• Tysabri is a brand (trade) name for natalizumab which may be used to treat multiple sclerosis (MS) or Crohn's disease.
• Tysabri (natalizumab) works by blocking the migration of lymphocytes (a type of immune cell) from the lymph nodes, across the epithelium, and into inflamed tissue. It binds to the α4-subunit of α4β1 and α4β7 integrins (a type of receptor) which is present on all leukocytes apart from neutrophils and prevents them from binding to their counter receptors. It may also act in several other ways to prevent the further recruitment and inflammatory activity of activated immune cells.
• The way Tysabri works specifically in MS or Crohn's disease is not completely understood. In MS it may be due to a reduction of lymphocyte migration into brain tissue and a reduction in plaque formation.
• In Crohn's disease, the interaction of α4β7 integrin with the endothelial receptor MAdCAM-1 has been implicated as a major contributor to inflammation that is a significant characteristic of Crohn's disease. MAdCAM-1 is mainly expressed in gut tissue and expression of MAdCAM-1 is increased at active sites of inflammation in people with Crohn's disease, and may significantly increase the recruitment of leukocytes to the mucosa. Tysabri blocks this interaction.
• Tysabri belongs to the class of medicines known as integrin receptor antagonists. It may also be called a selective immunosuppressant or a monoclonal antibody.

• May be used for the treatment of relapsing forms of MS in adults. This includes clinically isolating syndrome, relapsing-remitting disease, and active secondary progressive disease.
• May also be used in adults with moderately to severely active Crohn's disease (CD) who don't respond or are unable to tolerate conventional CD therapies and inhibitors of TNF-α. Do not use it in combination with other immunosuppressants such as 6-mercaptopurine, azathioprine, cyclosporine, methotrexate, or inhibitors of TNF-α.
• Reduces inflammation and subsequent damage.
• Given every 4 weeks by intravenous infusion over one hour. The usual dosage is 300mg.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Headache, fatigue, joint pain, infection, vaginitis, depression, pain, abdominal discomfort, diarrhea, nausea, and rash are the most common side effects reported. Irregular menstruation, vertigo, urinary urgency or frequency, or thrombocytopenia may also occur.
• Increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella-zoster viruses. May be life-threatening and sometimes fatal.
• Although rare, hypersensitivity reactions have occurred with Tysabri. Symptoms include a rash, fever, dizziness, itching, nausea, low blood pressure, and shortness of breath.
• A higher risk of acute retinal necrosis (ARN), a herpes viral infection of the retina has been observed in patients being administered Tysabri; some patients have been left with blindness in one or both eyes. Eye symptoms include decreased vision, redness, or eye pain.
• Serious liver injury including acute liver failure that has required a transplant, has been reported in patients treated with Tysabri. Monitor for signs of liver injury, including significantly increased liver enzymes and high total bilirubin. May occur as early as six days after the first dose or after multiple doses. Discontinue Tysabri with signs of liver injury or jaundice.
• Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients who have received Tysabri. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that often leads to death or severe disability. Posterior reversible encephalopathy syndrome (PRES) and respiratory effects have also been reported.
• May not be suitable for people who have medical conditions that can weaken their immune system such as HIV or AIDS, leukemia, or lymphoma, or an organ transplant.
• Because of the risk of PML, Tysabri is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH Prescribing Program, which has two components, one for MS and one for CD. Only prescribers registered in this program may prescribe Tysabri for MS or CD.
• Do not use Tysabri in people with a history of PML or a history of hypersensitivity to Tysabri.
• Tysabri may increase the risk of infections, such as pneumonia, urinary tract infections, vaginal infections, and herpes infections. The risk is greater if the person is also taking other drugs that suppress the immune system, such as chemotherapy agents, immune-modulating therapies, or other immunosuppressants.
• Tysabri must be administered by a health professional. The infusion takes an hour and the person should be observed for one hour after the infusion is complete. Tysabri infusion should be stopped immediately if the person experiences a hypersensitivity reaction.
• May cause changes in laboratory test results, such as increases in lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. These returned to baseline usually within 16 weeks of the last dose.
• No data are available on the effects of vaccination on people receiving Tysabri.
• There is the potential for immunogenicity with Tysabri and the development of antibodies. Approximately 9% of people developed detectable antibodies at least once during treatment and the presence of anti-natalizumab antibodies correlated with a reduction in Tysabri concentrations.
• There is no data regarding the use of Tysabri during pregnancy or while breastfeeding; however, Tysabri has been detected in breast milk. Weigh up the risks versus benefits before prescribing.
• The safety and effectiveness of Tysabri has not been established in children and adolescents under the age of 18.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• Tysabri is given once every 4 weeks by a registered infusion center or pharmacy that is enrolled in the Touch Prescribing program. To locate these infusion centers call Biogen at 1-800-456-2255. Keep your appointments as scheduled and ensure you make any up that you miss.
• Read the medication guide that your doctor gives you because it explains everything you need to know about Tysabri. You will need to sign a Patient Prescriber Enrollment Form before you start Tysabri.
• Report any persistent new or worsening symptoms to your prescriber.
• You are at an increased risk of infections, while you are being administered Tysabri because it lowers your immune response. The immune response to live vaccines may also be diminished and you should ensure your vaccination status is up to date before receiving Tysabri. See your doctor immediately if you develop any signs of an infection which may include fever, pain, swelling, redness, or a discharge.
• Tysabri increases your risk of developing certain herpes viral infections including encephalitis and meningitis which could be fatal and acute retinal necrosis that may cause blindness.
• See your doctor if you experience any unusual or worrying side effects, such as abdominal pain, fainting, heart palpitations, a rash, nausea, vomiting, dark urine, skin yellowing, shortness of breath, fever, or vision problems. Also, call your doctor if you experience any of the following symptoms while you are receiving Tysabri and for 6 months after stopping it: problems with your thinking, balance, eyesight, strength, using your arms or legs, or weakness on one side of your body.;
• Can also increase your risk of developing progressive multifocal leukoencephalopathy (PML) a serious viral infection, and symptoms may include progressive weakness on one side of the body, limb clumsiness, vision disturbance, and changes in thinking, memory, and orientation leading to confusion and personality changes. See your doctor immediately if any of these symptoms happen to you. The risk of developing PML is higher in people who have been infected by the John Cunningham Virus (JCV), who have received Tysabri for more than 2 years, or who have received certain medicines that weaken the immune system before starting Tysabri.
• Tysabri may lower your platelet count which may cause severe bleeding that could be life-threatening. Talk to your doctor if you experience easy bruising, prolonged bleeding from cuts, abnormally heavy periods, or bleeding from the nose or gums.
• It is unknown how Tysabri may affect an unborn baby or a newborn if you are breastfeeding. Talk to your doctor about the risk versus benefits of taking Tysabri during pregnancy or while breastfeeding.
• Tell all health professionals that you are receiving Tysabri. Tysabri may interact with several other medications, including supplements and herbals brought over the counter from a health store.

