Tysabri: Uses, Dosage & Side Effects

What Is Tysabri and What Is It Used For?

Tysabri contains the active substance natalizumab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody produced using recombinant DNA technology. As a monoclonal antibody, Tysabri is a highly specialized protein designed to recognize and bind to one specific molecular target in the body. In the case of natalizumab, that target is the alpha-4 subunit of integrins—cell surface adhesion molecules found on the surface of most white blood cells (leukocytes), except neutrophils.

Multiple sclerosis is a chronic autoimmune disease in which the body's own immune system attacks the myelin sheath, the protective covering around nerve fibers in the central nervous system (CNS). This inflammatory process damages the myelin and underlying nerve fibers, disrupting the transmission of electrical signals between the brain, spinal cord, and the rest of the body. The resulting nerve damage produces the diverse array of symptoms associated with MS, including difficulty walking, numbness or tingling in the face, arms, or legs, vision problems, fatigue, impaired balance or dizziness, bladder and bowel dysfunction, cognitive difficulties, depression, pain, and muscle stiffness or spasms.

The symptoms of MS vary widely from person to person. When symptoms flare up, it is called a relapse (also known as an exacerbation or attack). During a relapse, symptoms may appear suddenly within a few hours or develop gradually over several days. They typically improve over time—a period known as remission. Over the long term, however, repeated relapses can lead to progressive accumulation of disability.

Natalizumab works by binding to the alpha-4 integrin subunit on the surface of lymphocytes and monocytes, specifically the alpha-4-beta-1 integrin (also called VLA-4, very late antigen-4) and the alpha-4-beta-7 integrin. Under normal circumstances, these integrins interact with their receptors on vascular endothelial cells—VCAM-1 (vascular cell adhesion molecule-1) for VLA-4—to facilitate the migration of immune cells across blood vessel walls and into tissues. In the context of MS, this process allows auto-reactive T lymphocytes and other inflammatory immune cells to cross the blood-brain barrier and enter the CNS, where they initiate and perpetuate the inflammatory damage that characterizes the disease.

By blocking the alpha-4 integrin, natalizumab prevents inflammatory leukocytes from adhering to and transmigrating across the blood-brain barrier endothelium into the CNS. This mechanism effectively reduces the number of inflammatory cells entering the brain and spinal cord, thereby suppressing the neuroinflammatory process and protecting against the nerve damage that causes MS symptoms and disability. The result is fewer relapses and a significant slowing of disease progression.

The clinical efficacy of Tysabri was demonstrated in two landmark phase III clinical trials:

• AFFIRM (Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis): This pivotal randomized, double-blind, placebo-controlled trial enrolled 942 patients with relapsing-remitting MS. Over 2 years, natalizumab reduced the annualized relapse rate by 68% compared with placebo (0.23 vs. 0.73 relapses per year). The risk of sustained disability progression was reduced by 42%. Furthermore, MRI outcomes showed an 83% reduction in the accumulation of new or enlarging T2-hyperintense lesions.
• SENTINEL (Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a): This trial enrolled 1,171 patients who were experiencing relapses despite treatment with interferon beta-1a. Adding natalizumab to interferon beta-1a reduced the relapse rate by 54% and the risk of sustained disability progression by 24% compared to interferon beta-1a alone over 2 years.

Tysabri was first approved by the U.S. Food and Drug Administration (FDA) in November 2004 and by the European Medicines Agency (EMA) in June 2006. It is now approved in more than 80 countries worldwide. Due to the risk of PML (discussed in detail below), Tysabri is typically used in patients with highly active relapsing MS who have had an inadequate response to, or cannot tolerate, at least one other disease-modifying therapy. In some regions, it may also be used as a first-line treatment in patients with rapidly evolving severe relapsing-remitting MS.

What Should You Know Before Taking Tysabri?

Contraindications

Tysabri must not be used in the following circumstances:

• Hypersensitivity: If you are allergic to natalizumab or any of the other ingredients in the formulation, including sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate heptahydrate, sodium chloride, polysorbate 80 (E 433), and water for injections.
• Progressive multifocal leukoencephalopathy (PML): If you have been diagnosed with PML, you must not receive Tysabri.
• Severe immunocompromise: If you have a serious problem with your immune system, whether due to an underlying condition such as HIV infection, or as a result of current or previous immunosuppressive treatment.
• Concurrent immunosuppressants: Tysabri must not be used alongside other medications that suppress the immune system, including certain other disease-modifying therapies for MS.
• Active malignancy: If you have cancer, except for basal cell carcinoma of the skin, Tysabri should not be used.

