Re: [MOL] No Subject [00292] Medicine On Line


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Re: [MOL] No Subject



Hi Michael!  Welcome to our wonderful forum, we are sorry to hear about your
father; but keep in mind that there are more people living with cancer today
than dying.  That cancer rates are continually going down and that there is
always hope.
Warmly, lillian

We invite you to take a look at our Album.
www.angelfire.com/sc/molangels/index.html

  ( Very informational, good tips, Molers pictures, art work and much
more....

http://askjeeves.com/main/metaAnswer.asp?  Go to this site and type in Non
Hodgkin's Laphomia-  You will get a lot of good information.




Full Prescribing Information
DESCRIPTION OF RITUXAN®
CLINICAL PHARMACOLOGY
CLINICAL STUDIES
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
 PRECAUTIONS
ADVERSE REACTIONS
OVERDOSAGE
DOSAGE AND ADMINISTRATION
HOW SUPPLIED
REFERENCES



WARNINGS
Infusion-related reactions: Infusion-related deaths (death within 24 hours
of infusion) have been reported at a rate of approximately 0.04-0.07% (4-7
per 10,000 patients treated). These events appear as manifestations of an
infusion-related complex and include hypoxia, pulmonary infiltrates, adult
respiratory distress syndrome, myocardial infarction, ventricular
fibrillation or cardiogenic shock. Nearly all fatal infusion-related events
occurred in association with the first infusion. In the reported cases, the
following factors were more frequently associated with fatal outcomes:
women, patients with pulmonary infiltrates, and patients with CLL or mantle
cell lymphoma (see WARNINGS).
Regarding the management of infusion-related reactions:


Patients who develop clinically significant cardiopulmonary events should
have RITUXAN infusion discontinued and receive medical treatment.
Patients with pre-existing cardiac and pulmonary conditions or those with
prior clinically significant cardiopulmonary adverse events should be
monitored during and after subsequent infusions of RITUXAN.
Patients with high numbers of circulating malignant cells (25,000/mm3) with
or without other evidence of high tumor burden should be more closely
monitored for infusion reactions and tumor lysis syndrome.
Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with
instances of fatal outcome has been reported in the setting of TLS.
Assessment of serum electrolytes and renal function is indicated in patients
with rapid decreases in tumor volume (see WARNINGS).


DESCRIPTION
The RITUXAN® (Rituximab) antibody is a genetically engineered chimeric
murine/human monoclonal antibody directed against the CD20 antigen found on
the surface of normal and malignant B lymphocytes. The antibody is an IgG1
kappa immunoglobulin containing murine light- and heavy- chain variable
region sequences and human constant region sequences. Rituximab is composed
of two heavy chains of 451 amino acids and two light chains of 213 amino
acids (based on cDNA analysis) and has an approximate molecular weight of
145 kD. Rituximab has a binding affinity for the CD20 antigen of
approximately 8.0 nM.
The chimeric anti-CD20 antibody is produced by mammalian cell (Chinese
Hamster Ovary) suspension culture in a nutrient medium containing the
antibiotic gentamicin. Gentamicin is not detectable in the final product.
The anti-CD20 antibody is purified by affinity and ion exchange
chromatography. The purification process includes specific viral
inactivation and removal procedures. Rituximab drug product is manufactured
from either bulk drug substance manufactured by Genentech, Inc. (US License
No. 1048), or utilizing formulated bulk Rituximab supplied by IDEC
Pharmaceuticals Corporation (US License No. 1235) under a shared
manufacturing arrangement.

RITUXAN is a sterile, clear, colorless, preservative-free liquid concentrate
for intravenous (IV) administration. RITUXAN is supplied at a concentration
of 10 mg/mL in either 100 mg (10 mL) or 500 mg (50 mL) single-use vials. The
product is formulated for intravenous administration in 9.0 mg/mL sodium
chloride, 7.35 mg/mL sodium citrate dihydrate, 0.7 mg/mL polysorbate 80, and
Sterile Water for Injection. The pH is adjusted to 6.5.




