Dosing and uses of Rituxan (rituximab)
Adult dosage forms and strengths
injectable solution
- 10mg/mL
Non-Hodgkin Lymphoma
Indications
- 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 rituximab in combination with chemotherapy, as single-agent maintenance therapy
- Nonprogressing (including stable disease), low-grad, 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
Recommended dose for NHL
- 375 mg/m² IV infusion according to the following schedules
- Relapsed or refractory low-grade or follicular, CD20-positive, B-cell NHL: Once weekly x4-8 doses
- Retreatment for relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL: Once weekly x4 doses
- Previously untreated, follicular, CD20-positive, B-cell NHL: Administer on Day 1 of each chemotherapy cycle for up to 8 doses; with complete or partial response, initiate maintenance 8 weeks following completion of combination chemotherapy as a single-agent q8weeks for 12 doses
- Nonprogressing, low-grade, CD20-positive, B-cell NHL, after first-line CVP chemotherapy: Following completion of 6-8 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses
- Diffuse large B-cell NHL: Administer on Day 1 of each cycle of chemotherapy for up to 8 infusions
Chronic Lymphocytic Leukemia
Indicated for untreated and previously treated CD20-positive CLL; combined therapy with fludarabine and cyclophosphamide (FC)
375 mg/m² IV infusion on day 1 of 1st cycle (for 1st cycle, administer 1 day before chemotherapy with FC), THEn
500 mg/m² IV on day 1 of subsequent cycles (administer on same day as chemotherapy with FC)
Repeat q28 days x6 cycles
Fludarabine & cyclophosphamide dosage
- Fludarabine: 25 mg/m² IV qDay x 3 days
- Cyclophosphamide: 250 mg/m² IV qDay x3 days
- Repeat q28 days x 6 cycles
Rheumatoid Arthritis
1000 mg IV infusion, repeat after 2 week (2 infusions separated by 2 week is 1 course)
Repeat course q24weeks or based on clinical evaluation (but no sooner than 16 weeks)
Used in combo with methotrexate
Premedicate with glucocorticoids 30 minutes before infusion to reduce infusion rxn
Not to exceed 1000 mg/dose
Wegener Granulomatosis
375 mg/m² IV qWeek x4 weeks
Administration
- Premedicate with acetaminophen and antihistamine before rituximab infusion
- Administer methylprednisolone 1 g IV/day x1-3 days, then prednisone 1 mg/kg/day PO; not to exceed 80 mg/day and taper as clinically needed
- Initiate glucocorticoids within 14 days prior to or with initiation or rituximab; may continue during and after the 4-week rituximab treatment course
- Concomitant use of immunosuppressants other than corticosteroids has not been studied in Wegener granulomatosis
- Safety and efficacy of subsequent courses of rituximab not established
Microscopic Polyangiitis
375 mg/m² IV qWeek x4 weeks
Administration
- Premedicate with acetaminophen and antihistamine before rituximab infusion
- Administer methylprednisolone 1 g IV/day x1-3 days, then prednisone 1 mg/kg/day PO; not to exceed 80 mg/day and taper as clinically needed
- Initiate glucocorticoids within 14 days prior to or with initiation or rituximab; may continue during and after the 4-week rituximab treatment course
- Concomitant use of immunosuppressants other than corticosteroids has not been studied in microscopic polyangiitis
- Safety and efficacy of subsequent courses of rituximab not established
Orphan Designations
Treatment of immune thrombocytopenic purpura (ITP)
Treatment of pemphigus vulgaris
Sponsor
- Genentech, Inc; 1 DNA Way; South San Francisco, CA 94080-4990
Pediatric dosage forms and strengths
Safety and efficacy not established
Rheumatoid Arthritis: Safety and effectiveness not established; FDA has not required pediatric studies in polyarticular juvenile idiopathic arthritis (PJIA) patients <16 years due to concerns regarding the potential for prolonged immunosuppression as a result of B-cell depletion in the developing juvenile immune system
Wegener Granulomatosis: Safety and effectiveness not established
Rituxan (rituximab) adverse (side) effects
>10%
NHL
- Angioedema (11%), hypotension (10%)
- Asthenia (26%), chills (33%), dizziness (10%), fever (53%), headache (19%)
- Pruritus (14%), rash (15%)
- Abdominal pain (14%), diarrhea (10%), nausea (23%), vomiting (10%)
- Leukopenia (14%), lymphopenia (48%), neutropenia (14%), thrombocytopenia (12%)
- Back pain (10%), myalgia (10%)
- Cough (13%), rhinitis (12%)
- Infection (31%), night sweats (15%)
1-10%
NHL
- Edema
- Flushing
- Hypertension
- Anxiety
- Anemia
- Elevated LDH
- Hyperglycemia
- Bronchospasm, dyspnea, sinusitis, throat irritation, urticaria
RA (Rituximab+Methotrexate vs Methotrexate Alone)
- Hypertension
- Anxiety, asthenia, chills, migraine, paresthesia, pyrexia
- Pruritus, urticaria
