Rituxan


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Related to Rituxan: Herceptin, Avastin

riTUXimab

(ri-tux-i-mab) ,

Rituxan

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: monoclonal antibodies
Pregnancy Category: C

Indications

genetic implication Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) as a single agent.genetic implication 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.genetic implication Non-progressing, low-grade, CD20-positive, B-cell NHL as monotherapy following treatment with cyclophosphamide, vincristine, and prednisolone (CVP).genetic implication Previously untreated diffuse large B-cell, CD20–positive, NHL in combination with CHOP or another anthracycline-based chemotherapy regimen.genetic implication CD-20 positive chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide (FC).Moderately-to-severely active rheumatoid arthritis with methotrexate in patients who have had an inadequate response to one of more TNF antagonist therapies.Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in combination with glucocorticoids.

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 GPA and MPA.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Binds specifically to CD20 binding sites on lymphoma cells.
Metabolism and Excretion: Unknown.
Half-life: 59.8–174 hr (depending on tumor burden).

Time/action profile (B-cell depletion)

ROUTEONSETPEAKDURATION
IVwithin 14 days3–4 wk6–9 mo†
†Duration of depletion after 4 wk of treatment.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to murine (mouse) proteins; Obstetric: Can pass placental barrier potentially causing fetal B-cell depletion. Give only if clearly needed; Lactation: Potential for immunosuppresion in infant. Discontinue nursing.
Use Cautiously in: Pre-existing bone marrow depression;Hepatitis B infection (may reactivate infection during and for several months after treatment);Systemic lupus erythematosus (may cause fatal progressive multifocal leukoencephalopathy);HIV infection (may increase risk of HIV-associated lymphoma); Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • progressive multifocal leukoencephalopathy (life-threatening)
  • headache

Respiratory

  • bronchospasm
  • cough
  • dyspnea

Cardiovascular

  • arrhythmias (life-threatening)
  • hypotension (most frequent)
  • peripheral edema

Gastrointestinal

  • abdominal pain
  • altered taste
  • dyspepsia

Genitourinary

  • renal failure

Dermatologic

  • mucocutaneous skin reactions (life-threatening)
  • flushing
  • urticaria

Endocrinologic

  • hyperglycemia

Fluid and Electrolyte

  • hypocalcemia

Hematologic

  • anemia (life-threatening)
  • neutropenia (life-threatening)
  • thrombocytopenia (life-threatening)

Musculoskeletal

  • arthralgia
  • back pain

Miscellaneous

  • 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)
  • infections

Interactions

Drug-Drug interaction

None known.

Route/Dosage

Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL

Intravenous (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 NHL

Intravenous (Adults) 375 mg/m2 given on Day 1 of each cycle of CVP 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 + CVP regimen).

Non-Progressing Low-Grade, CD20-Positive, B-Cell NHL

Intravenous (Adults) For patients who have not progressed following 6–8 cycles of CVP chemotherapy, 375 mg/m2 given once weekly for 4 doses given every 6 mo for up to 16 doses.

Diffuse Large B-Cell NHL

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

CLL

Intravenous (Adults) 375 mg/m2 given on the day before initiating FC chemotherapy, then 500 mg/m2 on Day 1 of cycles 2–6 (every 28 days).

Rheumatoid Arthritis

Intravenous (Adults) Two 1000 mg infusions separated by 2 wk.

GPA and MPA

Intravenous (Adults) 375 mg/m2 once weekly for 4 wk.

Availability

Solution for injection (requires dilution): 10 mg/mL

Nursing implications

Nursing 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 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 Diagnoses

Risk for infection (Side Effects)

Implementation

  • 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.
  • Intravenous Administration
  • 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.

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.
  • Instruct patient to use effective contraception during therapy and for 12 mo following therapy, and to avoid breast feeding.

Evaluation/Desired Outcomes

  • Decrease in spread of malignancy.
  • Reduced signs and symptoms of rheumatoid arthritis.
  • Achievement of complete remission in GPA and MPA.

Rituxan

(rĭ-tŭk′sən)
A trademark for the drug rituximab.

Rituxan

® Rituximab Oncology A humanized mouse antibody used to treat relapsed or refractory low-grade or follicular B-cell NHL. See Humanized antibody.
References in periodicals archive ?
Zydelig s safety and effectiveness to treat relapsed CLL were established in a clinical trial of 220 participants who were randomly assigned to receive Zydelig and Rituxan or placebo and Rituxan.
health regulator approved Rituxan, in combination with glucocorticoids (steroids), to treat patients with Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA).
The safety and effectiveness of Rituxan was demonstrated in a single controlled trial, in which 197 patients with WG or MPA were assigned at random to receive either Rituxan plus glucocorticoids once a week for four weeks or oral cyclophosphamide plus glucocorticoids daily to induce remission.
which Roche fully acquired earlier this year, Rituxan is approved for use in both non-Hodgkin's lymphoma and rheumatoid arthritis.
Comment: Rituxan is a monoclonal antibody directed at the CD20 antigen, present on the surface of normal and malignant B lymphocytes and expressed on more than 90% of B-cell NHLs, but not on hematopoietic stem cells or normal plasma cells.
In a Phase 2 study evaluating patients with follicular NHL who did not respond to or responded inadequately to RITUXAN, ZEVALIN produced an overall response rate of 74 percent, with 15 percent of patients achieving a complete remission (disappearance of all evidence of disease), according to International Workshop Response Criteria (IWRC).
CLL11 is a three-arm study that compares GA101 plus chlorambucil to Rituxan plus chlorambucil or chlorambucil alone.
Rituxan is administered with two other chemotherapy drugs, fludarabine and cyclophosphamide.
Make more informed business decisions from insightful and in-depth analysis of Rituxan performance
The study showed that Rituxan was not inferior to the current standard of care, cyclophosphamide (CYC) in inducing disease remission at six months in adults with WG and MPA.
Genentech Inc (South San Francisco CA) and Biogen Idec Inc's (Cambridge MA) cancer drug Rituxan reduced brain lesions in multiple sclerosis patients and cut their risk of relapse, offering a potential new way to slow the disease.
Preliminary Safety Data on TNF Antagonist Use Following Rituxan Treatment Also Being Presented at the American College of Rheumatology Meeting -