Hyaluronidase (human recombinant) and Rituximab

RITUXAN HYCELA is a combination of rituximab, a CD20-directed cytolytic antibody, and hyaluronidase human, an endoglycosidase, indicated for the treatment of adult patients with: Follicular Lymphoma (FL). Relapsed or refractory, follicular lymphoma as a single agent Previously untreated follicular lymphoma in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy Diffuse Large B-cell Lymphoma (DLBCL).

Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). 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 human increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan. In the doses administered, hyaluronidase human in RITUXAN HYCELA acts locally.

For subcutaneous use only. All patients must receive at least one full dose of a rituximab product by intravenous infusion before receiving RITUXAN HYCELA by subcutaneous injection. FL/DLBCL: Administer 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously according to recommended schedule. CLL: Administer 1,600 mg/26,800 Units (1,600 mg rituximab and 26,800 Units hyaluronidase human) subcutaneously according to recommended schedule. Premedicate with acetaminophen and antihistamine before each dose, in addition, consider premedication with glucocorticoids. Administer specified volume into subcutaneous tissue of abdomen: 11.7 mL from 1,400 mg/23,400 Units vial over approximately 5 minutes. 13.4 mL from 1,600 mg/26,800 Units vial over approximately 7 minutes. Observe 15 minutes following administration

None None.

Boxed warning: Severe mucocutaneous reactions, some with fatal outcomes. Hepatitis B virus reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Progressive multifocal leukoencephalopathy resulting in death. Severe Mucocutaneous Reactions Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab-containing products, including RITUXAN HYCELA. Hypersensitivity and other administration reactions: Local cutaneous reactions may occur more than 24 hours after administration. Interrupt injection if severe reaction develops. Premedicate before injection. Tumor lysis syndrome: Administer aggressive intravenous hydration, anti hyperuricemic agents, monitor renal function. Infections: Withhold and institute appropriate anti-infective therapy. Cardiac adverse reactions: Discontinue in case of serious or life-threatening events.

The following clinically significant adverse reactions are described elsewhere in the labeling: Mucocutaneous reactions Hepatitis B reactivation including fulminant hepatitis Progressive multifocal leukoencephalopathy Hypersensitivity and other administration reactions Tumor lysis syndrome Infections Cardiac arrhythmias Renal toxicity Bowel obstruction and perforation Most common adverse reactions (incidence of ≥ 20%) are: FL: infections, neutropenia, nausea, constipation, cough, and fatigue DLBCL: infections, neutropenia, alopecia, nausea, and anemia CLL: infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema

Renal toxicity when used in combination with cisplatin.

Store RITUXAN HYCELA vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.