CLINICAL PHARMACOLOGY
General
Rituximab binds specifically to the antigen CD20 (human
B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic
transmembrane protein with a molecular weight of approximately 35 kD located
on pre-B and mature B lymphocytes.1,2 The antigen is also expressed on >90%
of B-cell non-Hodgkin's lymphomas (NHL)3 but is not found on hematopoietic
stem cells, pro-B cells, normal plasma cells or other normal tissues.4 CD20
regulates an early step(s) in the activation process for cell cycle
initiation and differentiation,4 and possibly functions as a calcium ion
channel.5 CD20 is not shed from the cell surface and does not internalize
upon antibody binding.6 Free CD20 antigen is not found in the circulation.2
Preclinical Pharmacology and Toxicology
Mechanism of Action: The Fab domain of Rituximab binds to the CD20 antigen
on B lymphocytes, and the Fc domain recruits immune effector functions to
mediate B-cell lysis in vitro. Possible mechanisms of cell lysis include
complement-dependent cytotoxicity (CDC)7 and antibody-dependent cell
mediated cytotoxicity (ADCC). The antibody has been shown to induce
apoptosis in the DHL-4 human B-cell lymphoma line.8
Normal Tissue Cross-reactivity: Rituximab binding was observed on lymphoid
cells in the thymus, the white pulp of the spleen, and a majority of B
lymphocytes in peripheral blood and lymph nodes. Little or no binding was
observed in the non-lymphoid tissues examined.

Human Pharmacokinetics/Pharmacodynamics
In patients given single doses at 10, 50, 100, 250 or 500 mg/m2 as an IV
infusion, serum levels and the half-life of Rituximab were proportional to
dose. In nine patients given 375 mg/m2 as an IV infusion for four doses, the
mean serum half-life was 59.8 hours (range 11.1 to 104.6 hours) after the
first infusion and 174 hours (range 26 to 442 hours) after the fourth
infusion. The wide range of half-lives may reflect the variable tumor burden
among patients and the changes in CD20 positive (normal and malignant)
B-cell populations upon repeated administrations.
Rituximab at a dose of 375 mg/m2 was administered as an IV infusion at
weekly intervals for four doses to 166 patients. The peak and trough serum
levels of Rituximab were inversely correlated with baseline values for the
number of circulating CD20 positive B cells and measures of disease burden.
Median steady-state serum levels were higher for responders compared to
nonresponders; however, no difference was found in the rate of elimination
as measured by serum half-life. Serum levels were higher in patients with
International Working Formulation (IWF) subtypes B, C, and D as compared to
those with subtype A. Rituximab was detectable in the serum of patients
three to six months after completion of treatment.

The pharmacokinetic profile of Rituximab when administered as six infusions
of 375 mg/m2 in combination with six cycles of CHOP chemotherapy was similar
to that seen with Rituximab alone.

Administration of RITUXAN® (Rituximab) resulted in a rapid and sustained
depletion of circulating and tissue-based B cells. Lymph node biopsies
performed 14 days after therapy showed a decrease in the percentage of B
cells in seven of eight patients who had received single doses of Rituximab
100 mg/m2. 9 Among the 166 patients in the pivotal study, circulating B
cells (measured as CD19 positive cells) were depleted within the first three
doses with sustained depletion for up to 6 to 9 months post treatment in 83%
of patients. One of the responding patients (1%), failed to show significant
depletion of CD19 positive cells after the third infusion of Rituximab as
compared to 19% of the nonresponding patients. B cell recovery began at
approximately six months following completion of treatment. Median B cell
levels returned to normal by twelve months following completion of
treatment.

There were sustained and statistically significant reductions in both IgM
and IgG serum levels observed from 5 through 11 months following Rituximab
administration. However, only 14% of patients had reductions in IgM and/or
IgG serum levels, resulting in values below the normal range.

