`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`203214Orig1s000
`
`
`REMS
`
`

`

`
`
`REMS
`
`GOAL
`
`NDA 203,214 XELJANZ® (TOFACITINIB)
`
`Pfizer Inc
`235 East 42nd St
`NY, NY 10017
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS)
`
`The goal of the XELJANZ REMS is to inform healthcare providers and patients about the
`serious risks associated with XELJANZ treatment.
`
`
`REMS ELEMENTS:
`
`Medication Guide
`
`In accordance with 21 CFR 208.24, a Medication Guide will be included in each XELJANZ
`package. This Medication Guide should be dispensed to each patient by the pharmacy with each
`XELJANZ prescription. The Medication Guide will also be available via sales representatives,
`the XELJANZ patient and professional websites, the XELJANZ REMS website, and a toll-free
`product information line. The Medication Guide is enclosed in Appendix I.
`
`Communication Plan
`
`Pfizer Inc will implement a communication plan to the following healthcare providers:
`
` Rheumatologists and rheumatology healthcare providers (including physician assistants
`and nurse practitioners) who are likely to prescribe XELJANZ,
`
`
`
`Infectious disease specialists who may be consulted about and treat serious infections
`including herpes zoster, tuberculosis and other opportunistic infections,
`
` Family practitioners, general practitioners, and internal medicine specialists who may be
`consulted about and be involved in treating serious infections, decreases in neutrophil
`counts, decrease in lymphocyte counts, decreases in hemoglobin, and lipid elevations and
`hyperlipidaemia,
`
` Emergency medicine specialists who may evaluate and treat serious infections including
`herpes zoster, and tuberculosis and other opportunistic infections in emergency care
`settings, and
`
` Pharmacists who will dispense XELJANZ.
`
`
`
`Reference ID: 3213422
`
`1
`
`

`

`
`
`Elements of the communication plan include the following:
`
`1. A Dear Healthcare Provider Letter will be distributed twice annually for three years to
`rheumatologists and rheumatology healthcare providers (including physician assistants
`and nurse practitioners), infectious disease specialists, family practitioners, general
`practitioners, internal medicine specialists, and emergency medicine specialists through
`both traditional mailing and electronic mailing. This letter will be distributed within 60
`days of product approval. The Dear Healthcare Provider letter is enclosed in Appendix A.
`
`The Prescribing Information and a copy of the Medication Guide will also be distributed
`in this communication.
`
`2. A Dear Pharmacist letter will be distributed to pharmacists twice annually for three years
`through both traditional mailing and electronic mailing. This letter will be distributed
`within 60 days of product approval. The Dear Pharmacist Letter is enclosed in
`Appendix B.
`
`3. Dissemination of information about the known and potential serious risks associated with
`XELJANZ will be made to healthcare providers through certain professional societies’
`scientific meetings and journals.
`o Display journal information pieces, for two years following product approval, as a
`panel/poster and distribution as printed material at major convention meetings of
`rheumatologists and other healthcare professionals specializing in rheumatology
`where the company has a sponsored booth (e.g., American College of
`Rheumatology, Congress of Clinical Rheumatology, and American Society of
`Health System Pharmacists annual meetings).
`o Quarterly, for three years following product approval, presentation as a printed
`information piece in The Rheumatologist, Arthritis &Rheumatism, Arthritis Care
`& Research, Clinical Infectious Disease, Annals of Emergency Medicine,
`American Family Physician, Annals of Internal Medicine, American Journal of
`Health-System Pharmacy, and Journal of the Academy of Managed Care
`Pharmacy. The drafts of the important drug warning that will be printed in the
`aforementioned scientific journals are enclosed in Appendices C through
`Appendix G.
`
`
`
`4. Pfizer will ensure that all materials listed in or appended to the XELJANZ REMS
`program will be available through the XELJANZ REMS program website
`www.XELJANZREMS.com. The XELJANZ REMS program website will exist for
`3 years following approval of the REMS. The landing page for the XELJANZ REMS
`website is appended (see Appendix H).
`
`2
`
`
`
`
`
`Reference ID: 3213422
`
`

