Natalizumab

What it is and how it works

Mechanism of Action Natalizumab products bind 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. Disruption of these molecular interactions prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue.

Mechanism class: Integrin Receptor Antagonists

Indications

is an integrin receptor antagonist indicated for treatment of: Multiple Sclerosis (MS) TYRUKO 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. Natalizumab products increase the risk of PML . When initiating and continuing treatment with TYRUKO, physicians should consider whether the expected benefit of TYRUKO is sufficient to offset this risk. Crohn's Disease (CD) • TYRUKO 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. Important Limitations: • In CD, TYRUKO should not be used in combination with immunosuppressants or inhibitors of TNF-α.

Dosage and administration (summary)

• 300 mg infused intravenously over one hour, every four weeks. Do not give as an intravenous push or bolus. ( 2.1 , 2.2 ) • TYRUKO solution must be administered within 4 hours of preparation. • 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.

Contraindications

• TYRUKO is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) . • TYRUKO is contraindicated in patients who have had a hypersensitivity reaction to natalizumab products or any of the ingredients in TYRUKO. Observed reactions range from urticaria to anaphylaxis . • Patients who have or have had PML • Patients who have had a hypersensitivity reaction to natalizumab products ( 4 , 5.3 )

Warnings and precautions

• 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 TYRUKO if these infections occur and treat appropriately. • Hepatotoxicity: Significant liver injury, including liver failure requiring transplant, has occurred. Discontinue TYRUKO in patients with evidence of liver injury. • Hypersensitivity reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have occurred. Permanently discontinue TYRUKO if such a reaction occurs.

Pregnancy

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 natalizumab products in pregnant women. Adverse fetal outcomes of neonatal thrombocytopenia and anemia have been reported (see Clinical Considerations ) .

Storage and supply

(natalizumab-sztn) injection, a sterile, preservative-free, colorless and clear to slightly opalescent solution for dilution prior to intravenous infusion, is supplied as one 300 mg/15 mL (20 mg/mL) single-dose vial per carton (NDC 61314-543-94). TYRUKO is available only through registered infusion centers participating in the TYRUKO REMS Program.

Source: Natalizumab-Sztn (Tyruko) — US FDA prescribing information, 2025-10-31, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.