Rituximab

Pregnancy Category: C

Lactation: not known if excreted in breast milk, do not nurse

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

• The most common side effect of rituximab is a constellation of symptoms (fever, rigors and chills) that occur during administration of the first dose of drug. More than 80% of patients experience these side effects, and it is severe in 4-7 out of every 10,000 patients. The side effects appear only 40% of the time with the second dose of drug and become less frequent with the last two doses.
• Other common side effects related to rituximab are:
  • Nausea
  • Hives
  • Fatigue
  • Headache
  • Itching
  • Difficulty breathing due to bronchospasm
  • A sensation of swelling of the tongue or throat
  • Runny nose
  • Vomiting
  • Decreased blood pressure
  • Flushing
  • Pain at the site of the tumor
• After rituximab is administered, large numbers of tumor cells are immediately destroyed (lysed) and eliminated from the body. In 4-5 out of every 10,000 patients the products from the dead cells cannot be eliminated quickly enough and a syndrome called tumor lysis syndrome occurs. This is characterized by a rapid decline in kidney function and a sudden accumulation or decrease in minerals such as potassium, calcium and phosphate to dangerous levels. Tumor lysis syndrome occurs when the size of the tumor or the number of tumor cells circulating in the blood is large, usually within 12-24 hours after the first dose of rituximab.
• Irregular heart rhythms and infection are two other rarely-occurring side effects that may be severe. The irregular heart rhythm usually begins soon after the administration of the drug, while infection may develop from 30 days to 11 months after the end of therapy. Severe decreases in red or white blood cells and platelets (thrombocytopenia) may occur rarely with rituximab therapy. Rituximab suppresses the immune system. Therefore, serious fungal, bacterial, and new or reactivated viral infections (for example, hepatitis B or C, shingles) can occur during or after treatment with rituximab. Generally, rituximab is avoided in the presence of active, significant infections. Rituximab may also cause severe skin reactions within 1 to 13 weeks after treatment is started. Rituximab therapy is not recommended if there is an allergy to mice or rats since rituximab is made in mice or rats and may contain minute amounts of rat or mice proteins that can lead to severe allergic reactions.

Rituximab is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Rituximab is used to treat non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Rituximab is also used in combination with another drug called methotrexate to treat symptoms of adult rheumatoid arthritis.

Rituximab is also used in combination with steroid medicines to treat certain rare disorders that cause inflammation of blood vessels and other tissues in the body.

Rituximab may also be used for purposes not listed in this medication guide.

Rituximab is a prescription medication used to treat certain types of non-Hodgkin's lymphoma (a type of cancer that begins in a type of white blood cells that normally fights infection) and chronic lymphocytic leukemia (a type of cancer that begins in the white blood cells).

Rituximab is also used with another medication to treat the symptoms of rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) in people who have already been treated with a certain type of medication called a tumor necrosis factor inhibitor.

Rituximab is also used with other medications to treat granulomatosis with polyangiitis (Wegener's Granulomatosis) and microscopic polyangiitis, which are conditions in which the body attacks its own veins and other blood vessels and causes damage to organs, such as the heart and lungs.

Rituximab belongs to a group of drugs called monoclonal antibodies. These work by killing cancer cells and blocking activation of the immune system.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of rituximab include infections, diarrhea, back or joint pain, and anxiety.

Rituximab can cause dizziness and blurred vision. Do not drive or operate heavy machinery until you know how rituximab affects you.

Rituximab is part of the drug class:

• Monoclonal antibodies

Serious side effects have been reported with rituximab. See the “Rituximab Precautions” section.

Common side effects of rituximab include the following:

• diarrhea
• back or joint pain
• flushing
• night sweats
• feeling unusually anxious or worried
• runny nose

This is not a complete list of rituximab side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

WARNING: FATAL INFUSION REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Infusion Reactions

Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Monitor patients closely. Discontinue Rituxan infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion reactions.

Severe Mucocutaneous Reactions

Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan.

