pharmacopeia
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/api/v1/drug/natalizumab

Boxed warning

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI [ see Warnings and Precautions ( 5.1 ) ]. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium-enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [ see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ) ]. Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH ® Prescribing Program [ see Warnings and Precautions ( 5.2 ) ].

Mechanism of action

Sourced from openFDA

Natalizumab binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s). The receptors for the α4 family of integrins include vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium, and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) present on vascular endothelial cells of the gastrointestinal tract.

Integrin Receptor

Indications

Sourced from openFDA
  • TYSABRI is an integrin receptor antagonist indicated for treatment of: Multiple Sclerosis (MS) TYSABRI is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. TYSABRI increases the risk of PML [See Warnings and Precautions ( 5.1 ) ].ICD-10: G35

Contraindications

Sourced from openFDA
  • TYSABRI is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [ see Warnings and Precautions ( 5.1 ) ]. TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI.contraindicated

Dosage & administration

Sourced from openFDA

300 mg infused intravenously over one hour, every four weeks. Do not give as an intravenous push or bolus ( 2.1 , 2.2 ) TYSABRI solution must be administered within 48 hours of preparation ( 2.3 ) Observe patients during all infusions. Post-infusion, for the first 12 infusions, observe patients for one hour after the infusion is complete. For patients who have received 12 infusions without evidence of a hypersensitivity reaction, observe patients post-infusion for the 13th and subsequent infusions according to clinical judgment. ( 2.4 ) 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 ) 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.

Warnings & precautions

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Herpes infections: Life-threatening and fatal cases have occurred with herpes encephalitis and meningitis infections. Blindness has occurred in patients developing acute retinal necrosis. Discontinue TYSABRI if these infections occur and treat appropriately ( 5.3 ) Hepatotoxicity: Significant liver injury, including liver failure requiring transplant, has occurred. Discontinue TYSABRI in patients with evidence of liver injury ( 5.4 ) Hypersensitivity reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have occurred. Permanently discontinue TYSABRI if such a reaction occurs ( 5.5 ) 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 ) Hematological Abnormalities: TYSABRI may cause thrombocytopenia. Monitor patients for bleeding abnormalities. Discontinue TYSABRI in patients with thrombocytopenia. Neonatal thrombocytopenia and anemia have also occurred. Obtain a complete blood count in neonates exposed to TYSABRI in utero. ( 5.8 ) 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: The presence of anti-JCV antibodies.

Adverse reactions

Sourced from openFDA

The following serious adverse reactions are described below and elsewhere in the labeling: Progressive Multifocal Leukoencephalopathy (PML) [see Warnings and Precautions ( 5.1 )] Herpes Infections [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] Hypersensitivity/Antibody Formation [see Warnings and Precautions ( 5.5 )] Immunosuppression/Infections [see Warnings and Precautions ( 5.6 )] Hematological Abnormalities [see Warnings and Precautions ( 5.8 )] Most common adverse reactions (incidence ≥ 10%): 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 ) CD - headache, upper respiratory tract infections, nausea, and fatigue ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-800-456-2255 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (incidence ≥ 10%) were headache and fatigue in both the multiple sclerosis (MS) and Crohn's disease (CD) studies.

Use in specific populations

Sourced from openFDA

Pregnancy: Can cause fetal harm. ( 5.8 , 8.1 ) 8.1 Pregnancy Risk Summary There are no adequate data on the risk of major birth defects, miscarriage, or other adverse maternal outcomes associated with the use of TYSABRI in pregnant women. Adverse fetal outcomes of neonatal thrombocytopenia and anemia have been reported (see Clinical Considerations ) . In animal studies, administration of natalizumab during pregnancy produced fetal immunologic and hematologic effects in monkeys at doses similar to the human dose and reduced offspring survival in guinea pigs at doses greater than the human dose. These doses were not maternally toxic but produced the expected pharmacological effects in maternal animals [ see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Fetal/Neonatal Adverse Reactions Cases of neonatal thrombocytopenia and anemia in infants born to women exposed to TYSABRI during pregnancy were reported in the post-marketing setting [see Warnings and Precautions ( 5.8 )] . Therefore, a CBC should be obtained in neonates who were exposed to TYSABRI in utero .

Pharmacokinetics

Sourced from openFDA
Metabolism
Multiple Sclerosis (MS) Patients: In patients with MS, following the repeat intravenous administration of a 300 mg dose of TYSABRI, the mean ± SD maximum observed serum concentration was 110 ± 52 mcg/mL. Mean average steady-state trough concentrations ranged from 23 mcg/mL to 29 mcg/mL.

Overdosage

Sourced from openFDA

Safety of doses higher than 300 mg has not been adequately evaluated. The maximum amount of TYSABRI that can be safely administered has not been determined.

Approval history

Sourced from openFDA
  • Nov 23, 2004BLABLA125104Biogen Idec
  • Aug 24, 2023BLABLA761322Sandoz Inc

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
180,200 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Fatigue19,54511%
  2. 2Multiple Sclerosis Relapse16,8589.4%
  3. 3Headache9,9725.5%
  4. 4Multiple Sclerosis9,7365.4%
  5. 5Gait Disturbance9,4955.3%
  6. 6Fall8,0324.5%
  7. 7Asthenia8,0044.4%
  8. 8Memory Impairment7,9454.4%
  9. 9Malaise7,3644.1%
  10. 10Drug Ineffective6,8983.8%
  11. 11Urinary Tract Infection6,2963.5%
  12. 12Pain5,9563.3%
  13. 13Balance Disorder5,6933.2%
  14. 14Hypoaesthesia5,4183.0%
  15. 15Pain In Extremity4,9262.7%

Literature

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Recent PubMed references pinned to Natalizumab as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 149 ClinicalTrials.gov registrations naming Natalizumab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Natalizumab work?
Natalizumab binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s). The receptors for the α4 family of integrins include vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium, and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) present on vascular endothelial cells of the gastrointestinal tract.
What is Natalizumab used for?
According to FDA labeling, Natalizumab carries indications including: TYSABRI is an integrin receptor antagonist indicated for treatment of: Multiple Sclerosis (MS) TYSABRI is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. TYSABRI increases the risk of PML [See Warnings and Precautions ( 5.1 ) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Natalizumab?
Natalizumab is classified as Monoclonal antibodies, Integrin Receptor Antagonist, Integrin Receptor Antagonists, Decreased Adhesion Factor Activity.
What are the brand names for Natalizumab?
Natalizumab is marketed under brand names including Tyruko, Tysabri.
What are the contraindications for Natalizumab?
Natalizumab labeling lists contraindications including: TYSABRI is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [ see Warnings and Precautions ( 5.1 ) ]. TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI.. Always consult the full prescribing information and a clinician.
Note. Data for natalizumab is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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