rituximab

High Alert

Riabni, Rituxan, Ruxience, and Truxima

Treatment of the following conditions:
- Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) (as monotherapy).
- 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.
- Non-progressing, low-grade, CD20-positive, B-cell NHL following treatment with cyclophosphamide, vincristine, and prednisone (as monotherapy).
- Previously untreated diffuse large B-cell, CD20-positive, NHL (in combination with CHOP or another anthracycline-based chemotherapy regimen).
- CD-20 positive chronic lymphocytic leukemia (CLL) (in combination with fludarabine and cyclophosphamide).
- Moderately to severely active rheumatoid arthritis in patients who have had an inadequate response to ≥1 TNF antagonist therapies (with methotrexate).
- Granulomatosis with polyangiitis (Wegener's granulomatosis) and microscopic polyangiitis (in combination with glucocorticoids).

Rituxan only

Treatment of the following condition:
- Moderate to severe pemphigus vulgaris.
Previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia (in combination with chemotherapy).

Action ⬆ ⬇

Binds to the CD20 antigen on the surface of lymphoma cells, preventing the activation process for cell cycle initiation and differentiation.

Therapeutic effects:

Death of lymphoma cells.
Prolonged progression-free survival in CLL.
Reduced signs and symptoms of rheumatoid arthritis.
Achievement of complete remission in granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Binds specifically to CD20 binding sites on lymphoma cells.

Metabolism/Excretion: Unknown.

Half-Life: 59.8–174 hr (depending on tumor burden).

Time/Action Profile ⬆ ⬇

(B-cell depletion)

ROUTE	ONSET	PEAK	DURATION
IV	within 14 days	3–4 wk	6–9 mo‡

‡Duration of depletion after 4 wk of treatment.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to murine (mouse) proteins;
OB: Can pass placental barrier potentially causing fetal B-cell depletion. Use during pregnancy only if clearly needed;
Lactation: Lactation.

Use Cautiously in:

Pre-existing bone marrow depression;
Hepatitis B virus (HBV) infection (may reactivate infection during and for several mo after treatment);
Systemic lupus erythematosus (may cause fatal progressive multifocal leukoencephalopathy [PML]);
HIV infection (may ↑ risk of HIV-associated lymphoma);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established for children 6 mo (mature B-cell lymphomas and B-cell acute leukemia), 2 yr (granulomatosis with polyangiitis and microscopic polyangiitis), and 18 yr (all other indications).

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, ARRHYTHMIAS, peripheral edema

Derm: flushing, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria

Endo: hyperglycemia

F and E: hypocalcemia

GI: abdominal pain, altered taste, dyspepsia, HBV REACTIVATION

GU: renal failure

Hemat: ANEMIA, NEUTROPENIA, THROMBOCYTOPENIA

MS: arthralgia, back pain

Neuro: headache, PML

Resp: bronchospasm, cough, dyspnea

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), infection, INFUSION REACTIONS, TUMOR LYSIS SYNDROME

Interactions ⬆ ⬇

Drug-drug:

May ↓ antibody response to or ↑ risk of adverse reactions to live vaccines; avoid use during treatment; inactive vaccines should be administered ≥4 wk prior to start of therapy.

Route/Dosage ⬆ ⬇

Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell Non-Hodgkin’s Lymphoma

IV (Adults ): 375 mg/m² once weekly for 4 or 8 doses; may retreat with 375 mg/m² once weekly for 4 doses.

Previously Untreated Follicular, CD20–Positive, B-Cell Non-Hodgkin’s Lymphoma

IV (Adults ): 375 mg/m² given on Day 1 of each cycle of chemotherapy with cyclophosphamide, vincristine, and prednisone for up to 8 doses; if patients experience complete or partial response, give 375 mg/m² (as monotherapy) every 8 wk for 12 doses (initiate this maintenance therapy 8 wk after completion of rituximab + cyclophosphamide/vincristine/prednisone regimen).

