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boxed warning
WARNING: POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER, OTHER MALIGNANCIES, AND SERIOUS INFECTIONS Increased risk for developing post-transplant lymphoproliferative disorder (PTLD), predominantly involving the central nervous system (CNS). Recipients without immunity to Epstein-Barr virus (EBV) are at a particularly increased risk; therefore, use in EBV seropositive patients only. Do not use NULOJIX in transplant recipients who are EBV seronegative or with unknown EBV serostatus [see Contraindications (4) and Warnings and Precautions (5.1) ] . Only physicians experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe NULOJIX. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [see Warnings and Precautions (5.2) ] . Increased susceptibility to infection and the possible development of malignancies may result from immunosuppression [see Warnings and Precautions (5.1 , 5.3 , 5.4 , 5.5) ] . Use in liver transplant patients is not recommended due to an increased risk of graft loss and death [see Warnings and Precautions (5.6) ] . WARNING: POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER, OTHER MALIGNANCIES, AND SERIOUS INFECTIONS See full prescribing information for complete boxed warning. • Increased risk for developing post-transplant lymphoproliferative disorder (PTLD), predominantly involving the central nervous system (CNS). Recipients without immunity to Epstein-Barr virus (EBV) are at a particularly increased risk; therefore, use in EBV seropositive patients only. Do not use NULOJIX in transplant recipients who are EBV seronegative or with unknown serostatus. (4 , 5.1) • Only physicians experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe NULOJIX. (5.2) • Increased susceptibility to infection and the possible development of malignancies may result from immunosuppression. (5.1 , 5.3 , 5.4 , 5.5) • Use in liver transplant patients is not recommended due to an increased risk of graft loss and death. (5.6)
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warnings and cautions
5 WARNINGS AND PRECAUTIONS • Post-Transplant Lymphoproliferative Disorder (PTLD) : increased risk, predominantly involving the CNS; monitor for new or worsening neurological, cognitive, or behavioral signs and symptoms. (Boxed Warning , 4 , 5.1 , 5.6) • Other malignancies : increased risk with all immunosuppressants; appears related to intensity and duration of use. Avoid prolonged exposure to UV light and sunlight. (5.3) • Progressive Multifocal Leukoencephalopathy (PML) : increased risk; consider in the diagnosis of patients reporting new or worsening neurological, cognitive, or behavioral signs and symptoms. Recommended doses of immunosuppressants should not be exceeded. (5.4) • Other serious infections : increased risk of bacterial, viral, fungal, and protozoal infections, including opportunistic infections and tuberculosis. Some infections were fatal. Polyoma virus-associated nephropathy can lead to kidney graft loss; consider reduction in immunosuppression. Evaluate for tuberculosis and initiate treatment for latent infection prior to NULOJIX use. Cytomegalovirus and pneumocystis prophylaxis are recommended after transplantation. (5.1 , 5.4 , 5.5) • Liver transplant : use is not recommended. (5.6) • Acute Rejection and Graft Loss with Corticosteroid Minimization : corticosteroid utilization should be consistent with the NULOJIX clinical trial experience. (2.1 , 5.7 , 14.1) • Immunizations : avoid use of live vaccines during treatment. (5.8) • Coadministration with Anti-Thymocyte Globulin: in de novo kidney transplant recipients, especially those with other predisposing risk factors for venous thrombosis of the renal allograft, coadministration (at the same or nearly the same time) with anti-thymocyte globulin may pose a risk for venous thrombosis of the renal allograft. ( 5.9 , 6.2 , 7.3 ) • Risk of Rejection with Conversion From a CNI Based Maintenance Regimen: conversion of maintenance kidney transplant recipients from a CNI based to NULOJIX based maintenance regimen increases the risk of acute rejection. Conversion of stable kidney transplant recipients from a CNI based maintenance therapy to a belatacept based maintenance therapy is not recommended unless the patient is CNI intolerant. (5.10) 5.1 Post-Transplant Lymphoproliferative Disorder NULOJIX-treated patients have an increased risk for developing post-transplant lymphoproliferative disorde...
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adverse reactions
6 ADVERSE REACTIONS The most serious adverse reactions reported with NULOJIX are: • PTLD, predominantly CNS PTLD, and other malignancies [see Boxed Warning and Warnings and Precautions (5.1 , 5.3) ] • Serious infections, including JC virus-associated PML and polyoma virus nephropathy [see Warnings and Precautions (5.4 , 5.5 , 5.6) ] Most common adverse reactions (≥20% on NULOJIX treatment) are anemia, diarrhea, urinary tract infection, peripheral edema, constipation, hypertension, pyrexia, graft dysfunction, cough, nausea, vomiting, headache, hypokalemia, hyperkalemia, and leukopenia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. The data described below primarily derive from two randomized, active-controlled three-year trials of NULOJIX in de novo kidney transplant patients. In Study 1 and Study 2, NULOJIX was studied at the recommended dose and frequency [see Dosage and Administration (2.1) ] in a total of 401 patients compared to a cyclosporine control regimen in a total of 405 patients. These two trials also included a total of 403 patients treated with a NULOJIX regimen of higher cumulative dose and more frequent dosing than recommended [see Clinical Studies (14.1) ] . All patients also received basiliximab induction, mycophenolate mofetil, and corticosteroids. Patients were treated and followed for three years. CNS PTLD, PML, and other CNS infections were more frequently observed in association with a NULOJIX regimen of higher cumulative dose and more frequent dosing compared to the recommended regimen; therefore, administration of higher than the recommended doses and/or more frequent dosing of NULOJIX is not recommended [see Dosage and Administration (2.1) , Clinical Studies (14.2) ] . The average age of patients in Studies 1 and 2 in the NULOJIX recommended dose and cyclosporine control regimens was 49 years, ranging from 18 to 79 years. Approximately 70% of patients were male; 67% were white, 11% were black, and 22% other races. About 25% of patients were from the United States and 75% from other count...
adverse reactions table
Table 2: Summary of PTLD Reported in Studies 1, 2, and 3 Through Three Years of Treatment NULOJIX Nonrecommended Regimena (N=477)NULOJIX Recommended Regimenb (N=472)Cyclosporine (N=476)TrialEBV Positive (n=406)EBV Negative (n=43)EBV Unknown (n=28)EBV Positive (n=404)EBV Negative (n=48)EBV Unknown (n=20)EBV Positive (n=399)EBV Negative (n=57)EBV Unknown (n=20)a Regimen with higher cumulative dose and more frequent dosing than the recommended NULOJIX regimen. b In Studies 1 and 2 the NULOJIX regimen is identical to the recommended regimen, but is slightly different in Study 3.Study 1CNS PTLD11 Non-CNS PTLD 1 2 1 Study 2CNS PTLD11 11 Non-CNS PTLD 1 Study 3CNS PTLD 2 Non-CNS PTLD 1 Total (%)2 (0.5)5 (11.6)1 (3.6)3 (0.7)2 (4.1)001 (1.8)0