Hepatitis B Virus (HBV) Reactivation

HBV reactivation can occur in patients treated with Rituxan, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with Rituxan. Discontinue Rituxan and concomitant medications in the event of HBV reactivation.

Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving Rituxan.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

• Antineoplastic Agent, Anti-CD20
• Antineoplastic Agent, Monoclonal Antibody
• Antirheumatic Miscellaneous
• Immunosuppressant Agent
• Monoclonal Antibody

Note: Pretreatment with acetaminophen and an antihistamine is recommended for all indications. For oncology uses, antihyperuricemic therapy and aggressive hydration are recommended for patients at risk for tumor lysis syndrome (high tumor burden or lymphocytes >25,000/mm3). In patients with chronic lymphocytic leukemia (CLL), Pneumocystis jirovecii pneumonia (PCP) and antiherpetic viral prophylaxis is recommended during treatment (and for up to 12 months following treatment). In patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), PCP prophylaxis is recommended during and for 6 months after rituximab treatment. For patients with rheumatoid arthritis (RA), premedication with methylprednisolone 100 mg IV (or equivalent) is recommended 30 minutes prior to each dose.

Chronic lymphocytic leukemia: IV: 375 mg/m2 on the day prior to fludarabine/cyclophosphamide in cycle 1, then 500 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 (in combination with fludarabine and cyclophosphamide)

Chronic lymphocytic leukemia (off-label combinations): IV: 375 mg/m2 on the day prior to bendamustine in cycle 1, then 500 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 (in combination with bendamustine) (Eichorst 2016) or 375 mg/m2 on day 1, followed by 500 mg/m2 every 14 days for 4 doses and then 500 mg/m2 every 28 days for 3 doses (in combination with idelalisib) (Furman 2014)

Granulomatosis with polyangiitis (GPA; Wegener granulomatosis): IV: 375 mg/m2 once weekly for 4 doses (in combination with methylprednisolone IV for 1 to 3 days followed by daily prednisone)

Microscopic polyangiitis (MPA): IV: 375 mg/m2 once weekly for 4 doses (in combination with methylprednisolone IV for 1 to 3 days followed by daily prednisone)

Non-Hodgkin lymphoma (NHL; relapsed/refractory, low-grade or follicular CD20-positive, B-cell): IV: 375 mg/m2 once weekly for 4 or 8 doses (as a single agent)

Re-treatment following disease progression: 375 mg/m2 once weekly for 4 doses

For maintenance therapy (as a single agent, in patients with response to induction therapy), the following recommendations have been made: IV: 375 mg/m2 every 3 months until disease progression or maximum duration of 2 years (Rituxan IV Canadian product labeling 2016)

NHL (diffuse large B-cell): IV: 375 mg/m2 given on day 1 of each chemotherapy cycle for up to 8 doses (in combination with CHOP chemotherapy [or other anthracycline-based regimen])

NHL (follicular, CD20-positive, B-cell, previously untreated): IV: 375 mg/m2 given on day 1 of each chemotherapy cycle for up to 8 doses (in combination with first-line chemotherapy)

Maintenance therapy (as a single agent, in patients with partial or complete response to rituximab plus chemotherapy; begin 8 weeks after completion of rituximab in combination with chemotherapy): IV: 375 mg/m2 once every 8 weeks for 12 doses

NHL (nonprogressing, low-grade, CD20-positive, B-cell, after 6 to 8 cycles of first line CVP are completed): IV: 375 mg/m2 once weekly for 4 doses every 6 months for a maximum of 16 doses (as a single agent)

NHL: Combination therapy with ibritumomab: IV: 250 mg/m2 IV day 1; repeat in 7 to 9 days with ibritumomab (also see Ibritumomab monograph)

Rheumatoid arthritis: IV: 1,000 mg on days 1 and 15 (in combination with methotrexate); subsequent courses may be administered every 24 weeks (based on clinical evaluation), if necessary may be repeated no sooner than every 16 weeks

