indication

For treatment of multiple sclerosis.

pharmacology

In multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells, and their counter-receptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be a secondary result of its blockade of the molecular interaction of a 4b 1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. α4-integrin is required for white blood cells to move into organs, therefore, natalizumab prevents these immune cells from crossing blood vessel walls to reach affected organs thereby decreasing inflamation.

mechanism of action

Binds to the α4-subunit of α4b 1 and α4b 7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s).

biotransformation

Most likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.

half life

11 ± 4 days

drug interactions

Bleomycin: Immunosuppressants like bleomycin may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.

Carboplatin: Immunosuppressants such as natalizumab may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.

Carmustine: Immunosuppressants such as carmustine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.

Chlorambucil: Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.

Cisplatin: Immunosuppressants such as cisplatin may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.

Cladribine: Immunosuppressants such as cladribine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.

Clofarabine: Immunosuppressants such as clofarabine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.

Tacrolimus: Tacrolimus may increase the toxic/adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.

Temozolomide: The immunosuppressant, Temozolomide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.

Temsirolimus: Temsirolimus may increase the toxicity of Natalizumab. Concomitant therapy should be avoided.

Teniposide: The immunosuppressant, Teniposide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.

Thalidomide: Thalidomide may increase the adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.

Thioguanine: The immunosuppressant, Thioguanine, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.

Thiotepa: The immunosuppressant, Thiotepa, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.

Topotecan: The immunosuppressant, Topotecan, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.

Tositumomab: The immunosuppressant, Tositumomab, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Tretinoin: Oral tretinoin may increase the adverse/toxic effects of Natalizumab. Concurrent therapy should be avoided.

Valrubicin: Valrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.

Vinblastine: Concomitant Vinblastine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.

Vincristine: Concomitant Vincristine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.

Vinorelbine: Concomitant Vinorelbine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.