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WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
See full prescribing information for complete boxed warning
• TYSABRI increases the risk of progressive multifocal
leukoencephalopathy (PML), an opportunistic viral infection of the brain
that usually leads to death or severe disability (5.1)
• Monitor patients, and withhold TYSABRI immediately at the first sign or
symptom suggestive of PML (4, 5.1)
• TYSABRI is available only through a special restricted distribution
program called the TOUCH® Prescribing Program and must be
administered only to patients enrolled in this program (5.1, 5.2)


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4,5.1,5.2

4 CONTRAINDICATIONS

• TYSABRI is contraindicated in patients who have or have had progressive multifocal
leukoencephalopathy (PML) [see Boxed Warning, Warnings and Precautions (5.1)].
• TYSABRI should not be administered to a patient who has had a hypersensitivity
reaction to TYSABRI. Observed reactions range from urticaria to anaphylaxis [see
Warnings and Precautions (5.3)].

5 WARNINGS AND PRECAUTIONS
5.1 Progressive Multifocal Leukoencephalopathy (PML)
5.2 Distribution Program for TYSABRI

5.1 Progressive Multifocal Leukoencephalopathy (PML)
Progressive multifocal leukoencephalopathy, an opportunistic infection caused by the JC
virus that typically only occurs in patients who are immunocompromised, developed in three patients
who received TYSABRI in clinical trials [see Boxed Warning]. Two cases of PML were observed
among 1869 patients with multiple sclerosis treated for a median of 120 weeks. The third case
occurred among 1043 patients with Crohn’s disease after the patient received eight doses. Both
multiple sclerosis patients were receiving concomitant immunomodulatory therapy and the Crohn’s
disease patient had been treated in the past with immunosuppressive therapy.
In the postmarketing setting, additional cases of PML have been reported in multiple
sclerosis patients who were receiving no concomitant immunomodulatory therapy. In patients
treated with TYSABRI, the risk of developing PML increases with longer treatment duration, and for
patients treated for 24 to 36 months is generally similar to the rates seen in clinical trials. There is
limited experience beyond 3 years of treatment. There are no known interventions that can reliably
prevent PML or adequately treat PML if it occurs. It is not known whether early detection of PML
and discontinuation of TYSABRI will mitigate the disease.
Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy or
who have systemic medical conditions resulting in significantly compromised immune system
function should not be treated with TYSABRI.
Because of the risk of PML, TYSABRI is available only under a special restricted
distribution program, the TOUCH® Prescribing Program.
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In multiple sclerosis patients, an MRI scan should be obtained prior to initiating therapy with
TYSABRI. This MRI may be helpful in differentiating subsequent multiple sclerosis symptoms
from PML.
In Crohn’s disease patients, a baseline brain MRI may also be helpful to distinguish preexistent
lesions from newly developed lesions, but brain lesions at baseline that could cause
diagnostic difficulty while on TYSABRI therapy are uncommon.
Healthcare professionals should monitor patients on TYSABRI for any new sign or
symptom suggestive of PML. Typical symptoms associated with PML 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. The progression of deficits usually leads to death or severe disability over
weeks or months. Withhold TYSABRI dosing immediately at the first sign or symptom
suggestive of PML.
For diagnosis of PML, an evaluation including a gadolinium-enhanced MRI scan of the
brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended.
There are no known interventions that can adequately treat PML if it occurs. Three sessions of
plasma exchange over 5 to 8 days were shown to accelerate TYSABRI clearance in a study of 12
patients with MS who did not have PML, although in the majority of patients alpha-4 integrin
receptor binding remained high. Adverse events which may occur during plasma exchange
include clearance of other medications and volume shifts, which have the potential to lead to
hypotension or pulmonary edema. Although plasma exchange has not been studied in
TYSABRI treated patients with PML, it has been used in such patients in the postmarketing
setting to remove TYSABRI more quickly from the circulation.
Immune reconstitution inflammatory syndrome (IRIS) has been reported in TYSABRI
treated patients who developed PML and subsequently discontinued TYSABRI. In almost all
cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It
presents as an unanticipated clinical decline in the patient’s condition after return of immune
function (and in some cases after apparent clinical improvement) and, in the case of PML, is
often followed by characteristic changes in the MRI. TYSABRI has not been associated with
IRIS in patients discontinuing treatment with TYSABRI for reasons unrelated to PML. In
TYSABRI treated patients with PML, IRIS has been reported within days to several weeks after
plasma exchange. Monitoring for development of IRIS and appropriate treatment of the
associated inflammation during recovery from PML should be undertaken.
5.2 Distribution Program for TYSABRI
TYSABRI is available only under a special restricted distribution program called the
TOUCH® Prescribing Program. Under the TOUCH® Prescribing Program, only prescribers,
infusion centers, and pharmacies associated with infusion centers registered with the program are
able to prescribe, distribute, or infuse the product. For prescribers and patients, the TOUCH®
Prescribing Program has two components: MS TOUCH® (for patients with multiple sclerosis)
and CD TOUCH® (for patients with Crohn's disease). TYSABRI must be administered only to
patients who are enrolled in and meet all the conditions of the MS or CD TOUCH® Prescribing
Program. Contact the TOUCH® Prescribing Program at 1-800-456-2255 [see Boxed Warning].
To enroll in the TOUCH® Prescribing Program, prescribers and patients are required to
understand the risks of treatment with TYSABRI, including PML and other opportunistic
6
infections. Prescribers are required to understand the information in the Prescribing Information
and to be able to:
• Educate patients on the benefits and risks of treatment with TYSABRI, ensure that the
patient receives the Medication Guide, instruct them to read it, and encourage them to ask
questions when considering TYSABRI. Patients may be educated by the enrolled
prescriber or a healthcare provider under that prescriber’s direction.
• Review the TOUCH® Prescriber/Patient Enrollment form for TYSABRI with the patient
and answer all questions.
• As part of the initial prescription process for TYSABRI, obtain the patient’s signature
and initials on the TOUCH® program enrollment form, sign it, place the original signed
form in the patient’s medical record, send a copy to Biogen Idec, and give a copy to the
patient.
• Report serious opportunistic and atypical infections with TYSABRI to Biogen Idec or
Elan at 1-800-456-2255 and to the Food and Drug Administration’s MedWatch Program
at 1-800-FDA-1088.
• Evaluate the patient three months after the first infusion, six months after the first
infusion, and every six months thereafter.
• Determine every six months whether patients should continue on treatment and if so
reauthorize treatment every six months.
• Submit to Biogen Idec the TYSABRI Patient Status Report and Reauthorization
Questionnaire six months after initiating treatment and every six months thereafter.