Antibody-mediated rejection in cardiac transplantation, treatment (off-label use): IV: 375 mg/m2 once weekly for 1 to 4 doses (AHA [Colvin 2015]; ISHLT [Costanzo 2010]) or 1,000 mg on days 7 and 21 or on days 7 and 22 (AHA [Colvin 2015])

Autoimmune hemolytic anemia, refractory (off-label use): IV: 375 mg/m2 once weekly for 4 doses (may continue systemic corticosteroids); a second course may be administered for relapse (Gobert 2011; Reynaud 2015; Roumier 2014)

Burkitt lymphoma (off-label use): IV: 375 mg/m2 on day 1 and 11 of cycles 1 and 3 and days 2 and 8 of cycles 2 and 4 (Thomas 2006) or 375 mg/m2 at the start of each chemotherapy cycle, followed by 2 additional doses 3 and 6 weeks after the completion of chemotherapy (Hoelzer 2014) or 50 mg/m2 on day 8 and 375 mg/m2 on days 10 and 12 of cycle 2 followed by 375 mg/m2 on day 8 of cycles 3 to 7 (Rizzieri 2014).

CNS lymphoma (off-label use): IV:

Newly diagnosed: 375 mg/m2 on day 3 every 14 days (in combination with high-dose methotrexate) until disease progression or unacceptable toxicity, or for 2 doses beyond a complete response followed by monthly treatments for up to a total of 1 year (Holdhoff 2014) or 500 mg/m2 on day 1 of each cycle for 5 to 7 induction cycles (in combination with high-dose methotrexate, vincristine, and procarbazine, followed by whole-brain radiotherapy and cytarabine consolidation) (Shah 2007)

Refractory disease: 375 mg/m2 on day 1 every 28 days (in combination with temozolomide) for 4 cycles, then followed by temozolomide monotherapy (Wong 2004)

Graft-versus-host disease (GVHD), chronic, refractory (off-label use): IV: 375 mg/m2 once weekly for 4 doses; a second course of 4 weekly doses may be administered 8 weeks after initial therapy for lack of or incomplete response (Cutler 2006) or 375 mg/m2 once weekly for 4 to 8 doses (Wolff 2011)

Hodgkin lymphoma, nodular lymphocyte-predominate, advanced (off-label use): IV: 375 mg/m2 once weekly for 4 weeks (Ekstrand 2003; Schulz 2008) or 375 mg/m2 once weekly for 4 weeks followed by maintenance dosing of 375 mg/m2 once weekly for 4 weeks every 6 months for 2 years (Advani 2014). May be administered as a single agent or in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP], or for relapsed disease, in combination with ifosfamide, carboplatin and etoposide [RICE]) (Advani 2013).

Idiopathic membranous nephropathy, resistant (off-label use): IV: 375 mg/m2 once weekly for 4 doses; repeat cycle at 6 months (Fervenza 2010) or 1,000 mg (flat dose) on days 1 and 15; may repeat cycle at 6 months (Fervenza 2008) or 375 mg/m2 once weekly for 2 doses (Dahan 2016) or 375 mg/m2 once weekly for 4 doses (Ruggenenti 2012; Ruggenenti 2015) or 375 mg/m2 as a single dose and repeated at least 1 week later only if circulating B-cells >5/mm3 were detected (Ruggenenti 2012; Ruggenenti 2015)

Immune thrombocytopenia, refractory (off-label use): IV: 375 mg/m2 once weekly for 4 doses (Arnold 2007; Godeau 2008; Provan 2010) or some patients may have a response with a dose of 100 mg (flat dose) once weekly for 4 weeks (Zaja 2010).