CLINICAL STUDIES
A multicenter, open-label, single-arm study was conducted in 166 patients
with relapsed or refractory low-grade or follicular B-cell NHL who received
375 mg/m2 of RITUXAN® (Rituximab) given as an IV infusion weekly for four
doses. Patients with tumor masses >10 cm or with >5,000 lymphocytes/µL in
the peripheral blood were excluded from the study. The overall response rate
(ORR) was 48% (80/166) with a 6% (10/166) complete response (CR) and a 42%
(70/166) partial response (PR) rate. Disease-related signs and symptoms
(including B-symptoms) were present in 23% (39/166) of patients at study
entry and resolved in 64% (25/39) of those patients. The median time to
onset of response was 50 days and the median duration of response is
projected to be 10 to 12 months.
In a multivariate analysis, the ORR was higher in patients with IWF B, C,
and D histologic subtypes as compared to IWF subtype A (58% vs. 12%), higher
in patients whose largest lesion was <5 cm vs. >7 cm in greatest diameter
(53% vs. 38%), and higher in patients with chemosensitive relapse as
compared to chemoresistant (defined as duration of response <3 months)
relapse (53% vs. 36%). ORR in patients previously treated with autologous
bone marrow transplant was 78% (18/23). The following factors were not
associated with a lower response rate: age  60 years, extranodal disease,
prior anthracycline therapy, and bone marrow involvement.

In a second multicenter, multiple-dose study, 37 patients with relapsed or
refractory B-cell NHL received 375 mg/m2 of RITUXAN as an IV infusion once
weekly for four doses. 10,11 The ORR was 46% with a median duration of
response of 8.6 months (range 2.6 to 26.2+). Single doses of up to 500 mg/m2
were well tolerated. 9

Twenty patients have received two courses and one patient has received three
courses of RITUXAN as four weekly infusions of 375 mg/m2 per infusion. The
percentage of patients reporting adverse events upon retreatment was similar
to that reported following the first course, although the incidence of
specific adverse events differed (see ADVERSE REACTIONS). All patients had
obtained an objective clinical response (CR or PR) to the first course of
RITUXAN; upon retreatment, 6 of 12 patients evaluable for response obtained
a complete or partial remission.

Twenty-nine patients with relapsed or refractory, bulky (single lesion of
>10 cm in diameter), low-grade NHL received 375 mg/m2 of RITUXAN as four
weekly infusions. The overall incidence of adverse events and the incidence
of Grade 3 and 4 adverse events was higher in patients with bulky disease
than in patients with non-bulky disease (see ADVERSE REACTIONS). Ten of 21
patients evaluable for response have obtained a complete or partial
remission.

INDICATIONS AND USAGE
RITUXAN® (Rituximab) is indicated for the treatment of patients with
relapsed or refractory low-grade or follicular, CD20 positive, B-cell
non-Hodgkin's lymphoma.



CONTRAINDICATIONS
RITUXAN® (Rituximab) is contraindicated in patients with known Type I
hypersensitivity or anaphylatic reactions to murine proteins or to any
component of this product. (See WARNINGS.)



WARNINGS (see BOXED WARNINGS)
Infusion-Related Events (see BOXED WARNING): An infusion-related symptom
complex consisting of fever and chills/rigors occurred in the majority of
patients during the first RITUXAN® (Rituximab) infusion. Other frequent
infusion-related symptoms included nausea, urticaria, fatigue, headache,
pruritus, bronchospasm, dyspnea, sensation of tongue or throat swelling
(angioedema), rhinitis, vomiting, hypotension, flushing, and pain at disease
sites. These reactions generally occurred within 30 minutes to 2 hours of
beginning the first infusion, and resolved with slowing or interruption of
the RITUXAN infusion and with supportive care (diphenhydramine,
acetaminophen, IV saline, and vasopressors). RITUXAN infusion should be
interrupted for severe reactions. In most cases, the infusion can be resumed
at a 50% reduction in rate (e.g., from 100 mg/hr to 50 mg/hr) when symptoms
have completely resolved. In clinical studies, the incidence of
infusion-related events decreased from 80% (7% Grade 3/4) during the first
infusion to approximately 40% (5% to 10% Grade 3/4) with subsequent
infusions. Mild to moderate hypotension requiring interruption of RITUXAN
infusion with or without the administration of IV saline occurred in 32
(10%) patients. Angioedema was reported in 41 (13%) patients and was serious
in one patient. Bronchospasm occurred in 24 (8%) patients; one-quarter of
these patients were treated with bronchodilators.
Tumor Lysis Syndrome (see BOXED WARNING): TLS, characterized by rapid
reduction in tumor volume, renal insufficiency, hyperkalemia, hypocalcemia,
hyperuricemia, or hyperphosphatasemia, has been reported within 12 to 24
hours after the first RITUXAN infusion at a reported rate of 0.04%-0.05%.
The risks of TLS appear to be higher in patients with high numbers of
circulating malignant cells. Correction of electrolytes abnormalities,
monitoring of renal function and fluid balance, and supportive care,
including dialysis, should be initiated as indicated. Following complete
resolution of the complications of TLS, RITUXAN has been tolerated when
re-administered in conjunction with prophylactic therapy for TLS in a
limited number of cases.

