February 2015 IMPORTANT DRUG WARNING Subject: Fatal and Serious Risk with the Use of Tecfidera® (dimethyl fumarate) delayed release capsules:  •  Progressive multifocal leukoencephalopathy (PML)  Dear Health Care Provider:  The purpose of this letter is to inform you of new important safety information for Tecfidera, approved for the treatment of patients with relapsing forms of multiple sclerosis. The information below reflects the PML case reported in October 2014 and the subsequent enclosed revised prescribing information dated December 2014.  Fatal and Serious Risks With Use of Tecfidera  Risk of progressive multifocal leukoencephalopathy (PML):  A fatal case of progressive multifocal leukoencephalopathy (PML) occurred in a patient with MS who received TECFIDERA for 4 years while enrolled in a clinical trial. The patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5x109/L for 3.5 years) while taking Tecfidera. The role of lymphopenia in this case is unknown. The patient had no other identified systemic medical conditions resulting in compromised immune system function and had not previously been treated with natalizumab, which has a known association with PML. The patient was also not taking any immunosuppressive or immunomodulatory medications concomitantly.  Prescriber Action Counsel patients about the risks and benefits of Tecfidera, including: • The potential risk of PML. At the first sign or symptom suggestive of PML, withhold Tecfidera and perform an appropriate diagnostic evaluation. • Tell your patients to contact their doctor immediately to report any symptoms associated with PML which are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. Lymphocyte monitoring has been revised. Obtain a CBC including lymphocyte count before initiating TECFIDERA, after 6 months, and every 6 to 12 months thereafter.  Consider interruption of TECFIDERA if lymphocyte counts <0.5 x 109/L persist for more than six months. Given the potential for delay in lymphocyte recovery after discontinuation of TECFIDERA, consider following lymphocyte counts until lymphopenia is resolved. Withholding treatment should be considered in patients with serious infections until the infection(s) is resolved. Decisions about whether or not to restart TECFIDERA should be individualized based on clinical circumstances  Reporting Adverse Events  Health care providers and patients are encouraged to report suspected adverse events in patients taking Tecfidera to Biogen Idec at 1-800-456-2255 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.  You may also contact our medical information department at 1-800-456-2255 if you have any questions about the information contained in this letter or the safe and effective use of Tecfidera.  This letter is not intended as a complete description of the benefits and risks related to the use of Tecfidera. Please refer to the full prescribing and approved patient information for complete risk information available at http://www.tecfidera.com/pdfs/full-prescribing-information.pdf.  Sincerely,  http://image.mail.biogen-idec.com/lib/fe9b12727660057c76/m/1/20150210_signature.jpg Amit Rakhit, MD SVP, Head, Global Medical Organization.