Lupus nephritis, refractory (off-label use): IV: 375 mg/m2 once weekly for 4 doses (Diaz-Largares 2012; Melander 2009) or 1,000 mg (flat dose) on days 0 and 15 (Diaz-Largares 2012) or 500 to 1,000 mg (flat dose) on days 1 and 15 (Vigna-Perez 2006)

Mucosa-associated lymphoid tissue lymphoma (gastric), advanced (off-label use): IV: 375 mg/m2 once weekly for 4 doses (Martinelli 2005)

Myasthenia gravis, severe, refractory (off-label use): IV: 375 mg/m2 once weekly for 4 weeks, then once a month for 2 months; repeat if symptomatic (Diaz-Manera 2012) or 375 mg/m2 once weekly for 4 weeks; may repeat if clinically indicated (Tandan 2017). Additional data may be necessary to further define the role of rituximab in the management of refractory myasthenia gravis.

Neuromyelitis optica, relapse prevention (off-label use): IV: 1,000 mg once every 2 weeks for 2 doses, repeat every 6 months or when monthly CD19 cells counts are >0.1% of total lymphocytes (Damato 2016; Mealy 2014; Trebst 2014) or 375 mg/m2 once weekly for 4 weeks, repeat every 6 months (Damato 2016; Trebst 2014). Additional data may be necessary to further define the role of rituximab in the prevention of neuromyelitis optica relapse.

Pemphigus vulgaris, newly diagnosed (off-label use): IV: 1,000 mg once every 2 weeks for 2 doses (in combination with prednisone), followed by 500 mg at months 12 and 18 (Joly 2017). Additional data may be necessary to further define the role of rituximab as initial therapy for newly diagnosed pemphigus vulgaris.

Pemphigus vulgaris, refractory (off-label use): IV: 375 mg/m2 once weekly for 4 doses (some patients also continued immunosuppressant therapy); may repeat a second time (based on response) if needed (Cholera 2016; El Tal 2006; Kasperkiewicz 2008) or 375 mg/m2 once weekly of weeks 1, 2, and 3 of a 4-week cycle, repeat for 1 additional cycle, then 1 dose per month for 4 months (total of 10 doses in 6 months), in combination with IV immune globulin (Ahmed 2006) or 1,000 mg once every 2 weeks for 2 doses (some patients also continued immunosuppressant therapy) (Cholera 2016; Kasperkiewicz 2008)

Posttransplant lymphoproliferative disorder (off-label use): IV: 375 mg/m2 once weekly for 4 doses (Choquet 2006) or 375 mg/m2 once weekly for 4 doses, followed 4 weeks later with 4 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy (Trappe 2012)

Splenic marginal zone lymphoma (off-label use): IV: 375 mg/m2 once weekly for 6 weeks followed by 375 mg/m2 once every 2 months for 1 to 2 years (Kalpadakis 2013) or 375 mg/m2 once weekly for 4 weeks as monotherapy or 375 mg/m2 on day 1 of each chemotherapy cycle for up to 6 cycles; 1 to 2 additional cycles of rituximab monotherapy may be administered for consolidation or to improve response (Else 2012). Additional data may be necessary to further define the role of rituximab in this condition.

Thrombotic thrombocytopenic purpura (acquired) (off-label use): IV: 375 mg/m2 once weekly for 4 doses (in combination with plasma exchange); up to 4 additional doses may be administered for ADAMTS13 levels remaining below normal or for persistently detectable anti-ADAMTS13 IgG antibodies (Scully 2007; Scully 2011). Rituximab should be timed to be administered immediately following plasma exchange; allow 24 hours after rituximab before the next plasma exchange (McDonald 2010; Sayani 2015).

Waldenström macroglobulinemia (off-label use): IV:

Single-agent rituximab: 375 mg/m2 once weekly for 4 weeks as a single agent; may repeat cycle one time after 12 weeks (Dimopoulos 2002).

In combination with cyclophosphamide and dexamethasone: 375 mg/m2 on day 1 every 21 days for 6 cycles (Dimopoulos 2007).

In combination with bortezomib: 375 mg/m2 on days 1, 8, 15, and 22 every 28 days during cycles 1 and 4; treatment is continued for 6 cycles, with a total of 8 rituximab doses (Ghobrial 2010).