`

`
`
`Timetable for Submission of Assessments
`
`Pfizer will submit REMS Assessments to the FDA at 18 months, by 3 years and 7 years from the
`date of approval of the REMS (XX-XX-2012). 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. Pfizer will submit each assessment so that it will be received by the FDA on or
`before the due date.
`
`
`
`
`
`Reference ID: 3213422
`
`3
`
`

`

`
`
`
`Appendix A: Dear HealthCare Provider Letter
`
`
`
`November 2012
`
`
`Subject:
`
`IMPORTANT DRUG WARNING
`
`Risk of serious infections, malignancies, decreases in peripheral lymphocyte
`counts, neutrophil counts, hemoglobin, and increases in lipid parameters in
`peripheral blood with XELJANZ® (tofacitinib)
`
`
`Dear Healthcare Provider,
`
`The purpose of this letter is to inform you of important safety information for XELJANZ®
`(tofacitinib citrate), an inhibitor of Janus kinases (JAKs) approved by the Food and Drug
`Administration (FDA) for adult patients with moderately to severely active rheumatoid arthritis
`(RA) who have had an inadequate response or intolerance to methotrexate. It may be used as
`monotherapy or in combination with methotrexate or other nonbiologic disease-modifying
`antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`Patient Counseling
`You must discuss the risks associated with XELJANZ therapy with patients and in applicable
`instances with their caregivers.
`
`FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary for
`XELJANZ to ensure that the benefits of the drug outweigh the potential risks.
`
`Serious Risks of XELJANZ® (tofacitinib)
`
`Serious Infections
`
`
` Patients treated with XELJANZ are at increased risk for developing serious infections
`leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. Most
`patients who developed these infections were taking concomitant immunosuppressants
`such as methotrexate or corticosteroids.
`
`
`
`Reference ID: 3213422
`
`4
`
`

`

`
`
` XELJANZ should not be initiated in patients with an active infection, including localized
`infections. If a serious infection develops, XELJANZ should be interrupted until the
`infection is controlled.
`
` Prior to initiating XELJANZ, a test for latent TB should be performed. If the test is
`positive, treatment for TB should be started prior to starting XELJANZ. All patients
`should be monitored for active TB during treatment, including patients who tested
`negative for latent TB prior to initiating therapy.
`Malignancies and Lymphoproliferative Disorder
`
`
` Consider the risks and benefits of XELJANZ treatment prior to initiating therapy in
`patients with a known malignancy other than a successfully treated non-melanoma skin
`cancer (NMSC) or when considering continuing XELJANZ in patients who develop a
`malignancy. Lymphoma and other malignancies have been reported in patients treated
`with XELJANZ.
`
`
`
`
`
`In the seven controlled rheumatoid arthritis clinical studies, 11 solid cancers and one
`lymphoma were diagnosed in 3328 patients receiving XELJANZ with or without
`DMARD, compared to 0 solid cancers and 0 lymphomas in 809 patients in the placebo
`with or without DMARD group during the first 12 months of exposure. Lymphomas and
`solid cancers have also been observed in the long-term extension studies in rheumatoid
`arthritis patients treated with XELJANZ.
`
`In Phase 2B, controlled dose-ranging studies in de-novo renal transplant patients, all of
`whom received induction therapy with basiliximab, high dose corticosteroids, and
`mycophenolic acid products, Epstein Barr Virus-associated post-transplant
`lymphoproliferative disorder was observed in 5 out of 218 patients treated with
`XELJANZ (2.3%) compared to 0 out of 111 patients treated with cyclosporine.
`
`
`Important Information on Laboratory Abnormalities
`
`
` Lymphocytes, neutrophils, hemoglobin, and lipids should be monitored, as abnormalities
`in these parameters were associated with XELJANZ treatment in Phase 3 clinical trials.
`
`Medication Guide
`The Medication Guide contains information that can be used to facilitate discussions about the
`known and potential risks of therapy. A copy is enclosed. The XELJANZ Medication Guide
`must be provided to patients being treated with XELJANZ or to their caregiver at the time of
`first dose or if the Medication Guide is materially changed. Additional copies of the Medication
`Guide may be obtained from the XELJANZ REMS web site (www.XELJANZREMS.com) or by
`calling Pfizer at 1-800-438-1985.
`
`
`
`
`Reference ID: 3213422
`
`5
`
`

