6 months after the last dose of TRUXIMA due to the potential forserious adverse reactions in breastfed infants.
8.3 Females and Males of Reproductive Potential
Rituximab products can cause fetal harm [see Use in Specific Populations (8.1)].
Contraception
Females
Females of childbearing potential should use effective contraception while receivingTRUXIMA and for 12 months following treatment.
8.4 Pediatric Use
The safety and effectiveness of rituximab in pediatric patients have not been established.
Hypogammaglobulinemia has been observed in pediatric patients treated with rituximab.
8.5 Geriatric Use
Low-Grade or Follicular Non-Hodgkin’s Lymphoma
Patients with previously untreated follicular NHL eva luated in Study 5 were randomized torituximab as single-agent maintenance therapy (n=505) or observation (n=513) after achieving aresponse to rituximab in combination with chemotherapy. Of these, 123 (24%) patients in therituximab arm were age 65 or older. No overall differences in safety or effectiveness wereobserved between these patients and younger patients. Other clinical studies of rituximab inlow-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers ofpatients aged 65 and over to determine whether they respond differently from younger subjects.
11 DESCRIPTION
Rituximab-abbs is a genetically engineered chimeric murine/human monoclonal IgG1 kappaantibody directed against the CD20 antigen. Rituximab-abbs has an approximate molecularweight of 145 kD.
Rituximab-abbs is produced by mammalian cell (Chinese Hamster Ovary) suspension culture in
a nutrient medium.
TRUXIMA (rituximab-abbs) injection is a sterile, clear to opalescent, colorless to pale yellow,preservative-free solution for intravenous infusion. TRUXIMA is supplied at a concentrationof 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Each mL of solutioncontains 10 mg rituximab-abbs, polysorbate 80 (0.7 mg), sodium chloride (9 mg), tri-sodiumcitrate dihydrate (7.35 mg), and Water for Injection, USP. The pH is 6.5.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Rituximab-abbs is a monoclonal antibody. Rituximab products target the CD20 antigenexpressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximabproducts mediate B-cell lysis. Possible mechanisms of cell lysis include complement dependentcytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC).
12.2 Pharmacodynamics
Non-Hodgkin’s Lymphoma (NHL)
In NHL patients, administration of rituximab resulted in depletion of circulating and tissue-basedB cells. Among 166 patients in Study 1 (NCT000168740), circulating CD19-positive B cellswere depleted within the first three weeks with sustained depletion for up to 6 to 9 months posttreatment in 83% of patients. B-cell recovery began at approximately 6 months and median Bcelllevels returned to normal by 12 months following completion of treatment.
There were sustained and statistically significant reductions in both IgM and IgG serum levelsobserved from 5 through 11 months following rituximab administration; 14% of patients hadIgM and/or IgG serum levels below the normal range.
12.3 Pharmacokinetics
Non-Hodgkin’s Lymphoma (NHL)
Pharmacokinetics were characterized in 203 NHL patients receiving 375 mg/m2 rituximabweekly by intravenous infusion for 4 doses. Rit |
