`benefits of treatment with ELIQUIS. Additional copies of the ELIQUIS Medication Guide may
`be obtained from:
` Bristol-Myers Squibb toll-free line at 1-855-354-7847
`
`the ELIQUIS REMS website at http://www.ELIQUISREMS.com
`
`Reporting Adverse Events
`To report all suspected adverse events associated with the use of ELIQUIS, please contact:
` Bristol-Myers Squibb at 1-800-721-5072 and/or
` FDA Medwatch Program at 1-800-FDA-1088 or www.fda.gov/medwatch.
`For more information regarding ELIQUIS, please contact the Medical Information department at
`1-800-321-1335 or visit the website at www.ELIQUIS.com.
`This letter is not intended as a comprehensive description of risks associated with the use of
`ELIQUIS. Please read the accompanying USPI, including Medication Guide, for a complete
`description of these risks.
`
`Sincerely,
`
`
`[Click here to enter names of signatories]
`Enclosure: ELIQUIS USPI with Medication Guide
` [BMS Corporate logo] [Pfizer Inc logo]
`2012 Bristol-Myers Squibb Company
`
`432US12REMS00401
`
`12/12
`
`
`
`
`
` 2
`
`Reference ID: 3237516
`
`
`
`Reference ID: 3237516
`
`930066035
`
`2.0
`
`3.0
`
`Approved
`
`v
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROBERT TEMPLE
`12/28/2012
`
`Reference ID: 3237516
`
`
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