Usual Adult Dose for non-Hodgkin's Lymphoma

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

NON-HODGKIN'S LYMPHOMA (NHL):
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 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 this drug 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 IV on Day 1 of each cycle of chemotherapy for up to 8 infusions.

AS A COMPONENT OF IBRITUMOMAB TIUXETAN THERAPY FOR NHL:

• Infuse rituximab 250 mg/m2 IV in accordance with the ibritumomab tiuxetan package insert.
• Refer to the ibritumomab tiuxetan package insert for full prescribing information.

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.

Comments:

• Premedicate before each infusion with acetaminophen and an antihistamine.
• For patients administered the 90-minute infusion rate, the glucocorticoid component should be administered prior to each infusion.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.

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

Usual Adult Dose for Lymphoma

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

NON-HODGKIN'S LYMPHOMA (NHL):
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 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 this drug 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 IV on Day 1 of each cycle of chemotherapy for up to 8 infusions.

AS A COMPONENT OF IBRITUMOMAB TIUXETAN THERAPY FOR NHL:

• Infuse rituximab 250 mg/m2 IV in accordance with the ibritumomab tiuxetan package insert.
• Refer to the ibritumomab tiuxetan package insert for full prescribing information.

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.

Comments:

• Premedicate before each infusion with acetaminophen and an antihistamine.
• For patients administered the 90-minute infusion rate, the glucocorticoid component should be administered prior to each infusion.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.

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

Usual Adult Dose for Rheumatoid Arthritis

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

Rituximab:

• Administer as two 1000 mg IV infusions separated by 2 weeks.
• Glucocorticoids administered as methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions.
• Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks.
• Rituximab is given in combination with methotrexate.

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.

Comments:

• 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.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.

Use: In combination with methotrexate for the treatment of adult patients with moderately- to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies

Usual Adult Dose for Chronic Lymphocytic Leukemia

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

375 mg/m2 IV the day prior to the initiation of FC chemotherapy, then 500 mg/m2 IV on Day 1 of cycles 2 through 6 (every 28 days)

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

Comments:

• Premedicate before each infusion with acetaminophen and an antihistamine.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.
• Provide prophylaxis treatment for Pneumocystis jirovecii pneumonia (PCP) and herpes virus infections for patients with CLL during treatment and for up to 12 months following treatment.

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

Usual Adult Dose for Wegener's Granulomatosis

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

Induction Treatment of Patients with Active GPA/MPA: 375 mg/m2 IV once weekly for 4 weeks

• Glucocorticoids administered as methylprednisolone 1000 mg IV per day for 1 to 3 days followed by oral prednisone per clinical practice. This regimen should begin within 14 days prior to or with the initiation of rituximab and may continue during and after the 4-week course of rituximab.
• Methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion.

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

Follow up Treatment of Patients with GPA/MPA who have achieved disease control with induction treatment: Administer as two 500 mg IV infusions separated by 2 weeks, followed by 500 mg IV infusion every 6 months thereafter based on clinical evaluation.

• If induction treatment of active disease was with this drug, follow up treatment with this drug should be initiated within 24 weeks after the last induction infusion or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion.
• If induction treatment of active disease was with other standard of care immunosuppressants, follow up treatment with this drug should be initiated within the 4-week period that follows disease control.

Comments:

• Premedicate before each infusion with acetaminophen and an antihistamine.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.
• Provide prophylaxis treatment for Pneumocystis jirovecii pneumonia (PCP) for patients with GPA and MPA during treatment and for up to 6 months following treatment.

Uses: In combination with glucocorticoids for Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)

Usual Adult Dose for Microscopic Polyangiitis

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

Induction Treatment of Patients with Active GPA/MPA: 375 mg/m2 IV once weekly for 4 weeks

• Glucocorticoids administered as methylprednisolone 1000 mg IV per day for 1 to 3 days followed by oral prednisone per clinical practice. This regimen should begin within 14 days prior to or with the initiation of rituximab and may continue during and after the 4-week course of rituximab.
• Methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion.

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

Follow up Treatment of Patients with GPA/MPA who have achieved disease control with induction treatment: Administer as two 500 mg IV infusions separated by 2 weeks, followed by 500 mg IV infusion every 6 months thereafter based on clinical evaluation.

• If induction treatment of active disease was with this drug, follow up treatment with this drug should be initiated within 24 weeks after the last induction infusion or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion.
• If induction treatment of active disease was with other standard of care immunosuppressants, follow up treatment with this drug should be initiated within the 4-week period that follows disease control.

Comments:

• Premedicate before each infusion with acetaminophen and an antihistamine.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.
• Provide prophylaxis treatment for Pneumocystis jirovecii pneumonia (PCP) for patients with GPA and MPA during treatment and for up to 6 months following treatment.

Uses: In combination with glucocorticoids for Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)

Usual Adult Dose for Pemphigus

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

Initial dose: Administer two 1000 mg IV infusions separated by 2 weeks in combination with a tapering course of glucocorticoids
Maintenance dose: 500 mg IV at Month 12 and every 6 months thereafter or based on clinical evaluation
Treatment of relapse: 1000 mg IV on relapse and consider resuming or increasing the glucocorticoid dose based on clinical evaluation

• Subsequent infusions of this drug may be administered no sooner than 16 weeks following the previous infusion.