In combination with bortezomib and dexamethasone: 375 mg/m2 on days 1, 8, 15, and 22 every 35 days during cycles 2 and 5; treatment is administered for 6 cycles, with a total of 8 rituximab doses (Dimopoulos 2013) or 375 mg/m2 on day 11 every 21 days for 4 cycles (induction); after a 12-week break, 4 additional maintenance cycles (spaced 12 weeks apart) were administered (Treon 2009).

In combination with bendamustine: 375 mg/m2 on day 1 every 28 days for 4 cycles; single rituximab doses were also administered 1 week prior to the first cycle and 4 weeks after the last cycles (for a total of 6 rituximab doses) (Rummel 2005).

In combination with carfilzomib and dexamethasone: 375 mg/m2 on days 2 and 9 every 21 days for 6 induction cycles, followed by 375 mg/m2 on day 2 every 8 weeks for 8 maintenance cycles (Treon 2014).

CBC with differential and platelets (obtain prior to treatment and at weekly to monthly intervals and more frequently in patients with lymphoid malignancies, or at 2- to 4-month intervals in rheumatoid arthritis patients, GPA and MPA), electrolytes (in patients at risk for TLS), renal function (in patients at risk for TLS), fluid/hydration status balance; blood pressure, vital signs.

Screen all patients for HBV infection prior to therapy initiation (eg, HBsAG and anti-HBc measurements). In addition, carriers and patients with evidence of current infection or recovery from prior hepatitis B infection should be monitored closely for clinical and laboratory signs of HBV reactivation and/or infection during therapy and for up to 2 years following completion of treatment. Hepatitis B virus (HBV) screening recommendations (ASCO provisional clinical opinion update [Hwang 2015]): Screen for HBV infection with hepatitis B surface antigen (HBsAG) and hepatitis B core antibody (anti-HBc) tests prior to treatment initiation; either a total anti-HBc (with both IgG and IgM) or anti-HBc IgG test should be used to screen for chronic or resolved HBV infection (do not use anti-HBc IgM as it may only confirm acute HBV infection). HBsAg negative/anti-HBc positive patients should be monitored for HBV reactivation with HBV DNA and ALT testing approximately every 3 months during treatment.

Monitor for infusion reactions; signs of active hepatitis B infection (during and for up to 12 months after therapy completion); cardiac monitoring during and after infusion (in rheumatoid arthritis patients and in patients with pre-existing cardiac disease or if arrhythmias develop during or after subsequent infusions); monitor for signs/symptoms of bowel obstruction/perforation (abdominal pain, vomiting); signs or symptoms of progressive multifocal leukoencephalopathy (focal neurologic deficits, which may present as hemiparesis, visual field deficits, cognitive impairment, aphasia, ataxia, and/or cranial nerve deficits); if PML is suspected, obtain brain MRI scan and lumbar puncture; signs/symptoms of TLS and/or mucocutaneous skin reactions.

Information for all healthcare professionals administering this drug: Administer this drug only as an IV infusion. Do not administer as an IV push or bolus. Premedicate before each infusion with acetaminophen and an antihistamine.

FIRST INFUSION: Initiate infusion at a rate of 50 mg/hr; in the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr

SUBSEQUENT INFUSIONS:
STANDARD INFUSION: Initiate infusion at a rate of 100 mg/hr; in the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr
FOR PREVIOUSLY UNTREATED FOLLICULAR NON-HODGKIN'S LYMPHOMA (NHL) AND DIFFUSE LARGE B-CELL NHL (DLBCL) PATIENTS: If patients did not experience a Grade 3 or 4 infusion related adverse event during Cycle 1, a 90 minute infusion can be administered in Cycle 2 with a glucocorticoid-containing chemotherapy regimen:
-Initiate infusion at a rate of 20% of the total dose given in the first 30 minutes and administer the remaining 80% of the total dose over the next 60 minutes. If the 90 minute infusion is tolerated in Cycle 2, the same rate can be used for subsequent cycles.
-Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count greater than or equal to 5000/mm3 before Cycle 2 should not be given the 90 minute infusion.
-Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

