The information in this medication sheet has been adapted from the FDA-approved prescribing information for Tysabri.
Tysabri is a laboratory-produced monoclonal antibody. It is designed to hamper movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier” into the brain and spinal cord. Tysabri was evaluated in a pair of two-year, controlled clinical trials:
- Study I compared Tysabri to placebo in patients who had not received any interferon-beta or glatiramer acetate for at least the previous six months.
- Study II involved patients who had experienced one or more relapses while on treatment with Avonex®. Half of the group took Tysabri in addition to their Avonex; half of the group took Avonex plus a placebo.
In both studies, those taking the medication had a reduced risk of disability progression and experienced fewer exacerbations (relapses) compared with the group taking a placebo. Tysabri has not been studied in people with primary progressive MS or in children.
Approval by the U.S. Food and Drug Administration (FDA)
Tysabri was approved by the U.S. Food and Drug Administration (FDA) in 2006 as a monotherapy (not to be used in combination with another disease-modifying therapy) for the treatment of patients with relapsing forms of MS to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations. Because Tysabri increases the risk of progressive multifocal leukoencephalopathy (PML — see Warnings and Precautions), it is generally recommended for patients who have had an inadequate response to, or cannot tolerate, an alternate MS therapy.
In January, 2012, the FDA changed the labeling for Tysabri to indicate that testing positive for anti-JC virus (JCV) antibodies has been shown to be a risk factor for PML. A person’s antibody status can be determined with a blood test. The FDA also approved the Stratify JCV Antibody ELISA test; a positive result on this test means that a person has been exposed to JCV in the past. Only people who have been exposured to JCV appear to be at risk of PML. The risks and benefits of starting or continuing treatment with Tysabri should be considered carefully in any person who is anti-JCV antibody positive and has one or more of the other known risk factors for PML. The other known risk factors are:
- Longer time on treatment with Tysabri – especially over two years
- Prior treatment with an immunosuppressant medication (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil)
A person who tests positive for anti-JCV antibodies but has no other risk factors has a less than 1 in 1000 risk of developing PML. A person with all three risk factors has an 11 in 1000 risk of developing PML.
A person who tests negative for anti-JCV antibodies is still at risk of developing PML because she or he may become infected with the JCV at any time. Therefore, periodic re-testing for JCV antibodies is recommended.
On August 15, 2012, the FDA required another change to the prescribing information, recommending that patients with a negative anti-JCV antibody test result should be retested every 6 months.
- Tysabri is given once every four weeks by intravenous infusion.
Because of the risk of PML, Tysabri is available only through a special distribution program called the TOUCH™ Prescribing Program.
- Before starting treatment with Tysabri, you will learn about the TOUCH program and be asked to sign the Prescriber/Patient Enrollment Form.
- Only physicians, infusion centers, and pharmacies associated with the infusion centers that are registered with the TOUCH program can prescribe, distribute, or infuse the medication.
- An MRI scan should be obtained prior to initiating therapy with Tysabri because this MRI may help your physician differentiate multiple sclerosis symptoms that occur over time from symptoms caused by PML.
- Once you have started taking Tysabri, you should see your prescribing doctor three months after the first infusion, six months after the first infusion, and at least as frequently as every six months thereafter.
Before each infusion, you will be asked a series of questions by the doctor or nurse at the infusion center to confirm that Tysabri is still appropriate and safe for you. Tell the doctor or nurse at the infusion center:
- About all medications you are taking (prescription and non-prescription, including supplements)
- About any other medical conditions you have
- If you have experienced any new or worsening medical problems (such as changes in thinking, eyesight, balance, strength, etc.).
- If you have experienced any hives, itching, or trouble breathing during or after an infusion of Tysabri
- If you have a fever or infection (including long-lasting infections or shingles)
- If you are pregnant or plan to become pregnant
- If you are breastfeeding
Warnings and Precautions
The FDA prescribing information about Tysabri includes a black box warning about the risk of progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability.
- Although the cases of PML that occurred in the clinical trials occurred only in patients who were also taking another immunomodulating or immunosuppressing medication, additional cases of PML in people who were not taking another immunomodulating or immunosuppressing medication at the same time have been reported in the post-marketing phase.
- The typical symptoms associated with PML progress over days to weeks, and can include clumsiness and progressive weakness on one side of the body, disturbances of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. Changes of this kind should be reported immediately to one's physician.
- If the doctor suspects PML, the Tysabri will be stopped immediately and an evaluation will be done, including a gadolinium-enhanced MRI of the brain and possibly a cerebrospinal fluid analysis for the presence of JC viral DNA. If this initial evaluation for PML is negative, but the physician still suspects that it may be present, no further doses of Tysabri will be given and the tests will be repeated.
- There are no interventions that are known to cure PML once it occurs, but plasma exchange to remove Tysabri from the blood stream as quickly as possible may provide some benefit. Immune reconstitution inflammatory syndrome (IRIS) has been reported in some patients in the days or weeks following plasma exchange to treat PML. IRIS appears as an unanticipated worsening in the person's condition--caused by inflammation--as immune function returns following the plasma exchange. Anyone receiving plasma exchange to treat PML needs to be monitored for IRIS and treated if it occurs.
- Based on post-marketing experience with Tysabri, the FDA added an additional warning to the product’s labeling information in February, 2008. Tysabri has been found to increase the risk of liver damage, even after a single dose. Any person experiencing symptoms of liver injury, including yellowing of the skin and eyes (jaundice) unusual darkening of the urine, nausea, feeling tired or weak, and vomiting, should contact his or her physician immediately. Blood tests can be done to check for liver damage. Treatment with Tysabri should be discontinued in anyone with jaundice or laboratory findings that indicate significant liver injury.
- Tysabri can increase the risk for certain infections, including PML; it should not be used by any person who is taking medication(s) that can weaken the immune system, or anyone who has a medical condition that can weaken the immune system, such as HIV infection or AIDS, leukemia or lymphoma, an organ transplant, or others.
- Allergic reactions can occur — including serious ones. Symptoms of an allergic reaction can include: hives, itching, trouble breathing, chest pain, dizziness, chills, rash, nausea, flushing of skin, low blood pressure. Serious allergic reactions usually happen within 2 hours of the start of the infusion, but can happen any time after. Contact your physician promptly about any of these symptoms.
- Tysabri should not be used during pregnancy or by any woman who is trying to become pregnant. Women taking Tysabri should use birth control measures at all times. If you want to become pregnant while being treated with Tysabri, discuss the matter with your physician. If you become pregnant while using Tysabri, contact your physician.
- No data are yet available on the effects of vaccination in patients receiving Tysabri.
Possible Side Effects
- Side effects that may go away as your body adjusts to the medication and do not require medical attention unless they continue or are bothersome: headache, pain in your arms or legs*, feeling tired*, joint pain, depression*, diarrhea, pain in the stomach area.
- Because Tysabri affects your immune system, it can increase your chance of getting an unusal or serious infection, such as pneumonia, serious urinary tract infection, gastroenteritis, vaginal infection, tooth infection, and others. Contact your physican promptly about any problems of this kind.
*Some side effects of Tysabri may be confused with symptoms of MS. A person who abruptly experiences any of these changes should consult his or her health professional.
Tysabri is a registered trademark of Elan Pharmaceuticals, Inc.
Avonex is a registered trademark of Biogen Idec.
Betaseron is a registered trademark of Bayer Schering Pharma Aktiengesellschaft.
Rebif is a registered trademark of Ares Trading S.A.
TOUCH is a trademark of Biogen Idec and Elan Pharmaceuticals, Inc.