Progressive Multifocal Leukoencephalopathy (PML) Risk

PML is the most significant risk associated with Tysabri treatment. It is caused by reactivation of the JC virus (John Cunningham virus), a common polyomavirus that infects the majority of the population without causing symptoms. Under conditions of immunosuppression, however, the JC virus can reactivate and cause a destructive infection of the brain's white matter, leading to progressive neurological deterioration.

Three factors significantly increase the risk of developing PML during Tysabri treatment:

• JC virus antibody positivity: The presence of anti-JCV antibodies in the blood indicates prior exposure to the virus and is a prerequisite for PML. Patients who test negative for JCV antibodies have a very low risk and should be retested at regular intervals, as seroconversion can occur over time.
• Duration of treatment: The risk of PML increases with longer exposure to Tysabri, particularly after 2 years of continuous treatment. The risk continues to increase with each additional year of exposure.
• Prior immunosuppressant use: Patients who have previously been treated with immunosuppressive agents (such as mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate) before starting Tysabri have a higher risk of PML.

Before treatment is initiated, all patients undergo a blood test to determine their JCV antibody status. An MRI scan of the brain is also performed as a baseline and is repeated regularly during treatment to monitor for early signs of PML. Patients who are JCV antibody positive may have their antibody index level measured to further stratify risk. Higher index values are associated with greater PML risk.

Symptoms of PML can resemble those of an MS relapse and may include progressive weakness on one side of the body, vision disturbances, changes in thinking, memory, and orientation, confusion, personality changes, and speech difficulties. If you or your caregiver notice any of these symptoms, contact your neurologist immediately. Early detection through clinical vigilance and regular MRI monitoring is critical, as treatment outcomes for PML are significantly better when the condition is identified before significant brain damage has occurred.

If PML is suspected or confirmed, Tysabri treatment is stopped immediately. Some patients may develop immune reconstitution inflammatory syndrome (IRIS) as natalizumab is cleared from the body and the immune system re-enters the CNS. IRIS can paradoxically worsen the clinical picture in the short term but represents the immune system's attempt to fight the JC virus infection.

Other Infections

Beyond PML, Tysabri can increase susceptibility to other infections. Because natalizumab partially suppresses immune surveillance in the CNS, opportunistic infections of the brain and other organs can occasionally occur. Herpes simplex encephalitis and herpes simplex meningitis have been reported in patients receiving Tysabri, including rare fatalities. If you develop symptoms suggestive of a serious infection—such as unexplained fever, severe diarrhea, shortness of breath, prolonged dizziness, headache, weight loss, lethargy, visual disturbances, or eye pain—inform your doctor promptly.

Changes in Blood Platelets

Natalizumab can reduce the number of platelets (thrombocytes), which are essential for blood clotting. This condition, known as thrombocytopenia, can impair the blood's ability to clot properly. Seek medical attention if you experience unexplained bruising, red or purple spots on the skin (petechiae), bleeding from cuts that does not stop, persistent gum or nose bleeding, blood in urine or stool, or bleeding in the whites of the eyes.

Pregnancy and Breastfeeding

Tysabri should not be used during pregnancy unless the potential benefit to the mother clearly justifies the potential risk to the fetus. Natalizumab has been shown to cross the placenta in animal studies, and changes in blood counts (particularly thrombocytopenia and anemia) have been observed in newborns of mothers treated with natalizumab during pregnancy. If you discover you are pregnant while taking Tysabri, or if you are planning to become pregnant, discuss this with your doctor immediately so that the risks and benefits can be carefully evaluated.

Breastfeeding is not recommended during Tysabri treatment. Natalizumab has been detected in breast milk in animal studies, and potential effects on the breastfed infant are not fully characterized. Your doctor can help you weigh the benefits of breastfeeding against the risks of drug exposure and decide whether to discontinue breastfeeding or discontinue Tysabri.

Children and Adolescents

Tysabri is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of natalizumab have not been established in this age group. Pediatric MS requires specialized management, and healthcare providers should consider age-appropriate treatment alternatives.

Driving and Operating Machinery

Dizziness is a very common side effect of Tysabri. If you experience dizziness, do not drive a car, ride a bicycle, or operate machinery until the symptom has resolved. Discuss with your doctor if dizziness persists or significantly affects your daily activities.