• If a patient with CD has not experienced a benefit after 12 weeks of Tysabri, then it should be discontinued. If Tysabri is started while a person is on oral corticosteroids, then these should be tapered off and discontinued as soon as a therapeutic benefit of Tysabri is recognized. If a person with CD cannot be tapered off oral corticosteroids within six months of starting Tysabri, then it should be discontinued.
• Tysabri provided a reduction in the risk of sustained disability in patients with MS by 42% compared with placebo after 2 years of treatment. The annualized relapse rate decreased by 67% in those treated with Tysabri compared to a placebo. No patients in the Tysabri group reported new or newly enlarging T2-hyperintense lesions compared with 5 in the placebo group (out of 315).
• A reduction in the outcome: "Increase in disability sustained" was reported at around week 14 with Tysabri which persisted and increased until week 120.
• Three RCTs investigated Tysabri for CD. Clinical response was seen by week 8 in 56% of Tysabri patients (40% of placebo patients), and by week 12 in 60% of Tysabri patients (44% of placebo patients). Clinical remission was reported in 32% of Tysabri patients at week 8 and 21% of placebo patients, and week 12 by 37% of Tysabri patients and 25% of placebo patients. Clinical response to Tysabri persisted through month 9 for 61% of patients receiving Tysabri and for 15 months for 54%, compared to 29% and 20% respectively for placebo patients. 45% of patients achieved clinical remission by month 9 and 40% by month 15.

Medicines that interact with Tysabri may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Tysabri. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Tysabri interacts with over 300 medications; the majority of these interactions are considered major or moderate. Common medications that may interact with Tysabri include:

• antineoplastics, such as capecitabine, or cyclophosphamide
• other biologics, such as adalimumab, etanercept, golimumab, or infliximab
• busulfan
• cannabidiol
• corticosteroids (such as budesonide, prednisone, or dexamethasone)
• fingolimod
• herbals, such as black cohosh or brewer's yeast
• hydroxyurea
• immunosuppressants such as azathioprine, cyclosporine, or tacrolimus
• interferon
• live vaccines and some other vaccines, such as BCG, cholera, sars-CoV-2 (covid-19) vaccines, measles, hepatitis b vaccines, yellow fever, or live influenza vaccines
• methotrexate
• probiotics, such as lactobacillus

Tysabri may have additive immune-suppressing effects when given with any other medications such as anticancer drugs, immune-modulating, or immunosuppressive therapies, which may increase a person's risk for infection.

Do not use it in combination with other immunosuppressants such as 6-mercaptopurine, azathioprine, cyclosporine, methotrexate, or inhibitors of TNF-α.

Note that this list is not all-inclusive and includes only common medications that may interact with Tysabri. You should refer to the prescribing information for Tysabri for a complete list of interactions.