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

Comments:

• Premedicate before each infusion with acetaminophen and an antihistamine.
• Prior to the first infusion screen patients for HBV infection by measuring HBsAg and anti-HBc.
• Obtain complete blood counts including platelets (CBC) prior to the first dose.
• Consider prophylaxis treatment for Pneumocystis jirovecii pneumonia (PCP) for patients with PV during and following treatment with this drug.

Use: For moderate to severe pemphigus vulgaris (PV)

Usual Pediatric Dose for Wegener's Granulomatosis

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

2 years and older:
INDUCTION TREATMENT FOR ACTIVE GPA/MPA:

• Administer 375 mg/m2 IV once a week for 4 weeks
• Prior to the first infusion, administer methylprednisolone 30 mg/kg (not to exceed 1 g/day) IV once a day for 3 day.
• Following IV methylprednisolone administration, oral steroids should be continued per clinical practice.

FOLLOW UP TREATMENT OF PATIENTS WITH GPA/MPA WHO HAVE ACHIEVED DISEASE CONTROL WITH INDUCTION TREATMENT:

• Administer as two 250 mg/m2 IV infusions separated by 2 weeks, followed by 250 mg/m2 IV infusion every 6 months thereafter based on clinical evaluation.
• If induction treatment of active disease was with rituximab, initiate follow up treatment within 24 weeks after the last induction infusion product or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion.
• If induction treatment of active disease was with other standard of care immunosuppressants, initiate rituximab follow-up treatment within the 4-week period following disease control.

Use: This drug, in combination with glucocorticoids, is indicated for the treatment of pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)

Usual Pediatric Dose for Microscopic Polyangiitis

NOTE: Not all products are approved for the same indications or patient age populations. Refer to the manufacturer product information for indications.

2 years and older:
INDUCTION TREATMENT FOR ACTIVE GPA/MPA:

• Administer 375 mg/m2 IV once a week for 4 weeks
• Prior to the first infusion, administer methylprednisolone 30 mg/kg (not to exceed 1 g/day) IV once a day for 3 day.
• Following IV methylprednisolone administration, oral steroids should be continued per clinical practice.

FOLLOW UP TREATMENT OF PATIENTS WITH GPA/MPA WHO HAVE ACHIEVED DISEASE CONTROL WITH INDUCTION TREATMENT:

• Administer as two 250 mg/m2 IV infusions separated by 2 weeks, followed by 250 mg/m2 IV infusion every 6 months thereafter based on clinical evaluation.
• If induction treatment of active disease was with rituximab, initiate follow up treatment within 24 weeks after the last induction infusion product or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion.
• If induction treatment of active disease was with other standard of care immunosuppressants, initiate rituximab follow-up treatment within the 4-week period following disease control.

Use: This drug, in combination with glucocorticoids, is indicated for the treatment of pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

US BOXED WARNINGS:
FATAL INFUSION REACTIONS/SEVERE MUCOCUTANEOUS REACTIONS/HEPATITIS B VIRUS REACTIVATION/PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY:

• INFUSION REACTIONS: This drug can cause serious, including fatal, infusion reactions. Deaths within 24 hours of infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Patients should be monitored closely. Discontinue the 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 this drug.
• HEPATITIS B VIRUS (HBV) REACTIVATION: HBV reactivation can occur, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before therapy initiation and monitor patients during and after the infusion. Discontinue this drug and concomitant medications for HBV reactivation.
• PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): PML, including fatal cases, can occur in patients receiving this drug.

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 2 years for the treatment of GPA and MPA; safety and efficacy have not been established in patients younger than 18 years for all other indications.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Do not administer the IV formulation as an IV push or bolus.

General:

• Monitoring is 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 be fatal. 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.
• It is important to check the medicinal product labels to ensure that the appropriate formulation (IV or subcutaneous formulation) is being given to the patient, as prescribed.
• The subcutaneous formulation is not intended for IV administration and should be given via subcutaneous injection only.

Storage requirements:

• IV FORMULATION: Store vials refrigerated at 2C to 8C (36F to 46F). Protect from direct sunlight. Do not freeze or shake.
• SUBCUTANEOUS FORMULATION: Store unopened vial in a refrigerator (2C to 8C). Protect from direct sunlight. Once transferred from the vial into the syringe, the subcutaneous formulation is physically and chemically stable for 48 hours at 2C to 8C and subsequently for 8 hours at 30C in diffuse daylight.

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.

Frequently asked questions

• What are the new drugs for the treatment of rheumatoid arthritis (RA)?
• How many biosimilars have been approved in the United States?
• Is Truxima a chemotherapy drug?
• What is the success rate of Rituxan (rituximab) in patients with blood cancers?
• What is the difference between Truxima and Rituxan?
• What causes infusion reactions to rituximab?
• What is the success rate of Rituxan (rituximab) in rheumatoid arthritis?
• Are lung nodules common after Bendeka & Rituxan therapy?
• What is the difference between Rituxan and Rituxan Hycela?