- Dyspepsia, nausea, upper abd pain
- Hypercholesterolemia
- Arthralgia
- Rhinitis, throat irritation, URI
Frequency not defined
Tumor lysis syndrome
Lymphoid malignancies
Hypogammaglobulinemia
Postmarketing Reports
Grade 3-4 prolonged or late-onset neutropenia
Warnings
Black box warnings
Fatal infusion reaction
- Can result in serious, including fatal reactions
- Deaths within 24 hours of infusion have occurred
- Approximately 80% of fatal infusion reactions occurred in association with the first infusion
- Carefully monitor patients during infusion
- Discontinue infusion and provide medical treatment for grade 3 or 4 reactions
Mucocutaneous reactions (severe)
- Severe, including fatal, mucocutaneous reactions reported including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis
Progressive multifocal leukoencephalopathy
- John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy and death has been reported in patients treated with rituximab
Reactivation of hepatitis B
- Reactivation of hepatitis B virus (HBV) infection reported, including deaths
- Screen all patients for HBV infection before initiating drug by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc)
- Consult with hepatitis experts regarding monitoring and use of HBV antiviral therapy when screening identifies patients at risk of HBV reactivation due to evidence of prior HBV infection
- Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis B or HBV reactivation during therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy
- In patients who develop reactivation of HBV, immediately discontinue the drug and start appropriate HBV treatment, also discontinue any chemotherapy until the HBV infection is controlled or resolved
- Because of insufficient data, no recommendation can be made regarding the resumption of the drug in patients who develop HBV reactivation hepatitis
Contraindications
Hypersensitivity to any component, murine proteins
Cautions
Cardiac arrhythmia, angina, high tumor burden, concomitant cisplatin
Infusion reactions may occur and are potentially fatal; reactions may resolve with slowing or suspending infusion; risk diminishes with subsequent infusions
Risk of potentially fatal mucocutaneous reactions
Risk of potentially fatal tumor lysis syndrome
Increased risk of potentially fatal hepatitis B virus reactivation
Potential risk of progressive multifocal leukoencephalopathy
Pregnancy and lactation
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.
Pharmacology of Rituxan (rituximab)
Mechanism of action
Humanized monoclonal antibody, binds to CD20 antigen, inducing complement- or antibody-mediated cytolysis
Elimination
Half-life: 59.8 hr (1st dose); 174 hr (4th dose)
Administration
IV Preparation
Reconstitution: withdraw necessary amount of rituximab and dilute to a final concentration of 1-4 mg/mL into an infusion bag containing either NS or D5W
IV Administration
Consider premedication (ie, acetaminophen and diphenhydramine, or glucocorticoids for RA) before each infusion
Premedication with diphenhydramine or acetaminophen may attenuate infusion-related events
Because transient hypotension may occur during infusion, consider withholding antihypertensive medications 12 hr prior to infusion
Administer by slow IV infusion only; do not administer as an IV
First IV infusion rate: Start 50 mg/hr; increase by 50 mg/hr q30min, not to exceed 400 mg/hr
Drug is associated with hypersensitivity reactions which may respond to adjustments in infusion rate
Subsequent IV infusions (90 minutes)
- Standard IV infusions: Start 100 mg/hr, increase by 100 mg/hr q30min, not to exceed 400 mg/hr; institutional protocols may allow faster increments
- Previously untreated patients with follicular NHL or diffuse large B-cell lymphoma: 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 at a rate of 20% of the total dose given in the first 30 minutes and the remaining 80% of the total dose given over the next 60 minutes
- If tolerated in Cycle 2, the same rate can be used when administering the remainder of the treatment regimen (through Cycle 6 or 8)
- Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count ≥5000/mm³ before Cycle 2 should not be administered the 90-minute infusion
Infusion-related adverse effects
- Hypotension, bronchospasm, and angioedema have occurred as part of an infusion-related symptom complex
- Interrupt infusion for severe reactions and resume at a 50% reduction in rate (eg, from 100 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
- Discontinue infusions if serious or life-threatening cardiac arrhythmias
Storage
Store under refrigeration
Protect vials from direct sunlight
Solutions for infusion are stable at 2-8°C (36-46°F) for 24 hr