`

`
`
`Reporting Adverse Events
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`This letter is not a comprehensive description of the risks associated with the use of XELJANZ.
`Please read the accompanying full Prescribing Information, including Boxed Warning, and
`Medication Guide for a complete description of these risks.
`
`For more information, please call Pfizer Medical Information at 1-800-438-1985 or visit the
`XELJANZ REMS web site (www.XELJANZREMS.com).
`
`
`Sincerely,
`
`
`
`Chief Medical Officer
`Pfizer
`
`Enclosure
`
`
`
`
`Reference ID: 3213422
`
`6
`
`

`

`
`
`
`Appendix B: Dear Pharmacist Letter
`
`November 2012
`
`
`
`
`IMPORTANT DRUG WARNING
`
`
`
`Dear Pharmacist,
`
`The purpose of this letter is to inform you of important safety information for XELJANZ®
`(tofacitinib citrate), an inhibitor of Janus kinases (JAKs) approved by the Food and Drug
`Administration (FDA) for adult patients with moderately to severely active rheumatoid arthritis
`(RA) who have had an inadequate response or intolerance to methotrexate. It may be used as
`monotherapy or in combination with methotrexate or other nonbiologic disease-modifying
`antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary for
`XELJANZ to ensure that the benefits of the drug outweigh the potential risks.
`
`Serious Risks of XELJANZ® (tofacitinib)
`
`Serious Infections
`
`
` Patients treated with XELJANZ are at increased risk for developing serious infections
`leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. Most
`patients who developed these infections were taking concomitant immunosuppressants
`such as methotrexate or corticosteroids.
`
` XELJANZ should not be initiated in patients with an active infection, including localized
`infections. If a serious infection develops, XELJANZ should be interrupted until the
`infection is controlled.
`
` Prior to initiating XELJANZ, a test for latent TB should be performed. If the test is
`positive, treatment for TB should be started prior to starting XELJANZ. All patients
`should be monitored for active TB during treatment, including patients who tested
`negative for latent TB prior to initiating therapy.
`
`
`
`Reference ID: 3213422
`
`7
`
`

`

`
`
`Malignancies and Lymphoproliferative Disorder
`
`
` Consider the risks and benefits of XELJANZ treatment prior to initiating therapy in
`patients with a known malignancy other than a successfully treated non-melanoma skin
`cancer (NMSC) or when considering continuing XELJANZ in patients who develop a
`malignancy. Lymphoma and other malignancies have been reported in patients treated
`with XELJANZ.
`
`
`
`
`
`In the seven controlled rheumatoid arthritis clinical studies, 11 solid cancers and one
`lymphoma were diagnosed in 3328 patients receiving XELJANZ with or without
`DMARD, compared to 0 solid cancers and 0 lymphomas in 809 patients in the placebo
`with or without DMARD group during the first 12 months of exposure. Lymphomas and
`solid cancers have also been observed in the long-term extension studies in rheumatoid
`arthritis patients treated with XELJANZ.
`
`In Phase 2B, controlled dose-ranging studies in de-novo renal transplant patients, all of
`whom received induction therapy with basiliximab, high dose corticosteroids, and
`mycophenolic acid products, Epstein Barr Virus-associated post-transplant
`lymphoproliferative disorder was observed in 5 out of 218 patients treated with
`XELJANZ (2.3%) compared to 0 out of 111 patients treated with cyclosporine.
`
`
`Important Information on Laboratory Abnormalities
`
`
` Lymphocytes, neutrophils, hemoglobin, and lipids should be monitored, as abnormalities
`in these parameters were associated with XELJANZ treatment in Phase 3 clinical trials.
`
`Medication Guide
`The FDA requires that a copy of the enclosed XELJANZ Medication Guide be distributed to
`patients who receive XELJANZ or to their caregiver at the time of dispensing or if the
`Medication Guide is materially changed. Additional copies of the Medication Guide may be
`obtained from the XELJANZ REMS web site (www.XELJANZREMS.com) or by calling Pfizer
`at 1-800-438-1985.
`
`Reporting Adverse Events
`
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`This letter is not a comprehensive description of the risks associated with the use of XELJANZ.
`Please read the accompanying full Prescribing Information, including Boxed Warning, and
`Medication Guide for a complete description of these risks.
`
`
`
`
`Reference ID: 3213422
`
`8
`
`

