Hyaluronidase (human recombinant) and Ocrelizumab

OCREVUS ZUNOVO 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 OCREVUS ZUNOVO 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

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. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in OCREVUS ZUNOVO acts transiently and locally.

OCREVUS ZUNOVO should be administered by a healthcare professional. For subcutaneous use in the abdomen only. OCREVUS ZUNOVO has different dosage and administration instructions than intravenous ocrelizumab. Before initiating OCREVUS ZUNOVO, screen for Hepatitis B virus and obtain serum quantitative immunoglobulins, aminotransferases, alkaline phosphatase, and bilirubin. Pre-medicate orally with dexamethasone (or an equivalent corticosteroid) and an antihistamine (e.g., desloratadine) at least 30 minutes prior to each injection. Administer 23 mL of OCREVUS ZUNOVO (920 mg ocrelizumab and 23,000 units hyaluronidase) subcutaneously in the abdomen over approximately 10 minutes every 6 months. Monitor patients closely during all injections, for at least one hour after the initial injection, and for at least 15 minutes after subsequent injections

OCREVUS ZUNOVO is contraindicated in patients with: Active HBV infection A history of life-threatening administration reaction to ocrelizumab A history of hypersensitivity to ocrelizumab, hyaluronidase, or any component of OCREVUS ZUNOVO. Active hepatitis B virus infection. History of life-threatening administration reactions to ocrelizumab. History of hypersensitivity to ocrelizumab, hyaluronidase, or to any component of OCREVUS ZUNOVO

Injection Reactions: Management recommendations for injection reactions depend on the type and severity of the reaction. Permanently discontinue OCREVUS ZUNOVO if a life-threatening injection reaction occurs. Infections: Serious, including life-threatening and fatal, infections have occurred in patients treated with ocrelizumab. Delay OCREVUS ZUNOVO 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 ZUNOVO and after discontinuation, until B-cell repletion. Progressive Multifocal Leukoencephalopathy (PML): Withhold OCREVUS ZUNOVO 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 in greater detail in other sections of the labeling: Injection Reactions Infections Progressive Multifocal Leukoencephalopathy Reduction in Immunoglobulins Malignancies Immune-Mediated Colitis Liver Injury The most common adverse reactions in patients treated with intravenous ocrelizumab 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. The most common adverse reaction observed with OCREVUS ZUNOVO in patients with RMS and PPMS was injection reactions (incidence of 49%)

Immunosuppressive or Immune-Modulating Therapies The concomitant use of OCREVUS ZUNOVO 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 ZUNOVO. 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 ZUNOVO.

Store OCREVUS ZUNOVO vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake. If necessary, OCREVUS ZUNOVO can be removed and placed back into the refrigerator. Unopened OCREVUS ZUNOVO vials may be stored in the original carton for a cumulative time of up to 12 hours without refrigeration at a temperature up to 25°C (77°F).