Non-Progressing Low-Grade, CD20–Positive, B-Cell Non-Hodgkin’s Lymphoma

IV (Adults ): For patients who have not progressed following 6–8 cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone, 375 mg/m² given once weekly for 4 doses given every 6 mo for up to 16 doses.

Diffuse Large B-Cell Non-Hodgkin’s Lymphoma

IV (Adults ): 375 mg/m² given on Day 1 of each cycle of chemotherapy for up to 8 infusions.

Previously Untreated Mature B-Cell Lymphomas and B-Cell Acute Leukemia

IV (Children ≥6 mo): 375 mg/m²/dose in combination with systemic Lymphome Malin B chemotherapy regimen; administer 2 doses during each of the two induction courses (Day −2 and Day 1), and one dose during each of the two consolidation cycles (Day 1) (6 doses total)

Chronic Lymphocytic Leukemia

IV (Adults ): 375 mg/m² given on the day before initiating chemotherapy with fludarabine and cyclophosphamide, then 500 mg/m² on Day 1 of cycles 2–6 (every 28 days).

Rheumatoid Arthritis

IV (Adults ): 1000 mg every 2 wk for 2 doses; subsequent courses should be administered every 24 wk (not sooner than every 16 wk).

Granulomatosis With Polyangiitis and Microscopic Polyangiitis

IV (Adults ): Induction treatment: 375 mg/m² once weekly for 4 wk; Follow-up treatment in patients who have achieved disease control with induction treatment: 500 mg every 2 wk for 2 doses (should be started 16–24 wk after last rituximab induction dose; if achieved disease control with another agent, start follow-up treatment within 4 wk after last induction dose of that agent), then 500 mg every 6 mo thereafter.
IV (Children ≥2 yr): Induction treatment: 375 mg/m² once weekly for 4 wk; Follow-up treatment in patients who have achieved disease control with induction treatment: 250 mg/m² every 2 wk for 2 doses (should be started 16–24 wk after last rituximab induction dose; if achieved disease control with another agent, start follow-up treatment within 4 wk after last induction dose of that agent), then 250 mg/m² every 6 mo thereafter.

Pemphigus Vulgaris

IV (Adults ): 1000 mg every 2 wk for 2 doses, then maintenance dose of 500 mg infusion at month 12 and then every 6 mo thereafter. Upon relapse, administer 1000 mg.

Availability ⬆ ⬇

Solution for injection: 10 mg/mL

Assessment ⬆ ⬇

Monitor patient for fever, chills/rigors, nausea, urticaria, fatigue, headache, pruritus, bronchospasm, dyspnea, sensation of tongue or throat swelling, rhinitis, vomiting, hypotension, flushing, and pain at disease sites. Infusion-related events occur frequently within 30 min–2 hr of beginning 1st infusion and may resolve with slowing or discontinuing infusion and treatment with IV saline, diphenhydramine, and acetaminophen. Patients with increased risk (females, patients with pulmonary infiltrates, chronic lymphocytic leukemia, or mantle cell leukemia) may have more severe reactions, which may be fatal. Signs of severe reactions include hypotension, angioedema, hypoxia, or bronchospasm and may require interruption of infusion. May result in pulmonary infiltrates, adult respiratory distress syndrome, MI, ventricular fibrillation, and cardiogenic shock. Monitor closely. Incidence decreases with subsequent infusions.
Monitor patient for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia) usually occurring 12–24 hr after 1st infusion. Risks are higher in patients with greater tumor burden; may be fatal. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
Assess for signs and symptoms of hypersensitivity reactions (hypotension, bronchospasm, angioedema) during administration. May respond to decrease in infusion rate. Premedication with diphenhydramine and acetaminophen is recommended. Treatment includes diphenhydramine, acetaminophen, bronchodilators, or IV saline as indicated. Epinephrine, antihistamines, and corticosteroids should be readily available in the event of a severe reaction. If severe reactions occur, discontinue infusion; may be resumed at 50% of the rate when symptoms have resolved completely.
Monitor ECG during and immediately after infusion in patients with pre-existing cardiac conditions (arrhythmias, angina) or patients who have developed arrhythmias during previous infusions of rituximab. Life-threatening arrhythmias may occur.
Assess for signs of PML (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) periodically during therapy.
Assess for infection during and for 1 yr after therapy. Bacterial, fungal, and new or reactivated viral infections may occur. Screen patient for HBV infection prior to therapy. Discontinue rituximab and any concomitant chemotherapy in patients who develop viral hepatitis or other serious infections, and institute appropriate treatment.
Assess for mucocutaneous reactions periodically during therapy. May cause SJS and TEN. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.