`

`
`
`For more information, please call Pfizer Medical Information at 1-800-438-1985 or visit the
`XELJANZ REMS web site (www.XELJANZREMS.com).
`
`
`Sincerely,
`
`
`
`Chief Medical Officer
`Pfizer
`
`Enclosure
`
`
`
`
`Reference ID: 3213422
`
`9
`
`

`

`
`
`
`Appendix C: Journal Information Piece For Rheumatologists or Rheumatology
`Healthcare Providers (including physician assistants and nurse practitioners)
`
`Important Drug Warning for Rheumatologists and Rheumatology Healthcare Providers
`(including physician assistants and nurse practitioners) about Risks and Potential Risks
`with XELJANZ
`
`XELJANZ® (tofacitinib citrate) is an inhibitor of Janus kinases (JAKs) approved by the Food
`and Drug Administration (FDA) for adult patients with moderately to severely active rheumatoid
`arthritis (RA) who have had an inadequate response or intolerance to methotrexate. It may be
`used as monotherapy or in combination with methotrexate or other nonbiologic disease-
`modifying antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice
`daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`Serious Risks of XELJANZ® (tofacitinib)
`Serious Infections: Patients treated with XELJANZ are at increased risk for developing serious
`infections leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. XELJANZ should
`not be initiated in patients with an active infection, including localized infections. If a serious
`infection develops, XELJANZ should be interrupted until the infection is controlled.
`
`Malignancies and Lymphoproliferative Disorder: Consider the risks and benefits of
`XELJANZ treatment prior to initiating therapy in patients with a known malignancy other than a
`successfully treated non-melanoma skin cancer (NMSC) or when considering continuing
`XELJANZ in patients who develop a malignancy. Lymphoma and other malignancies have been
`reported in patients treated with XELJANZ.
`
`Laboratory Abnormalities: Lymphocytes, neutrophils, hemoglobin, and lipids should be
`monitored, as abnormalities in these parameters were associated with XELJANZ treatment in
`Phase 3 clinical trials. Please see the full Prescribing Information for more information.
`
`Reporting Adverse Events
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`
`
`
`Reference ID: 3213422
`
`10
`
`

`

`
`
`This is not a comprehensive representation of the potential risks associated with use of
`XELJANZ. For a complete description of these potential risks, please visit the XELJANZ REMS
`web site (www.XELJANZREMS.com) for Full Prescribing Information and Medication Guide.
`
`
`
`Reference ID: 3213422
`
`11
`
`

