July 8, 2011
FDA and Bristol-Myers Squibb are informing healthcare professionals about the risk of post-transplant lymphoproliferative disorder (PTLD) and progressive multifocal leukoencephalopathy (PML) associated with belatacept (Nulojix). A risk evaluation and mitigation strategy (REMS) was developed to ensure prescribers are aware of these serious and sometimes fatal adverse events so they may carefully weigh the benefits and risks before prescribing belatacept. Belatacept inhibits the activation of T-cells and is used in combination with corticosteroids and other immunosuppressive agents to prevent organ rejection in Epstein-Barr virus (EBV) positive kidney transplant patients. Post-transplant lymphoproliferative disorder associated with belatacept treatment usually involves the central nervous system. The risk for PTLD is increased in EBV negative patients. The approved labeling contains a boxed warning regarding the risk of PTLD. Do not administer belatacept in EBV negative patients or patients whose EBV status is unknown. Progressive multifocal leukoencephalopathy occurred in patients treated with higher than recommended doses of belatacept. Do not exceed the recommended belatacept dose.
The belatacept REMS program contains a Communication Plan to educate healthcare professionals about the risk of PTLD and PML. Healthcare providers are advised to read the labeling and other educational materials and discuss the potential risks with the patient. Monitor patients for new or worsening neurologic or behavioral changes. If symptoms are detected, consider reducing the belatacept dose or discontinuing therapy. In addition to the REMS program, BMS established the ENLiST Registry to continue to collect information and evaluate the safety of belatacept. The company encourages registry enrollment of all kidney transplant patients treated with belatacept.
Additional information is available at the following links:
- MedWatch Alert:
- Dear Healthcare Professional Letter:
- Healthcare Professional Fact Sheet:
- Medication Guide:
The FDA requires the distribution of Medication Guides for drugs determined to be a serious and significant public health concern. With the exception of the erythropoiesis-stimulating agents (ESAs; eg, darbepoetin alfa, epoetin alfa) and naltrexone suspension, this requirement applies primarily to medications dispensed in the outpatient setting (refer to Code of Federal Regulations 21CFR208.1) for patient self-administration. When other prescription medications are administered to patients by healthcare professionals (eg, in the hospital, in infusion centers, dialysis centers, clinics, or offices), distributing a Medication Guide is not required, although it may be appropriate to educate patients about the potential hazards of prescription medications, at the clinician’s discretion. When ESAs are administered to patients by healthcare professionals, a Medication Guide must be distributed when the patient starts therapy, at least once monthly during therapy, and whenever the Medication Guide is substantially updated. When naltrexone suspension (Vivitrol) is administered to patients by healthcare professionals, a Medication Guide must be distributed when the patient starts therapy and before each injection. The complete list of drugs that require a Medication Guide as part of the FDA-regulated product labeling is available online at: http://www.fda.gov/cder/Offices/ODS/labeling.htm. For more information about the special requirements for ESA Medication Guide, see http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm.
July 8, 2011; University of Utah, Drug Information Service. Copyright 2011, Drug Information Service, University of Utah, Salt Lake City, UT.