DRUG STUDY AND INFORMATION FORM Generic Name: Rituximab Trade Name: Rituxan, MabThera Drug Class: Monoclonal

Antibody (Unarmed) Structure/Chemistry: Chimeric (mouse/human composite)

Pharmacodynamics

Mechanism of Action: Binds to CD20 on B cells (expressed on B cells ranging from pre-B cells to plasma cells) which has variable effects on cell cycle progression. Binding of the antiCD20 antibody generates transmembrane signals through serine/tyrosine activation, induction of c-myc oncogene expression, and expression of MHC II. It also may regulate transmembrane Ca2+ conductance through its function as a Ca2+ channel. It is unclear which of these mechanisms is responsible for rituximabs activity.

Pharmacologic Effects: Targets the CD20 B cell antigen. Causes effects by antibodydependent cellular cytotoxicity, complement-dependent cytotoxicity, and apoptosis (induced by antibody binding). Approved for treating indolent lymphomas and significantly enhances response and survival in combination with chemotherapy for the initial treatment of large B cell lymphoma.

Drug Resistance or Tolerance: Downregulation of CD20, impaired antibody-dependent cellular cytotoxicity, decreased complement activation, limited effects on signaling and induction of apoptosis, and inadequate blood levels.

Pharmacokinetics

Absorption: Administered by IV infusion as a single agent or in combinations at a dose of 375 mg/m2. As a single agent, given weekly for 4 weeks with maintenance dosing every 3-6 months. In combination regimens, given every 3-4 weeks, with chemotherapy, for up to eight doses. For first infusion, slow administration to prevent hypersensitivity reactions. Distribution:

Elimination: t1/2 of 22 days.

Metabolism:

Adverse Side Effects/Toxicity: Patients with large counts of tumor cells (as in CLL) are at increased risk of tumor lysis syndrome (need tumor lysis prophylaxis treatment prior to administration). Infusional reactions can be life-threatening, but with pretreatment are usually mild and limited to fever, chills, throat itching, urticaria, and mild hypotension. May develop severe mucocutaneous skin reactions (such as Stevens-Johnson syndrome). May cause reactivation of Hepatitis B or JC virus (screen for Hep B before treatment). Also may cause B cell depletion and late-onset neutropenia. Drug Interactions: Pre-treatment with anti-histamines, acetaminophen, and glucocorticoids decrease the risk of hypersensitivity reactions.

Therapeutic uses: Relapsed indolent lymphomas, large B cell lymphoma, good for several other indolent B cell non-Hodgkins lymphomas. Also used for autoimmune diseases

Miscellaneous: Monoclonal antibodies with names ending in ximab have chimeric (mouse/human) antibodies while those with names ending in umab have fully humanized antibodies.