Lab Test Considerations:

Verify negative pregnancy status before starting therapy.Monitor CBC and platelet count before starting and regularly during therapy and frequently in patients with blood dyscrasias. May cause anemia, thrombocytopenia, or neutropenia.
- Frequently causes B-cell depletion with an associated ↓ in serum immunoglobulins in a minority of patients; does not appear to cause an increased incidence of infection.
- Obtain HBsAg and anti-HBc to screen patient for HBV infection before initiating therapy. May cause reactivation of HBV up to 24 mo after therapy.

Implementation ⬆ ⬇

Do not confuse rituximab with infliximab. Do not confuse Rituxan with Rituxan Hycela.
Transient hypotension may occur during infusion; antihypertensive medications may be held for 12 hr before infusion.
Rheumatoid Arthritis: Administer 100 mg methylprednisolone IV or equivalent 30 min prior to each infusion to minimize infusion reactions.
Granulomatosis With Polyangiitis and Microscopic Polyangiitis: Administer methylprednisolone 1000 mg IV per day for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) to treat severe vasculitis symptoms. Begin regimen within 14 days prior to or with the initiation of rituximab and may continue during and after the 4-wk course of rituximab treatment.
Prophylaxis against Pneumocystis jiroveci pneumonia and herpes virus recommended during treatment and for up to 12 mo following treatment as appropriate for patients with CLL, and during and for at least 6 mo following last rituximab infusion for patients with granulomatosis with polyangiitis and microscopic polyangiitis.

IV Administration:

Intermittent Infusion: Diluent: Dilute with 0.9% NaCl or D5W.Concentration: 1–4 mg/mL. Gently invert bag to mix. Solution is clear to slightly opalescent and colorless to slightly yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Discard unused portion remaining in vial. Solution is stable for 12 hr at room temperature and for 24 hr if refrigerated.
Rate: Do not administer as an IV push or bolus.
- First infusion: Administer at an initial rate of 50 mg/hr. If hypersensitivity or infusion-related events do not occur, rate may be escalated in 50-mg/hr increments every 30 min to a maximum of 400 mg/hr.
- Subsequent infusions: May be administered at an initial rate of 100 mg/hr and increased by 100-mg/hr increments at 30-min intervals to a maximum of 400 mg/hr.
- For previously untreated NHL and B-cell NHL, if no Grade 3 or 4 infusion-related reactions occurred in Cycle 1, may administer via 90-min infusion using glucocorticoids. Begin at rate of 20% of dose over 30 min, with remaining 80% dose over 60 min. If tolerated, then can be used for remainder of therapy.

Patient/Family Teaching ⬆ ⬇

Inform patient of the purpose of the medication. Advise patient to read the Medication Guide prior to starting therapy and before each infusion in case of changes.
Advise patient to report infusion-related events or symptoms of hypersensitivity reactions immediately.
Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; orthostatic hypotension; or painful ulcers or sores on your skin, lips, or in mouth, blisters, peeling skin, rash, pustule occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
Advise patient to consult health care professional prior to receiving any vaccinations.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 12 mo following therapy, and to avoid breastfeeding during and for at least 6 mo after last dose. Observe newborns and infants of women taking rituximab during pregnancy for signs of infection.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