How Does Tysabri Interact with Other Drugs?

Drug interactions with Tysabri are primarily related to its immunomodulatory mechanism of action. Because natalizumab reduces immune surveillance by preventing lymphocyte migration into the CNS, combining it with other immunosuppressive or immunomodulatory agents could lead to an unacceptable cumulative effect on immune function, significantly increasing the risk of serious infections, including PML.

Major Interactions (Contraindicated)

Interactions Requiring Caution

Unlike many small-molecule drugs, natalizumab is a monoclonal antibody and is not metabolized by cytochrome P450 (CYP) enzymes. Therefore, traditional pharmacokinetic drug-drug interactions (those involving CYP enzyme inhibition or induction) are not expected with Tysabri. No formal drug interaction studies have identified pharmacokinetic interactions between natalizumab and other medications commonly used in MS patients, such as analgesics, antidepressants, or antiepileptic drugs.

When switching to Tysabri from another disease-modifying therapy, a washout period is typically required to allow the effects of the previous medication to diminish. The length of this washout period varies depending on the specific prior therapy and its pharmacological properties. Your neurologist will determine the appropriate timing based on your previous treatment, duration of use, and current immune function assessments. Similarly, when switching from Tysabri to another therapy, careful consideration must be given to the prolonged pharmacodynamic effects of natalizumab, which can persist for up to 12 weeks after the last dose.

What Is the Correct Dosage of Tysabri?

Tysabri is prescribed by a neurologist experienced in the diagnosis and management of multiple sclerosis. The treatment regimen is the same for all adult patients, regardless of body weight, as clinical trials demonstrated consistent efficacy across the weight range studied.

Adults

Before starting treatment, your neurologist will perform blood tests to check for JC virus antibodies and other relevant laboratory markers. A baseline MRI of the brain will also be obtained. These tests are repeated at regular intervals during treatment to monitor for safety.

If your clinical condition permits, your doctor may discuss the option of receiving subcutaneous injections outside of a specialist healthcare setting, such as at home. Self-administration (or administration by a caregiver) is possible after proper training, provided you meet certain criteria established by your neurologist. During the first two home-administered doses, a healthcare professional will supervise the injection process.

Patients should be monitored during subcutaneous injections and for 1 hour afterward for signs of injection reactions, including hypersensitivity reactions. After the first six Tysabri doses (regardless of administration route), the observation period may be adjusted based on clinical judgment.

Children

Tysabri is not approved for use in patients under 18 years of age. The safety and efficacy in this population have not been established. No dose recommendation can be made for pediatric patients.

Elderly

No specific dosage adjustment is required for elderly patients. However, Tysabri has not been extensively studied in patients over 65 years of age, and the benefit-risk assessment should take into account the age-related increase in susceptibility to infections and the potential for comorbidities that might affect immune function.

Missed Dose

If you miss your scheduled Tysabri dose, contact your neurologist to arrange the infusion or injection as soon as possible. You can then resume your regular every-4-weeks schedule from that point. Consistent dosing is particularly important during the first months of treatment to build and maintain therapeutic drug levels.

For subcutaneous administration, each complete dose requires two syringes. If you have received only one of the two syringes, contact your healthcare provider immediately for guidance. Do not attempt to make up the missed injection without medical advice.

Overdose

There is limited clinical experience with overdose of Tysabri. In controlled clinical settings, doses up to 6 mg/kg have been administered without dose-limiting toxic effects. In the event of an overdose, the patient should be monitored for signs of adverse effects, and appropriate supportive treatment should be provided. No specific antidote for natalizumab overdose exists. Plasma exchange or immunoadsorption procedures can accelerate the removal of natalizumab from the body if clinically indicated.

Stopping Treatment

Do not stop Tysabri without discussing it with your neurologist. Regular dosing is essential, particularly during the early months of treatment. Patients who have received one or two doses of Tysabri and then had a treatment gap of 3 months or more are at increased risk of allergic reactions when treatment is restarted. Additionally, MS disease activity may return after stopping Tysabri (sometimes as a rebound effect with increased relapse frequency), so a transition plan to an alternative disease-modifying therapy should be discussed with your neurologist.

Treatment Effectiveness and Antibodies

In some patients, the body may develop persistent antibodies against natalizumab (anti-natalizumab antibodies), which can reduce the drug's effectiveness and increase the risk of infusion or injection reactions. Your doctor can test for these antibodies through a blood test. If persistent neutralizing antibodies are confirmed, your doctor will discontinue Tysabri and discuss alternative treatment options.