RECOMMENDED DOSE FOR NON-HODGKIN'S LYMPHOMA (NHL):
Recommended dose: 375 mg/m2 IV according to the following schedules:
-Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL: 375 mg/m2 IV once weekly for 4 or 8 doses
-Retreatment for Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL: 375 mg/m2 IV once weekly for 4 doses
-Previously Untreated, Follicular, CD20-Positive, B-Cell NHL: 375 mg/m2 IV, administered on Day 1 of each cycle of chemotherapy, for up to 8 doses. In patients with complete or partial response, initiate rituximab maintenance 8 weeks following completion of rituximab in combination with chemotherapy. Administer rituximab as a single agent every 8 weeks for 12 doses
-Non-progressing, Low-grade, CD20-positive, B-cell NHL, after first-line CVP chemotherapy: Following completion of 6 to 8 cycles of CVP chemotherapy, administer 375 mg/m2 IV once weekly for 4 doses at 6 month intervals to a maximum of 16 doses
-Diffuse Large B-Cell NHL: 375 mg/m2 on Day 1 of each cycle of chemotherapy for up to 8 infusions

RECOMMENDED DOSE AS A COMPONENT OF IBRITUMOMAB TIUXETAN THERAPY FOR TREATMENT OF NHL:
-Rituximab 250 mg/m2 should be infused within 4 hours prior to the administration of Indium-111- (In-111-) ibritumomab tiuxetan and within 4 hours prior to the administration of Yttrium-90- (Y-90-) ibritumomab tiuxetan.
-Administration of rituximab and In-111-ibritumomab tiuxetan should precede rituximab and Y-90-ibritumomab tiuxetan by 7 to 9 days.
-Refer to the ibritumomab tiuxetan package insert for full prescribing information regarding the ibritumomab tiuxetan therapeutic regimen.

Use: Non-Hodgkin's Lymphoma (NHL):
-Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
-Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to this drug in combination with chemotherapy, as single-agent maintenance therapy
-Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line CVP chemotherapy
-Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

Information for all healthcare professionals administering this drug: Administer this drug only as an IV infusion. Do not administer as an IV push or bolus. Premedicate before each infusion with acetaminophen and an antihistamine. Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

-FIRST INFUSION: Initiate infusion at a rate of 50 mg/hr; in the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr
-SUBSEQUENT INFUSIONS: Initiate infusion at a rate of 100 mg/hr; in the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr
-Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

RECOMMENDED DOSE FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): 375 mg/m2 IV the day prior to the initiation of FC chemotherapy, then 500 mg/m2 on Day 1 of cycles 2 through 6 (every 28 days)

Use: This drug is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL

Administration advice:
-Do not administer as an intravenous push or bolus. Administer only as an IV infusion.

General:
-Extreme caution and careful monitoring are recommended in patients who have a high number of circulating malignant cells (greater than 25 x 10(9)/L). These patients may have an increased risk of severe infusion-related reactions, which can have a fatal outcome. This is particularly applicable to patients with a high tumor burden, such as chronic lymphocytic leukemia or mantle cell lymphoma. A reduced infusion rate should be considered for the first infusion in these patients.
-Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion.
-Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.
-Since transient hypotension may occur during the infusion, consideration should be given to withholding antihypertensive medications 12 hours prior to the infusion.

Storage requirements:
-Consult the manufacturer product information.

Reconstitution/preparation techniques:
-Consult the manufacturer product information.

IV compatibility:
-Consult the manufacturer product information.

Laboratory Monitoring:
-Because this drug targets all CD20-positive B lymphocytes, malignant and nonmalignant, complete blood counts (CBC) and platelet counts should be obtained at regular intervals during therapy and more frequently in patients who develop cytopenias. The duration of cytopenias caused by this drug can extend well beyond the treatment period.