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 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;
- Nonprogressing 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 granulomatosis) and microscopic polyangiitis (in combination with glucocorticoids);
- Moderate to severe pemphigus vulgaris.

Rituxan only

Treatment of the following condition:
- 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;
Pre-existing cardiac or pulmonary conditions, history of rituximab-induced cardiopulmonary adverse reactions, or high numbers of circulating malignant cells (↑ risk of infusion-related reactions)
;
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, LICHENOID DERMATITIS, PARANEOPLASTIC PEMPHIGUS, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria, VESICULOBULLOUS DERMATITIS

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: infection, INFUSION-RELATED 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 Lymphoma

IV (Adults ): Riabni, Rituxan, Ruxience, or Truxima: 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 Lymphoma

IV (Adults ): Riabni, Rituxan, Ruxience, or Truxima: 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).

Nonprogressing Low-Grade CD20-Positive B-Cell Non-Hodgkin Lymphoma

IV (Adults ): Riabni, Rituxan, Ruxience, or Truxima: 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 Lymphoma

IV (Adults ): Riabni, Rituxan, Ruxience, or Truxima: 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): Rituxan: 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 ): Riabni, Rituxan, Ruxience, or Truxima: 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 ): Riabni, Rituxan, Ruxience, or Truxima: 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: Riabni, Rituxan, Ruxience, or Truxima: 375 mg/m² once weekly for 4 wk; Follow-up treatment in patients who have achieved disease control with induction treatment: Riabni, Rituxan, Ruxience, or Truxima: 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: Riabni, Rituxan, Ruxience, or Truxima: 375 mg/m² once weekly for 4 wk; Follow-up treatment in patients who have achieved disease control with induction treatment: Riabni, Rituxan, Ruxience, or Truxima: 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 ): Riabni, Rituxan, Ruxience, or Truxima: 1000 mg every 2 wk for 2 doses, then maintenance dose of 500 mg infusion at Month 12 and then every 6 mo thereafter. On relapse, administer 1000 mg.

Availability ⬆ ⬇

Solution for injection: 10 mg/mL
In combination with: hyaluronidase (Rituxan Hycela). See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Monitor for signs/symptoms of infusion-related reactions (fever, chills/rigors, nausea, urticaria, fatigue, headache, pruritus, bronchospasm, dyspnea, sensation of tongue or throat swelling, rhinitis, vomiting, hypotension, flushing, pain at disease sites, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, cardiogenic shock). Infusion-related events occur frequently within 30 min–2 hr of beginning 1st infusion and may resolve with slowing or discontinuing infusion. If severe reactions occur, immediately discontinue infusion and treat with glucocorticoids, epinephrine, bronchodilators, or oxygen, as needed. If decision is made to restart rituximab after symptoms resolve, resume infusion at ≥50% ↓ in rate. Incidence ↓ with subsequent infusions.
Monitor for tumor lysis syndrome due to rapid ↓ in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, 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.
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, 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 concurrent 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, or eosinophilia.

Lab Test Considerations:

Verify negative pregnancy status before starting therapy. Monitor CBC 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 ↑ 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 1–3 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; 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 ≥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. Unused portion of Ruxience diluted in 0.9% NaCl can be stored refrigerated for 16 days.
Rate: Do not administer as an IV push or bolus.
- 1st infusion: Administer at an initial rate of 50 mg/hr. If hypersensitivity or infusion-related events do not occur, rate may ↑ in 50-mg/hr increments every 30 min to a maximum of 400 mg/hr.
- Subsequent infusions: May administer at an initial rate of 100 mg/hr and ↑ in 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.
Y-Site Compatibility:
- acyclovir
- amikacin
- aminophylline
- ampicillin
- ampicillin/sulbactam
- aztreonam
- bleomycin
- bumetanide
- buprenorphine
- busulfan
- butorphanol
- calcium gluconate
- carboplatin
- carmustine
- cefazolin
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chlorpromazine
- cisplatin
- clindamycin
- cyclophosphamide
- cytarabine
- dactinomycin
- daunorubicin
- dexamethasone
- dexrazoxane
- digoxin
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin liposomal
- 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
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- mesna
- methotrexate
- methylprednisolone
- metoclopramide
- metronidazole
- mitomycin
- mitoxantrone
- morphine
- nalbuphine
- paclitaxel
- pentamidine
- piperacillin/tazobactam
- potassium chloride
- prochlorperazine
- promethazine
- sargramostim
- theophylline
- thiotepa
- tobramycin
- trimethoprim/sulfamethoxazole
- vinblastine
- vincristine
- vinorelbine
- zidovudine
Y-Site Incompatibility:
- aldesleukin
- ciprofloxacin
- cyclosporine
- doxorubicin hydrochloride
- furosemide
- levofloxacin
- minocycline
- ondansetron
- sodium bicarbonate
- topotecan
- vancomycin

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient to report signs/symptoms infusion-related reactions immediately.
Instruct patient to notify health care provider promptly if painful ulcers or sores on skin, lips, or in mouth; blisters; peeling skin; rash; or pustule occur.
Instruct patient to report signs/symptoms of hepatotoxicity (yellowing of the skin and eyes, unusual darkening of the urine, nausea, feeling tired or weak, vomiting) that persist over several days to health care provider immediately.
Instruct patient to report signs/symptoms of PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes) that persist over several days to health care provider immediately.
Instruct patient to notify health care provider 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; ↑ fatigue; dyspnea; or orthostatic hypotension 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 provider prior to receiving any vaccinations.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for 12 mo following therapy and to avoid breastfeeding during therapy and for ≥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 ⬆ ⬇