What Are the Side Effects of Tysabri?

Like all medicines, Tysabri can cause side effects, although not everyone experiences them. The risk-benefit profile of Tysabri should be regularly reassessed by your neurologist throughout treatment. Below is a comprehensive overview of side effects organized by frequency, based on clinical trial data and post-marketing surveillance.

Allergic Reactions

Allergic reactions to Tysabri may occur during the infusion or injection or shortly afterward. Symptoms can include itchy rash (urticaria), swelling of the face, lips, or tongue, difficulty breathing, chest pain or discomfort, and changes in blood pressure. During intravenous administration, your healthcare provider will monitor you during the infusion and for 1 hour after its completion. If you are self-administering the subcutaneous formulation and experience signs of an allergic reaction, stop the injection immediately and seek emergency medical care.

Patients who have had a treatment gap of 3 months or more are at increased risk of allergic reactions when restarting Tysabri. This is thought to be related to the development of anti-natalizumab antibodies during the treatment-free period.

Reporting Side Effects

Reporting suspected side effects after a medication has been authorized is essential for ongoing monitoring of the drug's benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national regulatory authority (e.g., the FDA in the United States via MedWatch, the MHRA in the United Kingdom via the Yellow Card Scheme, or the EMA in the European Union). Information on how to report is typically included in the patient information leaflet provided with the medication.

How Should You Store Tysabri?

Proper storage of Tysabri is essential to maintain the medication's effectiveness and safety. The pre-filled syringes should be stored in a refrigerator at a temperature between 2°C and 8°C (36°F to 46°F). The syringes must not be frozen at any time, as freezing can damage the protein structure of the monoclonal antibody and render the medication ineffective or unsafe.

Keep the syringes in their original outer carton to protect them from light, as natalizumab is sensitive to light exposure. When preparing for administration, the syringes may be removed from the refrigerator and allowed to reach room temperature (up to 30°C / 86°F) for a total of no more than 24 hours, including the time required to reach room temperature and the administration time. Do not use external heat sources such as hot water or microwave ovens to warm the syringes.

If the syringes have been out of the refrigerator for less than 24 hours, they may be returned to the refrigerator and used before the expiration date printed on the label and carton. Record the date and time when the package was removed from the refrigerator on the carton. If the syringes have been at room temperature for more than 24 hours, they must be discarded.

Before use, visually inspect each syringe. The solution should be colorless to slightly yellow, slightly opalescent to opalescent, and free from visible particles. Do not use the syringe if the solution appears discolored, cloudy, or contains visible particles, or if the syringe is damaged or cracked. Small air bubbles in the solution are normal and do not indicate a problem.

Keep all medications out of the sight and reach of children. Do not use Tysabri after the expiration date stated on the label and carton. The expiration date refers to the last day of that month.

What Does Tysabri Contain?

Tysabri solution for injection is a colorless to slightly yellow, slightly opalescent to opalescent liquid. Each carton contains two pre-filled syringes. Tysabri is available in packs of two or six pre-filled syringes; not all pack sizes may be marketed in every country.

Sodium content: This medicine contains less than 1 mmol (23 mg) of sodium per 300 mg dose, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.

Polysorbate 80 content: This medicine contains 0.4 mg polysorbate 80 per pre-filled syringe (0.8 mg per full dose). Polysorbates can cause allergic reactions in some individuals. Inform your doctor if you have a known allergy to polysorbate 80 before starting treatment.

Tysabri is manufactured by Biogen Netherlands B.V., headquartered in Badhoevedorp, Netherlands. A biosimilar version, marketed as Tyruko (natalizumab), has also been approved in certain markets. Both products contain the same active ingredient and are intended for the same therapeutic indications.

References

1. European Medicines Agency (EMA). Tysabri Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/en/medicines/human/EPAR/tysabri
2. U.S. Food and Drug Administration (FDA). Tysabri Prescribing Information. Revised 2024. Available at: accessdata.fda.gov
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6. Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Multiple Sclerosis Journal. 2018;24(2):96-120. doi:10.1177/1352458517751049
7. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-1880. doi:10.1056/NEJMoa1107829
8. Ho PR, Koendgen H, Campbell N, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol. 2017;16(11):925-933. doi:10.1016/S1474-4422(17)30282-X
9. World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.

Editorial Team