Treatment for Hematological cancers
Zytux is a biosimilar product with the generic name of
Rituximab and is used for treatment of some types of cancer.
It is a chimeric monoclonal antibody against CD20 antigens presents on surface of lymphocyte cells.
Zytux is a genetically engineered human-mouse chimeric monoclonal antibody
produced by Chinese Hamster Ovary (CHO) cells in suspension and purified by some steps of chromatography.
It is a fusion of the light and heavy chain variable domains of a murine monoclonal anti-CD20 antibody and human
kappa light-chain and gamma 1 heavy-chain constant regions. Active ingredient of Zytux, Rituximab, consists of two heavy
chains of 451 amino acids and two light chains of 213 amino acids, with an approximate molecular weight of 148 kDa.
Rituximab binds to the target CD20 antigen via the variable murine regions, while the remainder of the antibody
interacts with human immune-effector mechanisms to kill the target cells.
Recommended International Nonproprietary Name (INN)
Chemical Abstracts Service (CAS) registry number.
Anatomical Therapeutic Chemical (ATC)
Mechanism of action
Rituximab is a monoclonal chimeric (mouse/human)
antibody which binds specifically to the transmembrane antigen CD20 located on pre-B and mature
B lymphocytes, but not on hematopoietic stem cells, pro-B cells, normal plasma cells or other normal tissue.
The antigen is expressed on >95% of all B cell non-Hodgkin’s lymphomas. After antibody binding,
CD20 does not internalize, nor is it shed from the cell membrane.CD20 does not circulate in plasma
as free antigen and thus does not compete
for antibody binding. Studies
to date have found no connection between the intensity of CD20 expression on the malignant cells and treatment response.
Rituximab binds to the CD20 antigen on
B lymphocytes and causes B cell lysis. Possible mechanisms of cell lysis are complement-dependent
cytotoxicity (CDC) together with antibody-dependent cellular cytotoxicity (ADCC) and induction of apoptosis.
Peripheral B cell counts fell below normal after the first dose of Zytux.
In patients treated for hematological malignancy, B cells began to regenerate within 6 months of completing therapy,
reverting to normal within 9 to 12 months of completing therapy. Rituximab
sensitizes drug-resistant human B cell lymphoma lines to the cytotoxic effect of some chemotherapy agents.
- Treatment of patients with CD20-positive follicular non-Hodgkin’s lymphoma
(stage III –IV) who have relapsed after, or failed to respond to, chemotherapy.
- Treatment of previously untreated
patients with CD20-positive
follicular non-Hodgkin’s lymphoma (stage III –IV) in combination with
standard CVP chemotherapy (8 cycles of cyclophosphamide, vincristine and prednisone).
- Treatment of patients with CD20-positive
diffuse large B cell non-Hodgkin’s lymphoma (DLBCL)
in combination with standard CHOP (8 cycles of cyclophosphamide , doxorubicin , vincristine and prednisone).
- Maintenance therapy of patients with relapsed or refractory CD20-positive follicular non-Hodgkin’s lymphoma
(stage III –IV) who have responded to induction therapy with CHOP (6 cycles of cyclophosphamide ,doxorubicin ,vincristine and prednisone)
or R-CHOP(6 cycles of CHOP plus Zytux)
Chronic Lymphocytic Leukemia (CLL)
Zytux is indicated for the treatment of patients with previously
untreated or previously treated B-cell chronic lymphocytic leukemia (Binet Stage B or C) in combination with fludarabine and cyclophosphamide.
The use of Zytux in CLL patients is based on an improvement in progression-free survival.
Zytux is supplied as a sterile, clear, colorless, preservative-free liquid concentrate
for intravenous (IV) infusion. It is provided in two dosages, 100 mg and 500 mg vials.
Active substance: rituximab
Excipients: sodium citrate, polysorbate 80, sodium chloride and water for injection.
PHARMACEUTICAL FORM AND AMOUNT OF ACTIVE INGREDIENT PER UNIT:
Zytux 100: Each 10 ml vial contains 100 mg rituximab (rituximab conc. 10mg/ml)
Zytux 500: Each 50 ml vial contains 500 mg rituximab (rituximab conc. 10mg/ml)