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Pharmacologic class: Murine/human monoclonal antibody
Therapeutic class: Antineoplastic
Pregnancy risk category C
FDA Box Warning
• Deaths from infusion reactions have occurred within 24 hours of rituximab infusion. Approximately 80% of fatal reactions were linked to first infusion. If severe infusion reaction develops, discontinue infusion and intervene appropriately.
• Acute renal failure requiring dialysis, severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy have been reported.
Binds to CD20 antigen on malignant B lymphocytes; recruits immune effector functions to mediate B-cell lysis (possibly through complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity)
Injection: 10 mg/ml in 10-ml (100-mg) and 50-ml (500-mg) vials
Indications and dosages
➣ Non Hodgkin's lymphoma (NHL)
Adults: 375 mg/m2 by I.V. infusion according to the following schedules:
Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL: Give weekly for four or eight doses.
Retreatment for relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL: Give weekly for four doses.
Previously untreated, follicular, CD20-positive, B-cell NHL: Give on day 1 of each cycle of cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy, for up to eight doses.
Non-progressing, low-grade, CD20-positive B-cell NHL, after first line CVP chemotherapy: Following completion of six to eight cycles of CVP chemotherapy, give weekly for four doses at 6-month intervals to a maximum of 16 doses.
Diffuse large B-cell NHL: Give on day 1 of each cycle of chemotherapy for up to eight infusions.
Dosage in combination with ibritumomab: On day 1, rituximab 250 mg/m2 by I.V. infusion. Within 4 hours after rituximab infusion, give 5 mCi In-111 ibritumomab I.V. On days 7, 8, and 9, give rituximab 250 mg/m2 by I.V. infusion and platelet-count-dependent dose of Y-90 ibritumomab I.V.
➣ Moderately to severely active rheumatoid arthritis in patients who have had an inadequate response to one or more tumor necrosis factor antagonist
Adults: Two 1,000 mg I.V. infusions separated by 2 weeks in combination with methotrexate. Give subsequent courses every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks.
➣ Chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide (FC)
Adults: 375 mg/m2 I.V. day before start of FC chemotherapy; then 500 mg/m2 on day 1 of cycles 2 to 6 (every 28 days).
• Waldenström's macroglobulinemia
• Hypersensitivity to drug, its components, or murine products
Use cautiously in:
• history of drug allergy or sensitivity
• previous exposure to murine-based monoclonal antibodies
• high level of circulating malignant cells
• cardiac or pulmonary conditions
• pregnant or breastfeeding patients
• Follow facility policy regarding handling, administration, and disposal of chemotherapeutic drugs.
• Know that Pneumocystis jiroveci pneumonia and antiherpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment, as appropriate.
• To reduce the incidence and severity of infusion reactions, premedicate patient with diphenhydramine and acetaminophen, as prescribed. In addition, for patients with rheumatoid arthritis, give I.V. methylprednisolone (or its equivalent) 30 minutes before each infusion.
• Consider withholding antihypertensive agents 12 hours before giving drug to help prevent hypotension.
• Give drug as I.V. infusion.
☞ Never give as I.V. bolus or I.V. push.
• Don't mix or dilute with other drugs.
• Dilute in dextrose 5% in water (D5W) or normal saline solution to a concentration of 1 to 4 mg/ml. Invert bag gently to mix solution.
• Administer the first infusion at an initial rate of 50 mg/hr. If no infusion reaction occurs, increase the infusion rate in 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.
• If the patient tolerates the first infusion well, administer subsequent infusions at an initial rate of 100 mg/hr and increase by 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr, as tolerated.
☞ Be aware that a severe infusion reaction may occur usually after first infusion. This reaction consists of a complex of hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, M.I., ventricular fibrillation, or cardiogenic shock. If such a reaction occurs, stop infusion immediately and treat appropriately.
• If hypersensitivity reaction (non-IgE-mediated) or infusion reaction that is not severe occurs, interrupt or temporarily slow infusion. When symptoms improve, infusion can continue at half of previous rate.
CNS: dizziness, headache, nervousness, hypertonia, hyperesthesia, insomnia, agitation, malaise, paresthesia, asthenia, fatigue, tremor, rigors
CV: hypotension, hypertension, peripheral edema, chest pain, tachycardia, bradycardia, angina, arrhythmias
EENT: conjunctivitis, lacrimation disorders, rhinitis, sinusitis, pharyngitis
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, anorexia
GU: renal toxicity
Hematologic: anemia, neutropenia, leukopenia, thrombocytopenia
Metabolic: hyperglycemia, hypocalcemia
Musculoskeletal: myalgia, back pain
Respiratory: dyspnea, cough, bronchitis, bronchospasm
Skin: pruritus, rash, urticaria, flushing, dermatitis, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome
Other: altered taste, fever, chills, pain at injection site, hypersensitivity reactions including sepsis, severe infusion reaction
Drug-drug. Cisplatin: increased risk of renal failure
Live-virus vaccines: increased risk of infection from vaccine
Drug-diagnostic tests. Calcium, hemoglobin, neutrophils, platelets, white blood cells: decreased values
Glucose, lactate dehydrogenase: increased levels
• Monitor closely for signs and symptoms of hypersensitivity reaction.