General
RITUXAN® (Rituximab) is associated with hypersensitivity reactions which may
respond to adjustments in the infusion rate. Hypotension, bronchospasm, and
angioedema have occurred in association with RITUXAN infusion as part of an
infusion-related symptom complex. RITUXAN infusion should be interrupted for
severe reactions and can be resumed at a 50% reduction in rate (e.g., from
100 mg/hr to 50 mg/hr) when symptoms have completely resolved. Treatment of
these symptoms with diphenhydramine and acetaminophen is recommended;
additional treatment with bronchodilators or IV saline may be indicated. In
most cases, patients who have experienced non-life-threatening reactions
have been able to complete the full course of therapy. (See DOSAGE and
ADMINISTRATION.) Medications for the treatment of hypersensitivity
reactions, e.g., epinephrine, antihistamines and corticosteroids should be
available for immediate use in the event of a reaction during
administration.

Cardiovascular
Infusions should be discontinued in the event of serious or life-threatening
cardiac arrhythmias. Patients who develop clinically significant arrhythmias
should undergo cardiac monitoring during and after subsequent infusions of
RITUXAN. Patients with preexisting cardiac conditions including arrhythmias
and angina have had recurrences of these events during RITUXAN therapy and
should be monitored throughout the infusion and immediate post-infusion
period.






PRECAUTIONS
Laboratory Monitoring: Complete blood counts (CBC) and platelet counts
should be obtained at regular intervals during RITUXAN® (Rituximab) therapy
and more frequently in patients who develop cytopenias (see ADVERSE
REACTIONS).
Drug/Laboratory Interactions: There have been no formal drug interaction
studies performed with RITUXAN.

HAMA/HACA Formation: Human anti-murine antibody (HAMA) was not detected in
67 patients evaluated. Less than 1.0% (3/355) of patients evaluated for
human anti-chimeric antibody (HACA) were positive. Patients who develop
HAMA/HACA titers may have allergic or hypersensitivity reactions when
treated with this or other murine or chimeric monoclonal antibodies.

Immunization: The safety of immunization with any vaccine, particularly live
viral vaccines, following RITUXAN therapy has not been studied. The ability
to generate a primary or anamnestic humoral response to any vaccine has also
not been studied.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No long-term animal
studies have been performed to establish the carcinogenic or mutagenic
potential of RITUXAN, or to determine its effects on fertility in males or
females. Individuals of childbearing potential should use effective
contraceptive methods during treatment and for up to 12 months following
RITUXAN therapy.

Pregnancy Category C: Animal reproduction studies have not been conducted
with RITUXAN. It is not known whether RITUXAN can cause fetal harm when
administered to a pregnant woman or whether it can affect reproductive
capacity. Human IgG is known to pass the placental barrier, and thus may
potentially cause fetal B-cell depletion; therefore, RITUXAN should be given
to a pregnant woman only if clearly needed.

Nursing Mothers: It is not known whether RITUXAN is excreted in human milk.
Because human IgG is excreted in human milk and the potential for absorption
and immunosuppression in the infant is unknown, women should be advised to
discontinue nursing until circulating drug levels are no longer detectable.
(See CLINICAL PHARMACOLOGY.)

Pediatric Use: The safety and effectiveness of RITUXAN in pediatric patients
have not been established.




ADVERSE REACTIONS
Safety data, except where indicated, are based on 315 patients treated in
five single-agent studies of RITUXAN® (Rituximab). These include patients
with bulky disease (lesions >10 cm), those who have received more than one
course of RITUXAN, and patients receiving 375 mg/m2 for eight doses.
Infusion-Related Events: (See BOXED WARNING AND WARNINGS.)