`

`
`
`
`Appendix D: Journal Information Piece For Infectious Disease Specialists
`
`Important Drug Warning for Infectious Disease Specialists about Risks and Potential Risks
`with XELJANZ
`
`XELJANZ® (tofacitinib citrate) is an inhibitor of Janus kinases (JAKs) approved by the Food
`and Drug Administration (FDA) for adult patients with moderately to severely active rheumatoid
`arthritis (RA) who have had an inadequate response or intolerance to methotrexate. It may be
`used as monotherapy or in combination with methotrexate or other nonbiologic disease-
`modifying antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice
`daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`Serious Risks of XELJANZ® (tofacitinib)
`Serious Infections: Patients treated with XELJANZ are at increased risk for developing serious
`infections leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. XELJANZ should
`not be initiated in patients with an active infection, including localized infections. If a serious
`infection develops, XELJANZ should be interrupted until the infection is controlled.
`
`Malignancies and Lymphoproliferative Disorder: Consider the risks and benefits of
`XELJANZ treatment prior to initiating therapy in patients with a known malignancy other than a
`successfully treated non-melanoma skin cancer (NMSC) or when considering continuing
`XELJANZ in patients who develop a malignancy. Lymphoma and other malignancies have been
`reported in patients treated with XELJANZ.
`
`Laboratory Abnormalities: Lymphocytes, neutrophils, hemoglobin, and lipids should be
`monitored, as abnormalities in these parameters were associated with XELJANZ treatment in
`Phase 3 clinical trials. Please see the full Prescribing Information for more information.
`
`Reporting Adverse Events
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`This is not a comprehensive representation of the potential risks associated with use of
`XELJANZ. For a complete description of these potential risks, please visit the XELJANZ REMS
`web site (www.XELJANZREMS.com) for Full Prescribing Information and Medication Guide.
`
`
`
`Reference ID: 3213422
`
`12
`
`

`

`
`
`Appendix E: Journal Information Piece For Family Practitioners, General Practitioners,
`and Internal Medicine Specialists
`
`Important Drug Warning for Family Practitioners, General Practitioners, and Internal
`Medicine Specialists about Risks and Potential Risks with XELJANZ
`
`XELJANZ® (tofacitinib citrate) is an inhibitor of Janus kinases (JAKs) approved by the Food
`and Drug Administration (FDA) for adult patients with moderately to severely active rheumatoid
`arthritis (RA) who have had an inadequate response or intolerance to methotrexate. It may be
`used as monotherapy or in combination with methotrexate or other nonbiologic disease-
`modifying antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice
`daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`Serious Risks of XELJANZ® (tofacitinib)
`Serious Infections: Patients treated with XELJANZ are at increased risk for developing serious
`infections leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. XELJANZ should
`not be initiated in patients with an active infection, including localized infections. If a serious
`infection develops, XELJANZ should be interrupted until the infection is controlled.
`
`Malignancies and Lymphoproliferative Disorder: Consider the risks and benefits of
`XELJANZ treatment prior to initiating therapy in patients with a known malignancy other than a
`successfully treated non-melanoma skin cancer (NMSC) or when considering continuing
`XELJANZ in patients who develop a malignancy. Lymphoma and other malignancies have been
`reported in patients treated with XELJANZ.
`
`Laboratory Abnormalities: Lymphocytes, neutrophils, hemoglobin, and lipids should be
`monitored, as abnormalities in these parameters were associated with XELJANZ treatment in
`Phase 3 clinical trials. Please see the full Prescribing Information for more information.
`
`Reporting Adverse Events
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`This is not a comprehensive representation of the potential risks associated with use of
`XELJANZ. For a complete description of these potential risks, please visit the XELJANZ REMS
`web site (www.XELJANZREMS.com) for Full Prescribing Information and Medication Guide.
`
`
`
`Reference ID: 3213422
`
`13
`
`

`

`
`
`
`Appendix F: Journal Information Piece For Emergency Medicine Specialists
`
`Important Drug Warning for Emergency Medicine Specialists about Risks and Potential
`Risks with XELJANZ
`
`XELJANZ® (tofacitinib citrate) is an inhibitor of Janus kinases (JAKs) approved by the Food
`and Drug Administration (FDA) for adult patients with moderately to severely active rheumatoid
`arthritis (RA) who have had an inadequate response or intolerance to methotrexate. It may be
`used as monotherapy or in combination with methotrexate or other nonbiologic disease-
`modifying antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice
`daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`Serious Risks of XELJANZ® (tofacitinib)
`Serious Infections: Patients treated with XELJANZ are at increased risk for developing serious
`infections leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. XELJANZ should
`not be initiated in patients with an active infection, including localized infections. If a serious
`infection develops, XELJANZ should be interrupted until the infection is controlled.
`
`Malignancies and Lymphoproliferative Disorder: Consider the risks and benefits of
`XELJANZ treatment prior to initiating therapy in patients with a known malignancy other than a
`successfully treated non-melanoma skin cancer (NMSC) or when considering continuing
`XELJANZ in patients who develop a malignancy. Lymphoma and other malignancies have been
`reported in patients treated with XELJANZ.
`
`Laboratory Abnormalities: Lymphocytes, neutrophils, hemoglobin, and lipids should be
`monitored, as abnormalities in these parameters were associated with XELJANZ treatment in
`Phase 3 clinical trials. Please see the full Prescribing Information for more information.
`
`Reporting Adverse Events
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`This is not a comprehensive representation of the potential risks associated with use of
`XELJANZ. For a complete description of these potential risks, please visit the XELJANZ REMS
`web site (www.XELJANZREMS.com) for Full Prescribing Information and Medication Guide.
`
`
`
`Reference ID: 3213422
`
`14
`
`

