Interactions between rebif(interferon beta-1a) and Natalizumab (natalizumab)
interferon beta-1a and natalizumab (Major Drug-Drug)
GENERALLY AVOID: Use of natalizumab in combination with immunomodulatory agents such as interferon beta has resulted in rare cases of progressive multifocal leukoencephalopathy (PML), a severely disabling, potentially fatal opportunistic viral infection of the brain. The mechanism has not been described. In clinical trials, PML occurred in two of 1869 patients with multiple sclerosis treated with natalizumab for a median of 120 weeks, and both were receiving concomitant interferon beta-1a therapy. However, the number of cases is too few and the number of patients treated too small to rule out the possibility that PML may also occur with natalizumab monotherapy. Pharmacokinetically, coadministration with interferon beta-1a has been shown to increase the plasma concentrations of natalizumab. According to natalizumab product labeling, interferon beta-1a (30 mcg intramuscularly once a week) reduced the clearance of natalizumab by approximately 30% following multiple-dosing. However, the natalizumab-related adverse event profile in this study was not significantly different than that in another study where patients did not receive concomitant interferon beta-1a.
MANAGEMENT: Although data are limited with respect to the risk of PML, the use of natalizumab in combination with immunomodulatory agents including interferon beta should generally be avoided. All patients treated with natalizumab should be monitored closely and the drug discontinued immediately at the first sign or symptom suggestive of PML. However, it is not known if early detection of PML and discontinuation of natalizumab will mitigate the disease.