Immunologic Events: RITUXAN induced B-cell depletion in 70 to 80% of
patients and was associated with decreased serum immunoglobulins in a
minority of patients. The incidence of infection did not appear to be
increased. During the treatment period, 50 out of 166 patients (30%) in the
pivotal trial developed 68 infectious events; six (9%) were Grade 3 in
severity and none were Grade 4 events. Of the six serious infectious events,
none were associated with neutropenia. The serious bacterial events included
sepsis due to Listeria (n=1), Staphylococcal bacteremia (n=1), and
polymicrobial sepsis (n=1). In the post treatment period (30 days to 11
months following the last dose), bacterial infections included sepsis (n=1);
significant viral infections included Herpes simplex infections (n=2) and
Herpes zoster (n=3). Additional reports of focal bacterial infections,
sepsis, and viral infections have been received in the postmarketing
setting. Serious infections, including sepsis, have been reported in
patients with and without neutropenia.

Retreatment Events: Twenty-one patients have received more than one course
of RITUXAN. The percentage of patients reporting any adverse event upon
retreatment was similar to the percentage of patients reporting adverse
events upon initial exposure. The following adverse events were reported
more frequently in retreated subjects: asthenia, throat irritation,
flushing, tachycardia, anorexia, leukopenia, thrombocytopenia, anemia,
peripheral edema, dizziness, depression, respiratory symptoms, night sweats,
and pruritus.

Hematologic Events: Severe cytopenias were reported including
thrombocytopenia (1.3%), neutropenia (1.9%), and anemia (1.0%). A single
occurrence of transient aplastic anemia (pure red cell aplasia) and two
occurrences of hemolytic anemia following RITUXAN therapy were reported. In
addition, there have been rare postmarketing reports of prolonged
pancytopenia and marrow hypoplasia.

Cardiac Events (see BOXED WARNING): Four patients developed ventricular or
supraventricular arrhythmias and one patient developed angina in association
with the RITUXAN infusion. Rare, fatal cardiac failure with symptomatic
onset weeks after RITUXAN has also been reported. Patients who develop
clinically significant cardiopulmonary events should have RITUXAN infusion
discontinued.

Pulmonary Events (see BOXED WARNING): Three pulmonary events have been
reported in temporal association with RITUXAN infusion as a single agent:
acute, infusion-related bronchospasm, an acute pneumonitis presenting 1-4
weeks post-RITUXAN infusion, and bronchiolitis obliterans. The bronchiolitis
obliterans was associated with progressive pulmonary symptoms and culminated
in death several months following the last RITUXAN infusion. The safety of
resumption or continued administration of RITUXAN in patients with
pneumonitis or bronchiolitis obliterans is unknown.

Table 1
Adverse Events 5%
of Patients (N=315)
 Incidence
All Grades
 N %
Any Adverse Event 275 87

Body As A Whole
  Fever 154 49
  Chills 102 32
  Asthenia 49 16
  Headache 43 14
  Throat Irritation 19 6
  Abdominal Pain 18 6

Cardiovascular System
  Hypotension 32 10

Digestive System
  Nausea 55 18
  Vomiting 23 7

Hemic and Lymphatic System
  Leukopenia 33 11
  Thrombocytopenia 25 8
  Neutropenia 21 7

Metabolic and Nutritional System
  Angioedema 41 13

Musculo-Skeletal System
  Myalgia 21 7

Nervous System
  Dizziness 23 7

Respiratory System
  Rhinitis 25 8
  Bronchospasm 24 8

Skin and Appendages
  Pruritus 32 10
  Rash 31 10
  Urticaria 24 8


Severe and life-threatening (Grade 3 and 4) events were reported in 10%
(32/315) of patients. The following Grade 3 and 4 adverse events were
reported: neutropenia (1.9%), chills (1.6%), leukopenia and thrombocytopenia
(1.3% for each), hypotension, anemia, bronchospasm, and urticaria (1.0% for
each), headache, abdominal pain, and arrhythmia (0.6% for each), asthenia,
hypertension, nausea, vomiting, coagulation disorder, angioedema,
arthralgia, pain, rhinitis, increased cough, dyspnea, bronchiolitis
obliterans, hypoxia, asthma, pruritus, and rash (one patient each, 0.3%).