`

`
`
`Appendix G: Journal Information Piece For Pharmacists
`
`Important Drug Warning for Pharmacists about Risks and Potential Risks with XELJANZ
`
`XELJANZ® (tofacitinib citrate) is an inhibitor of Janus kinases (JAKs) approved by the Food
`and Drug Administration (FDA) for adult patients with moderately to severely active rheumatoid
`arthritis (RA) who have had an inadequate response or intolerance to methotrexate. It may be
`used as monotherapy or in combination with methotrexate or other nonbiologic disease-
`modifying antirheumatic drugs (DMARDs). The recommended dose of XELJANZ is 5 mg twice
`daily.
`
`The safety and efficacy of XELJANZ® for conditions other than RA have not yet been
`established.
`
`Limitations of Use
`XELJANZ should not be used in combination with biologic DMARDs or potent
`immunosuppressants such as azathioprine and cyclosporine.
`
`Serious Risks of XELJANZ® (tofacitinib)
`Serious Infections: Patients treated with XELJANZ are at increased risk for developing serious
`infections leading to hospitalization or death, including active tuberculosis (TB), invasive fungal
`infections, bacterial, viral and other infections due to opportunistic pathogens. XELJANZ should
`not be initiated in patients with an active infection, including localized infections. If a serious
`infection develops, XELJANZ should be interrupted until the infection is controlled.
`
`Malignancies and Lymphoproliferative Disorder: Consider the risks and benefits of
`XELJANZ treatment prior to initiating therapy in patients with a known malignancy other than a
`successfully treated non-melanoma skin cancer (NMSC) or when considering continuing
`XELJANZ in patients who develop a malignancy. Lymphoma and other malignancies have been
`reported in patients treated with XELJANZ.
`
`Laboratory Abnormalities: Lymphocytes, neutrophils, hemoglobin, and lipids should be
`monitored, as abnormalities in these parameters were associated with XELJANZ treatment in
`Phase 3 clinical trials. Please see the full Prescribing Information for more information.
`
`Reporting Adverse Events
`To report any adverse events with the use of XELJANZ, contact:
`• Pfizer Safety at 1-800-438-1985
`• MedWatch (FDA safety information and adverse event reporting program) at 1-800-332-1088
`or online at www.fda.gov/medwatch/report.htm
`
`This is not a comprehensive representation of the potential risks associated with use of
`XELJANZ. For a complete description of these potential risks, please visit the XELJANZ REMS
`web site (www.XELJANZREMS.com) for Full Prescribing Information and Medication Guide.
`
`
`
`Reference ID: 3213422
`
`15
`
`

`

`
`
`Appendix H: Screenshot of the Proposed REMS Website
`
`
`
`
`
`Reference ID: 3213422
`
`16
`
`

