TYSABRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYSABRI (TYSABRI).
Natalizumab is a recombinant humanized monoclonal antibody that binds to α4β1 and α4β7 integrins, blocking their interaction with vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MadCAM-1), thereby preventing lymphocyte migration across the blood-brain barrier and into inflamed parenchyma.
| Metabolism | Natalizumab is a monoclonal antibody; it is primarily catabolized by proteolytic degradation into small peptides and amino acids. No specific metabolic enzymes are involved; clearance occurs via reticuloendothelial system. |
| Excretion | Primarily via reticuloendothelial system catabolism; renal elimination accounts for <1%, biliary/fecal <1% as intact drug. |
| Half-life | Terminal half-life approximately 11 days (range 6–28 days); supports monthly IV dosing. |
| Protein binding | ~90% bound, primarily to albumin. |
| Volume of Distribution | 5.7 L (not weight-adjusted, ~0.08 L/kg for 70 kg human); reflects limited extravascular distribution consistent with a large monoclonal antibody. |
| Bioavailability | IV: 100% by definition; not administered via other routes. |
| Onset of Action | IV administration: Clinical effect on MRI lesions seen as early as 4 weeks; maximal pharmacodynamic effect (α4-integrin saturation) achieved within 24 hours. |
| Duration of Action | Pharmacodynamic effect (α4-integrin blockade) persists for ≥4 weeks post-dose; clinical durability supports monthly dosing; rebound disease activity may occur after discontinuation. |
| Molecular Weight | 149000 |
| Action Class | Alpha-4 integrin inhibitor |
300 mg intravenously infused over 1 hour every 4 weeks.
| Dosage form | VIAL |
| Renal impairment | No dose adjustment required for renal impairment. Not studied in severe renal impairment. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment. Not studied in severe hepatic impairment. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment, but caution due to potential increased immunosuppression. |
| 1st trimester | Natalizumab crosses the placenta. Limited human data; animal studies show no teratogenicity at clinical doses but increased fetal loss at high doses. Use only if clearly needed. |
| 2nd trimester | Continues to cross placenta. Monitor for potential immunosuppression in neonate. Use only if benefit outweighs risk. |
| 3rd trimester | Crosses placenta; may cause hematologic abnormalities (e.g., thrombocytopenia, anemia) in newborn. Use near term with caution; avoid if possible within 6 weeks of delivery. |
Clinical note
Comprehensive clinical and safety monograph for TYSABRI (TYSABRI).
| Placental transfer | Yes, IgG antibody; actively transferred across placenta, especially in second and third trimesters. |
| Breastfeeding | Natalizumab is excreted in human milk; levels are low relative to maternal dose. Potential for immunosuppression in infant; consider risk-benefit. Monitor infant for infections and bleeding. |
■ FDA Black Box Warning
Progressive multifocal leukoencephalopathy (PML) can occur with TYSABRI, usually in patients with longer treatment duration, prior immunosuppressant use, or presence of anti-JCV antibodies; PML is an opportunistic viral infection of the brain that usually leads to death or severe disability. Because of the risk of PML, TYSABRI is available only through a restricted distribution program called the TOUCH Prescribing Program.
| Serious Effects |
Progressive multifocal leukoencephalopathy (PML) or history of PMLHypersensitivity to natalizumab or any component
| Precautions | Progressive multifocal leukoencephalopathy (PML), Herpes infections (e.g., encephalitis, meningitis), Hypersensitivity reactions (including anaphylaxis), Hepatotoxicity (including liver failure), Immunosuppression/infections, Immunogenicity (development of anti-natalizumab antibodies) |
| Food/Dietary | No significant food interactions. TYSABRI is administered intravenously; no dietary restrictions required. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | TYSABRI (natalizumab) is an IgG4 monoclonal antibody. As such, it does not cross the placenta in significant amounts during the first trimester, but crosses increasingly during the second and third trimesters. There are no adequate and well-controlled studies in pregnant women. In animal studies, no teratogenic effects were observed at doses up to 30 mg/kg intravenously. However, there is a theoretical risk of fetal immune system effects due to blockade of α4-integrin. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
| Fetal Monitoring | Maternal monitoring: complete blood count (CBC), liver function tests (LFTs), and signs of progressive multifocal leukoencephalopathy (PML). Fetal monitoring: standard prenatal care including ultrasound to assess fetal growth and development. No specific additional fetal monitoring is recommended, but consider monitoring for potential effects on fetal immune system. |
| Fertility Effects | No specific studies on fertility effects in humans are available. In animal studies, natalizumab did not impair fertility in male or female rats at doses up to 30 mg/kg intravenously. However, due to its mechanism of action (α4-integrin blockade), there is a theoretical potential for effects on reproductive tissues, though no clear evidence of harm. |
| Clinical Pearls | TYSABRI (natalizumab) is a monoclonal antibody against alpha-4 integrin, used for relapsing-remitting multiple sclerosis (RRMS) and Crohn's disease. Risk of progressive multifocal leukoencephalopathy (PML) increases with JC virus antibody positivity, prior immunosuppressant use, and treatment duration >2 years. Administer as IV infusion over 1 hour; monitor for infusion reactions. Do not use with other immunosuppressants. Obtain baseline MRI and JC virus serology. |
| Patient Advice | TYSABRI increases the risk of a serious brain infection called PML, which can be fatal. You will be monitored regularly with blood tests and MRI. · Report any new or worsening neurological symptoms such as vision changes, confusion, weakness, or difficulty speaking immediately. · You must be tested for the JC virus before starting and periodically during treatment. · Do not take other immunosuppressive medications while on TYSABRI unless advised by your doctor. · Infusion reactions can occur; tell your nurse right away if you feel dizzy, short of breath, or have chest pain during the infusion. |