The following adverse events occurred in 1.0% but <5.0% of patients, in
order of decreasing incidence: flushing, arthralgia, diarrhea, anemia, cough
increase, hypertension, lacrimation disorder, pain, hyperglycemia, back
pain, peripheral edema, paresthesia, dyspepsia, chest pain, anorexia,
anxiety, malaise, tachycardia, agitation, insomnia, sinusitis,
conjunctivitis, abdominal enlargement, postural hypotension, LDH increase,
hypocalcemia, hypesthesia, respiratory disorder, tumor pain, pain at
injection site, bradycardia, hypertonia, nervousness, bronchitis, and taste
perversion.

Multisystem adverse events-The following serious adverse reactions have been
reported at a frequency of less than 0.1% in the postmarketing setting:

Body as a Whole: Lupus-like syndrome and serum sickness
Cardiovascular System: Systemic vasculitis
Musculoskeletal System: Polyarticular arthritis
Respiratory System: Pleuritis
Skin and Appendages: Severe bullous skin reactions (including toxic
epidermal necrolysis) and pemphigus; some with fatal outcome
Special Senses: Optic neuritis and uveitis

Several of these events were reported as individual components of
multisystem processes (e.g., optic neuritis in a patient with systemic
vasculitis, pleuritis in association with lupus-like syndrome, etc.) and
often in conjunction with rash and polyarthritis.

The proportion of patients reporting any adverse event was similar in
patients with bulky disease and those with lesions <10 cm in diameter.
However, the incidence of dizziness, neutropenia, thrombocytopenia, myalgia,
anemia and chest pain was higher in patients with lesions >10 cm. The
incidence of any Grade 3 and 4 event was higher (31% vs. 13%) and the
incidence of Grade 3 or 4 neutropenia, anemia, hypotension, and dyspnea was
also higher in patients with bulky disease compared with patients with
lesions <10 cm.


OVERDOSAGE
There has been no experience with overdosage in human clinical trials.
Single doses higher than 500 mg/m2 have not been tested.



DOSAGE AND ADMINISTRATION
Usual Dose:
The recommended dosage of RITUXAN® (Rituximab) is 375 mg/m2 given as an IV
infusion once weekly for four doses (Days 1, 8, 15, and 22). RITUXAN may be
administered in an outpatient setting. DO NOT ADMINISTER AS AN INTRAVENOUS
PUSH OR BOLUS. (See Administration.)

Instructions for Administration
Preparation for Administration: Use appropriate aseptic technique. Withdraw
the necessary amount of RITUXAN and dilute to a final concentration of 1 to
4 mg/mL into an infusion bag containing either 0.9% Sodium Chloride, USP, or
5% Dextrose in Water, USP. Gently invert the bag to mix the solution.
Discard any unused portion left in the vial. Parenteral drug products should
be inspected visually for particulate matter and discoloration prior to
administration.
RITUXAN solutions for infusion are stable at 2-8°C (36-46° F) for 24 hours
and at room temperature for an additional 12 hours. No incompatibilities
between RITUXAN and polyvinylchloride or polyethlene bags have been
observed.

Administration: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.
Hypersensitivity reactions may occur (see WARNINGS). Premedication
consisting of acetaminophen and diphenhydramine should be considered before
each infusion of RITUXAN. Premedication may attenuate infusion-related
events. Since transient hypotension may occur during RITUXAN infusion,
consideration should be given to withholding anti-hypertensive medications
12 hours prior to RITUXAN infusion.

First Infusion: The RITUXAN solution for infusion should be administered
intravenously at an initial rate of 50 mg/hr. RITUXAN should not be mixed or
diluted with other drugs. If hypersensitivity or infusion-related events do
not occur, escalate the infusion rate in 50 mg/hr increments every 30
minutes, to a maximum of 400 mg/hr. If hypersensitivity or an
infusion-related event develops, the infusion should be temporarily slowed
or interrupted (see WARNINGS). The infusion can continue at one-half the
previous rate upon improvement of patient symptoms.