☞ Stop drug immediately and notify prescriber if patient develops signs or symptoms of Stevens-Johnson syndrome or other severe mucocutaneous reactions (including severe rash).
☞ Monitor pulse and blood pressure throughout I.V. infusion. Stop infusion if hypotension, bronchospasm, or angioedema occurs. Then consult prescriber about restarting infusion at half of previous rate.
☞ Monitor ECG throughout infusion. Stop infusion if serious arrhythmia develops.
• Monitor CBC, blood glucose, and electrolyte levels.
• Assess for signs and symptoms of infection, including fever.
☞ Tell patient to immediately report signs and symptoms of hypersensitivity reaction or severe skin reaction.
☞ Instruct patient to take his temperature daily and immediately report fever and other signs or symptoms of infection.
☞ Instruct patient to immediately report unusual bleeding or bruising.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
Pharmacologic: monoclonal antibodies
Time/action profile (B-cell depletion)
|IV||within 14 days||3–4 wk||6–9 mo†|
Adverse Reactions/Side Effects
Central nervous system
- progressive multifocal leukoencephalopathy (life-threatening)
- arrhythmias (life-threatening)
- hypotension (most frequent)
- peripheral edema
- abdominal pain
- altered taste
- renal failure
- mucocutaneous skin reactions (life-threatening)
Fluid and Electrolyte
- anemia (life-threatening)
- neutropenia (life-threatening)
- thrombocytopenia (life-threatening)
- back pain
- allergic reactions including anaphylaxis and angioedema (life-threatening)
- hepatitis b reactivation (life-threatening)
- infusion reactions (life-threatening)
- tumor lysis syndrome (life-threatening)
- fever/chills/rigors (infusion related)
Drug-Drug interactionNone known.
Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL
Previously Untreated Follicular, CD20–Positive, B-Cell NHL
Non-Progressing Low-Grade, CD20-Positive, B-Cell NHL
Diffuse Large B-Cell NHL
GPA and MPA
- 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 first 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 first 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 patient for 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 progressive multifocal leukoencephalopathy (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 hepatitis B 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 Stevens-Johnson syndrome and toxic epidermal necrolysis. 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: Monitor CBC and platelet count 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 hepatitis B up to 24 mo after therapy.
Potential Nursing DiagnosesRisk for infection (Side Effects)
- Do not confuse rituximab with infliximab.
- 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.
- GPA and MPA: 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 WG and MPA.
- Intermittent Infusion: Diluent: Dilute with 0.9% NaCl or D5W.Concentration: 1–4 mg/mL. Gently invert bag to mix. Solution is clear and colorless; do not administer solutions that are 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 non-Hodgkins lymphoma and B-cell non-Hodgkin’s lymphoma, 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.
- Y-Site Compatibility: acyclovir, amifostine, amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonan, bleomycin, bumetanide, buprenorphine, busulfan, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chlorproamzine, cisplatin, clindamycin, cyclophosphamide, cytarabine, dactinomycin, daunarubicin hydrochloride, dexamethasone sodium phosphate, dexrazoxane, digoxin, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin liposome, doxycycline, droperidol, enalaprilat, etoposide phosphate, famotidine, fentanyl, filgrastim, floxuridine, fluconazole, fludarabine, fluorouracil, ganciclovir, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, irinotecan, leucovorin, levorphanol, lorazepam, magnesium sulfate, mannitol, meperidine, mesna, methotrexate, methyprednisolone, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, paclitaxel, pentamidine, piperacillin/tazobactam, potassium chloride, prochlorperazine, promethazine, ranitidine, sargramostim, streptozocin, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tobramycin, trimethoprim/sulfamethoxazole, vinblastine, vincristine, vinorelbine, zidovudine
- Y-Site Incompatibility: aldesleukin, amphotericin B colloidal, ciprofloxacin, cyclosporine, daunorubicin liposome, doxorubicin hydrochloride, furosemide, levofloxacin, minocycline, ondansetron, quinapristin/dalfopristin, sodium bicarbonate, topotecan, vancomycin
- Additive Incompatibility: Do not admix with other medications.
- 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.
- Instruct patient to use effective contraception during therapy and for 12 mo following therapy, and to avoid breast feeding.
- Decrease in spread of malignancy.
- Reduced signs and symptoms of rheumatoid arthritis.
- Achievement of complete remission in GPA and MPA.