Section 04 · Monograph
Natalizumab
Reviewed Nov 2026FDA label
TysabriAnti-α4 integrin mAb
- Forms
- IV/SC: 300mg
- Dose
- 300mg every 4 weeks
- MOA
- Blocks lymphocyte migration across BBB
Black Box Warning
- Increases risk of progressive multifocal leukoencephalopathy (PML), a rare, often fatal opportunistic CNS infection caused by JC virus
- Risk factors for PML: anti-JCV antibody positivity, prior immunosuppressant use, longer treatment duration (especially >24 months)
- Available only through the restricted TOUCH Prescribing Program
Indications
- Relapsing forms of multiple sclerosis, to slow physical disability and reduce relapsesFDA-labeled
- Moderately to severely active Crohn's disease with inadequate response to conventional therapy and TNF inhibitorsFDA-labeled
Mechanism of Action
- Humanized monoclonal antibody against alpha-4 integrin
- Blocks alpha-4-mediated adhesion of leukocytes to vascular endothelium, reducing migration of inflammatory cells across the blood-brain barrier into CNS parenchyma
Full Dosing
Adult / usual
- 300 mg IV infusion over approximately 1 hour, every 4 weeks
Renal
- No dose adjustment established for renal or hepatic impairment
Contraindications
- History of PML
- Known hypersensitivity to natalizumab
Drug Interactions
- Avoid concurrent use with other immunosuppressants or immunomodulators (increases PML and infection risk)
- Avoid concomitant antineoplastic, immunosuppressant, or immunomodulatory agents
Adverse Effects
- Headache
- Fatigue
- Arthralgia
- Urinary tract infection
- Lower respiratory tract infection
- Gastroenteritis
- Vaginitis
- Depression
- Infusion-related reactions (dizziness, nausea, urticaria, rigors)
- Hepatotoxicity (rare)
- Hypersensitivity reactions including anaphylaxis
Monitoring Parameters
- Anti-JCV antibody status periodically
- MRI at baseline and periodically to monitor for PML
- Liver function tests
- Signs/symptoms of PML (progressive weakness, vision changes, cognitive/behavioral changes)
- Infusion reactions during and after administration
Pregnancy & Lactation
- Limited human data; consider pregnancy exposure registry
- May cause fetal hematologic abnormalities if used in third trimester
- Present in human milk; weigh benefits vs risks