`

`
`
`_ {
`
`%
`
`I
`I E LJAH Z. 1.3
`[wlaotm bout-ole]
`
`Pruaibinp
`Infonn-Ition
`
`Risk Evaluation and Mitigation Strata gy {REMS}
`
`A Risk Eval ua‘tio n and hu'litiga‘tio n 5t ratfi [REI'LI'lSl is a st ratng to man—me lcnown o r
`pote ntial se rious risks flucia‘ted with a d rug p rod uct and is required by t he Food and
`DrugAdministrationto ensuretha‘tthe benefits ofthe dmgoutweighits risks.
`
`The goal ofthe KELIANZ RElu'lSis:
`
`I
`
`To info rm healt hcare p roviders and patients aho Lrt t he se rious risks associated with
`IELIANZtreatment.
`
`In orderfor Ffiaertocommu nicatecertain rislcsahout IELIANZ, Ffiaer has
`wo rlted wit h t he FDA to de'ue lo p a detailed co mm unicatio n plan to co mm u nicate t he
`followingimportant risks:
`
`seriousand otherimportant infections
`on
`on malignancia and other lyrmphopro fiferati'u'ediso rders
`o
`c hanges i n |al:|o rator'yr paramete rs, suc h as decreases i n lym p hoof-ta, neut ro p hi ls;
`and hemoglobin levels,and increasesin lipids.
`
`To learn more ahoutserio us risks read the prescrihirginformationand medication guide
`and disc ussit with your patients.
`
`Elementsofthe communication plan includethefollowing:
`
`I
`
`I
`
`I
`
`A Dear Healt hcare Fro-Hider Letter
`
`A Dear Pharmacist Letter
`
`Disse mi nation ofi nfo rma‘tio n al:|o ut t he lcnown and potential se rious risks
`alciated with IELIANZthro Lgh certain professional societifi' scientific meetirgs
`and jo u rnals
`
`I
`
`
`Disse mi nation ofi nfo rma‘tio n al:|o ut t he lcnown and potential se rious risks
`alciated wit h IELIANZ t hro Lgh t he it ELIANZ REI'LI'IS we l:|site
`Reference ID: 3213422
`Eontinue tocheclc hackon this wel:site;it will be updated toinclude additional information
`intended to assist inthe properoommunication ofthe rislcsofllt ELIANZ.
`
`
`
`('Jlmml-‘flimtiufl to
`_ _HCI-' [turmoil
`titlrntlfic Journals
`
`Hgifige
`Letter
`
`F'l‘m ”racist
`
`
`
`17
`
`

`

`
`
`
`
`Appendix I: Medication Guide
`
`MEDICATION GUIDE
`
`XELJANZ (ZEL’ JANS’)
` (tofacitinib)
`
`Read this Medication Guide before you start taking XELJANZ and each time you get
`a refill. There may be new information. This Medication Guide does not take the
`place of talking to your healthcare provider about your medical condition or
`treatment.
`What is the most important information I should know about XELJANZ?
`XELJANZ may cause serious side effects including:
`
`1. Serious infections.
`
`XELJANZ is a medicine that affects your immune system. XELJANZ can lower the
`ability of your immune system to fight infections. Some people have serious
`infections while taking XELJANZ, including tuberculosis (TB), and infections caused
`by bacteria, fungi, or viruses that can spread throughout the body. Some people
`have died from these infections.
` Your healthcare provider should test you for TB before starting XELJANZ.
` Your healthcare provider should monitor you closely for signs and symptoms of
`TB infection during treatment with XELJANZ.
`
`
`You should not start taking XELJANZ if you have any kind of infection unless your
`healthcare provider tells you it is okay.
`
`Before starting XELJANZ, tell your healthcare provider if you:
`
`think you have an infection or have symptoms of an infection such as:
`
`o fever, sweating, or chills
`o warm, red, or painful skin
`o muscle aches
`or sores on your body
`o cough
`o diarrhea or stomach pain
`o shortness of breath
`o burning when you urinate
`o blood in phlegm
`or urinating more often
`o weight loss
`than normal
`o feeling very tired
`
` are being treated for an infection
` get a lot of infections or have infections that keep coming back
` have diabetes, HIV, or a weak immune system. People with these conditions
`have a higher chance for infections.
` have TB, or have been in close contact with someone with TB
`
`live or have lived, or have traveled to certain parts of the country (such as the
`Ohio and Mississippi River val