Subsequent Infusions: Subsequent RITUXAN infusions can be administered at an
initial rate of 100 mg/hr, and increased by 100 mg/hr increments at
30-minute intervals, to a maximum of 400 mg/hr as tolerated.

Stability and Storage: RITUXAN vials are stable at 2-8°C (36-46°F). Do not
use beyond expiration date stamped on carton. RITUXAN vials should be
protected from direct sunlight.




HOW SUPPLIED
RITUXAN® (Rituximab) is supplied as 100 mg and 500 mg of sterile,
preservative-free, single-use vials.
Single unit 100 mg carton: Contains one 10 mL vial of RITUXAN (10 mg/mL).
NDC 50242-051-21
Single unit 500 mg carton: Contains one 50 mL vial of RITUXAN (10 mg/mL).
NDC 50242-053-06




REFERENCES
1. Valentine MA, Meier KE, Rossie S, et al. Phosphorylation of the CD20
phosphoprotein in resting B lymphocytes. J Biol Chem 1989 264(19):
11282-11287.
2. Einfeld DA, Brown JP, Valentine MA, et al. Molecular cloning of the human
B cell CD20 receptor predicts a hydrophobic protein with multiple
transmembrane domains. EMBO J 1988 7(3):711-717.

3. Anderson KC, Bates MP, Slaughenhoupt BL, et al. Expression of human B
cell-associated antigens on leukemias and lymphomas: A model of human B cell
differentiation. Blood 1984 63(6):1424-1433.

4. Tedder TF, Boyd AW, Freedman AS, et al. The B cell surface molecule B1 is
functionally linked with B cell activation and differentiation. J Immunol
1985 135(2):973-979.

5. Tedder TF, Zhou LJ, Bell PD, et al. The CD20 surface molecule of B
lymphocytes functions as a calcium channel. J Cell Biochem 1990 14D:195.

6. Press OW, Applebaum F, Ledbetter JA, Martin PJ, Zarling J, Kidd P, et al.
Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B-cell lymphomas.
Blood 1987 69(2):584-591.

7. Reff ME, Carner C, Chambers KS, Chinn PC, Leonard JE, Raab R, et al:
Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody
to CD20. Blood 1994 83(2):435-445.

8. Demidem A, Lam T, Alas S, Hariharan K, Hanna N, and Bonavida B. Chimeric
anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell
line to cell killing by cytotoxic drugs. Cancer Biotherapy &
Radiopharmaceuticals 1997 12(3):177-186.

9. Maloney DG, Liles TM, Czerwinski C, Waldichuk J, Rosenberg J,
Grillo-López A, et al. Phase I clinical trial using escalating single-dose
infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients
with recurrent B-cell lymphoma. Blood 1994 84(8):2457-2466.

10. Maloney DG, Grillo-López AJ, Bodkin D, White CA, Liles T-M, Royston I,
et al. IDEC-C2B8: Results of a phase I multiple-dose trial in patients with
relapsed non-Hodgkin's lymphoma. J Clin Oncol 1997 15(10):3266-3274.

11. Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart
JA, et al. IDEC-C2B8 (Rituximab) Anti-CD20 monoclonal antibody therapy in
patients with relapsed low-grade non-Hodgkin's lymphoma. Blood 1997
90(6):2188-2195.



Jointly Marketed by:

IDEC Pharmaceuticals Corporation
11011 Torreyana Road
San Diego, CA 92121
 Genentech, Inc.
1 DNA Way
South San Francisco, CA 94080-4990

© 1999 IDEC Pharmaceuticals Corporation and Genentech, Inc.  4809703 (566)
Revised July 1999





© 1999 Genentech, Inc.

----- Original Message -----
From: <TCABACO@AOL.COM>
To: <mol-cancer@lists.meds.com>
Sent: Thursday, October 07, 1999 5:43 PM
Subject: [MOL] No Subject


> My father has recently been diagnosed with NHL and started rituxin
> treatments.  Can you tell me more about it?  I've had no experience with
> cancer and want to besure he's taking the right stuff!
> Thanks!
> Michael
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