Tysabri (Natalizumab) MOA and Indications

Tysabri contains “Natalizumab” considered an evolution in the management of many autoimmune diseases.

It is manufactured by Biogen Company and got FDA approval in 2004. In 2005 the drug was voluntarily withdrawn from the U.S. market when cases of progressive multifocal leukoencephalopathy were reported. However, it was again approved by FDA in 2006 due to its benefits.

Tysabri (Natalizumab) Mechanism of action

• • It is a recombinant humanized monoclonal antibody that binds to the alpha-4 subunit of alpha4-beta1 and alpha4-beta7 integrins.
  • It prevents leucocyte endothelial adhesion and leucocyte extravasation.

• Peak plasma concentration:

  • 64-132mcg/mL

• Distribution:

  • Its volume of distribution is 5.7 L in Multiple sclerosis and 5.2 L in Crohn’s disease.

• Elimination:

  • Its half-life is 7-14 days when used in doses for MS and 3-7 days when used for Crohn’s disease

• Administration:

  • Intravenous administration
  • Dosage: 300mg/15mL

• Indications of Tysabri (Natalizumab):

  • Multiple sclerosis:

    • It can be used as monotherapy for MS.
    • It can be used in clinically isolated syndrome (CIS), relapsing MS, relapsing-remitting MS, and active secondary progressive disease.
    • Dose: 300 mg IV in infusion form every 4 weeks.
    • Risk-benefit must be considered as it can cause progressive multifocal leukoencephalopathy.

  • Crohn’s disease:

    • It is used in moderate to severe Crohn’s disease in patients who are intolerant or have an inadequate response to conventional therapies like steroids or TNF inhibitors.
    • Dose: 300mg in infusion form every 4 weeks.

  • Dosing considerations:

    • This drug should only be used in patients who are intolerant to conventional therapies or there was an inadequate response
    • It increases the risk of PML, especially if previously patient has been on immunosuppressants.
    • It is not advisable to use other immunosuppressants like cyclophosphamide, Mycophenolate mofetil (MMF), and 6-mercaptopurine (6-MP) concomitantly.

• Tysabri Interactions:

  • No severe interactions have been reported
  • However, alternatives should be used when other monoclonal antibodies are being considered.

• Side effects of Tysabri (Natalizumab):

  • Fatigue
  • Diarrhea
  • Toothaches
  • Menstrual irregularities
  • Increased urinary frequency
  • Sinusitis
  • Vaginitis
  • Arthralgias
  • Cough
  • Viral illnesses
  • Rash
  • Vertigo
  • Epigastric discomfort
  • UTIs
  • Oral ulcers
  • Post-marketing it has been noted to cause hemolytic anemia in a few cases.

• Cost of Tysabri (Natalizumab):

  • A single vial of 15 ml costs around USD 8000 per injection.