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TYSABRI (natalizumab) injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TYSABRI safely and effectively. See full prescribing information for TYSABRI.
TYSABRI (natalizumab) injection, for intravenous use
Initial U.S. Approval: 2004
WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
See full prescribing information for complete boxed warning
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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)
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Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI (5.1)
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Monitor patients, and withhold TYSABRI immediately at the first sign or symptom suggestive of PML (4, 5.1)
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Because of the risk of PML, TYSABRI is available only through a restricted distribution program called the TOUCH® Prescribing Program (5.1, 5.2)
RECENT MAJOR CHANGES
Warnings and Precautions (5.1) 05/2015
INDICATIONS AND USAGE
TYSABRI is an integrin receptor antagonist indicated for treatment of:
Multiple Sclerosis (MS)
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TYSABRI is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See important information regarding the risk of PML with TYSABRI. (1.1, 5.1)
Crohn's Disease (CD)
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TYSABRI is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate conventional CD therapies and inhibitors of TNF-α. (1.2)
Important Limitations:
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In CD, TYSABRI should not be used in combination with immunosuppressants or inhibitors of TNF-α. (1.2)
DOSAGE AND ADMINISTRATION
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300 mg infused intravenously over one hour, every four weeks. Do not give as an intravenous push or bolus (2.1, 2.2)
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TYSABRI solution must be administered within 8 hours of preparation (2.3)
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Observe patients during the infusion and for one hour after the infusion is complete (2.4)
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In CD, discontinue in patients that have not experienced therapeutic benefit by 12 weeks of induction therapy, and in patients that cannot discontinue chronic concomitant steroids within six months of starting therapy (2.2)
DOSAGE FORMS AND STRENGTHS
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Solution [300 mg per 15 mL vial] for dilution prior to infusion (3)
CONTRAINDICATIONS
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Patients who have or have had PML (4)
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Patients who have had a hypersensitivity reaction to TYSABRI (4, 5.3)
WARNINGS AND PRECAUTIONS
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Herpes encephalitis and meningitis: Life-threatening and fatal cases have occurred. Discontinue TYSABRI if this occurs and treat appropriately (5.3)
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Hepatotoxicity: Significant liver injury, including liver failure requiring transplant, has occurred. Discontinue TYSABRI in patients with evidence of liver injury (5.4)
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Hypersensitivity reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have occurred. Permanently discontinue TYSABRI if such a reaction occurs (5.5)
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Immunosuppression/Infections: TYSABRI may increase the risk for certain infections. Monitor patients for development of infections due to increased risk with use of TYSABRI (5.6)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥ 10%)
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MS - headache, fatigue, arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea NOS, and rash (6.1)
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CD - headache, upper respiratory tract infections, nausea, and fatigue (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Biogen Idec at 1-800-456-2255 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
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Pregnancy: Based on animal data, may cause fetal harm. (8.1)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 5/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1. INDICATIONS AND USAGE
1.1. Multiple Sclerosis (MS)
TYSABRI is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See important information regarding the risk of PML with TYSABRI [see Warnings and Precautions (5.1)].
1.2. Crohn's Disease (CD)
TYSABRI is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. TYSABRI should not be used in combination with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α [see Warnings and Precautions (5.1)].
2. DOSAGE AND ADMINISTRATION
2.1. Multiple Sclerosis (MS)
Only prescribers registered in the MS TOUCH® Prescribing Program may prescribe TYSABRI for multiple sclerosis [see Warnings and Precautions (5.2)]. The recommended dose of TYSABRI for multiple sclerosis is 300 mg intravenous infusion over one hour every four weeks.
2.2. Crohn's Disease (CD)
Only prescribers registered in the CD TOUCH® Prescribing Program may prescribe TYSABRI for Crohn's disease [see Warnings and Precautions (5.2)].
The recommended dose of TYSABRI for Crohn's disease is 300 mg intravenous infusion over one hour every four weeks. TYSABRI should not be used with concomitant immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or concomitant inhibitors of TNF-α. Aminosalicylates may be continued during treatment with TYSABRI.
If the patient with Crohn's disease has not experienced therapeutic benefit by 12 weeks of induction therapy, discontinue TYSABRI. For patients with Crohn's disease who start TYSABRI while on chronic oral corticosteroids, commence steroid tapering as soon as a therapeutic benefit of TYSABRI has occurred; if the patient with Crohn's disease cannot be tapered off of oral corticosteroids within six months of starting TYSABRI, discontinue TYSABRI. Other than the initial six-month taper, prescribers should consider discontinuing TYSABRI for patients who require additional steroid use that exceeds three months in a calendar year to control their Crohn's disease.
2.3. Dilution Instructions
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Use aseptic technique when preparing TYSABRI solution for intravenous infusion. Each vial is intended for single use only.
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TYSABRI is a colorless, clear to slightly opalescent concentrate. Inspect the TYSABRI vial for particulate material and discoloration prior to dilution and administration. If visible particulates are observed and/or the liquid in the vial is discolored, the vial must not be used.
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To prepare the solution, withdraw 15 mL of TYSABRI concentrate from the vial using a sterile needle and syringe. Inject the concentrate into 100 mL of 0.9% Sodium Chloride Injection, USP. No other IV diluents may be used to prepare the TYSABRI solution.
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Gently invert the TYSABRI solution to mix completely. Do not shake. Inspect the solution visually for particulate material prior to administration.
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The final dosage solution has a concentration of 2.6 mg/mL.
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Following dilution, infuse TYSABRI solution immediately, or refrigerate solution at 2°C to 8°C, and use within 8 hours. If stored at 2°C to 8°C, allow the solution to warm to room temperature prior to infusion. DO NOT FREEZE.
2.4. Administration Instructions
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Infuse TYSABRI 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP, over approximately one hour (infusion rate approximately 5 mg per minute). Do not administer TYSABRI as an intravenous push or bolus injection. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP.
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Observe patients during the infusion and for one hour after the infusion is complete. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.5)].
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Use of filtration devices during administration has not been eva luated. Other medications should not be injected into infusion set side ports or mixed with TYSABRI.
3. DOSAGE FORMS AND STRENGTHS
TYSABRI is a concentrated solution that must be diluted prior to intravenous infusion. TYSABRI injection is supplied as 300 mg natalizumab in 15 mL (20 mg/mL) in a sterile, single-use vial free of preservatives.
4. CONTRAINDICATIONS
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TYSABRI is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [see Warnings and Precautions (5.1)].
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TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI. Observed reactions range from urticaria to anaphylaxis [see Warnings and Precautions (5.5)].
5. WARNINGS AND PRECAUTIONS
5.1. Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability, has occurred in patients who have received TYSABRI.
Three factors that are known to increase the risk of PML in TYSABRI-treated patients have been identified:
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Longer treatment duration, especially beyond 2 years. There is limited experience in patients who have received more than 6 years of TYSABRI treatment.
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Prior treatment with an immunosuppressant (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil).
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The presence of anti-JCV antibodies. Patients who are anti-JCV antibody positive have a higher risk for developing PML.
These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI.
Infection by the JC virus is required for the development of PML. Anti-JCV antibody testing should not be used to diagnose PML. Anti-JCV antibody negative status indicates that exposure to the JC virus has not been detected. Patients who are a |
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