Ocrelizumab

OCREVUS is indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults Primary progressive MS, in adults Relapsing-remitting MS, in pediatric patients 10 years of age and older who weigh 25 kg or more. OCREVUS is a CD20-directed cytolytic antibody indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Primary progressive MS, in adults. Relapsing-remitting MS, in pediatric patients 10 years of age and older who weigh 25 kg or more

The precise mechanism by which ocrelizumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.

Before initiating OCREVUS, screen for Hepatitis B virus and obtain serum quantitative immunoglobulins, aminotransferases, alkaline phosphatase, and bilirubin. Pre-medicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion. Administer OCREVUS by intravenous infusion. Adults and pediatric patients (10 years of age and older), who weigh 35 kg or more: Start dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion. Subsequent doses: 600 mg intravenous infusion every 6 months. Pediatric patients (10 years of age and older) who weigh 25 kg to less than 35 kg: Start dose: 150 mg intravenous infusion, followed two weeks later by a second 150 mg intravenous infusion. Subsequent doses: 300 mg intravenous infusion every 6 months. Must be diluted prior to administration.

OCREVUS is contraindicated in patients with: Active HBV infection A history of life-threatening infusion reaction to OCREVUS Active hepatitis B virus infection. History of life-threatening infusion reaction to OCREVUS

Infusion Reactions: Management recommendations for infusion reactions depend on the type and severity of the reaction. Permanently discontinue OCREVUS if a life-threatening or disabling infusion reaction occurs. Infections: Serious, including life-threatening and fatal infections, have occurred. Delay OCREVUS administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with OCREVUS and after discontinuation, until B-cell repletion. Progressive Multifocal Leukoencephalopathy (PML): Withhold OCREVUS at the first sign or symptom suggestive of PML. Reduction in Immunoglobulins: Monitor the level of immunoglobulins at the beginning of treatment.

The following serious adverse reactions are discussed elsewhere in the labeling: Infusion Reactions Infections Progressive Multifocal Leukoencephalopathy Reduction in Immunoglobulins Malignancies Immune-Mediated Colitis Liver Injury The most common adverse reactions were: RMS (incidence ≥10% and > REBIF ® ): upper respiratory tract infections and infusion reactions. PPMS (incidence ≥10% and > placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections. RRMS in pediatric patients 10 years of age and older: Adverse reactions were consistent with those observed in adults with RMS

Immunosuppressive or Immune-Modulating Therapies The concomitant use of OCREVUS and other immune-modulating or immunosuppressive therapies, including immunosuppressant doses of corticosteroids, is expected to increase the risk of immunosuppression. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with OCREVUS. When switching from drugs with prolonged immune effects, such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone, consider the duration and mode of action of these drugs because of additive immunosuppressive effects when initiating OCREVUS.

Store OCREVUS vials at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze or shake.