ri-TUX-i-mab/hye-al-yoor-ON-i-dase

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

• Relapsed or refractory follicular lymphoma (as monotherapy).
• Previously untreated follicular lymphoma 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 follicular lymphoma following treatment with cyclophosphamide, vincristine, and prednisone (as monotherapy).
• Previously untreated diffuse large B-cell lymphoma (in combination with CHOP or another anthracycline-based chemotherapy regimen).
• Previously untreated chronic lymphocytic leukemia (CLL) (in combination with fludarabine and cyclophosphamide).

• Rituximab — Binds to the CD20 antigen on the surface of lymphoma cells, preventing the activation process for cell cycle initiation and differentiation; hyaluronidase — acts locally by depolymerizing hyalyonan, which increases permeability of the subcutaneous tissue.

• Death of lymphoma and leukemia cells.

Absorption: 64% absorbed following subcutaneous administration.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Unknown.

Half-life: 32–34 hr.

(B-cell depletion)

Contraindicated in:

• Hypersensitivity to murine (mouse) proteins
• OB: Can pass placental barrier potentially causing fetal B-cell depletion. Give only if clearly needed during pregnancy
• Lactation: Lactation (potential for immunosuppression in infant).

Use Cautiously in:

• Hepatitis B infection (may reactivate infection during and for several mo after treatment)
• Underlying cardiac or pulmonary disease, history of cardiopulmonary reaction to rituximab, or high numbers of circulating malignant cells (25,000/mm³)
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: ARRHYTHMIAS, CARDIOGENIC SHOCK, MI, chest pain, hypertension, peripheral edema.

Derm: MUCOCUTANEOUS SKIN REACTIONS, alopecia, pruritus.

GI: BOWEL OBSTRUCTION/PERFORATION, HEPATITIS B REACTIVATION, abdominal pain, constipation, diarrhea, nausea, vomiting, ↓ appetite, dyspepsia, stomatitis.

GU: RENAL FAILURE.

Hemat: neutropenia, anemia, thrombocytopenia, leukopenia, lymphopenia.

Local: injection site reactions.

Metab: ↓weight.

MS: arthralgia, muscle spasms, myalgia.

Neuro: peripheral neuropathy , PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, headache, dizziness, insomnia.

Resp: cough, dyspnea.

Misc: infection, infusion reactions, CYTOKINE RELEASE SYNDROME, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), TUMOR LYSIS SYNDROME, fatigue, fever.

Drug-Drug:

• May ↓ antibody response to and ↑ risk of adverse reactions from live vaccines; avoid use during therapy.

Follicular Lymphoma

All patients must receive 1 full dose of rituximab by IV infusion before starting treatment with subcutaneous product.

• SC (Adults): Relapsed or refractory disease — rituximab 1,400 mg/hyaluronidase 23,400 units once weekly starting Week 2 (one wk after receiving treatment with full dose of IV rituximab) for 3 or 7 wk (4 or 8 wk, respectively, of total therapy including IV rituximab); Retreatment for relapsed or refractory disease — rituximab 1,400 mg/hyaluronidase 23,400 units once weekly starting Week 2 (one wk after receiving treatment with full dose of IV rituximab) for 3 wk (4 wk of total therapy including IV rituximab); Previously untreated disease — rituximab 1,400 mg/hyaluronidase 23,400 units on Day 1 of Cycles 2–8 of chemotherapy (every 21 days) for up to 7 cycles following treatment with full dose of IV rituximab (given on Day 1 of Cycle 1 of chemotherapy) (total of 8 cycles including IV rituximab); if complete or partial response achieved, give rituximab 1,400 mg/hyaluronidase 23,400 units (as monotherapy) every 8 wk for 12 doses (initiate 8 wk after completion of combination treatment with chemotherapy); Non-progressing disease after first–line CVP chemotherapy — rituximab 1,400 mg/hyaluronidase 23,400 units once weekly for 3 wk following completion of 6–8 cycles of CVP chemotherapy and a full dose of IV rituximab at Week 1; administer at 6 month intervals to a maximum of 16 doses.

Diffuse Large B-Cell Lymphoma

All patients must receive 1 full dose of rituximab by IV infusion in combination with CHOP chemotherapy before starting treatment with subcutaneous product.

• SC (Adults): Rituximab 1,400 mg/hyaluronidase 23,400 units on Day 1 of Cycles 2–8 of CHOP chemotherapy for up to 7 cycles; full dose of IV rituximab should be administered on Day 1 of Cycle 1 of CHOP chemotherapy.

CLL

All patients must receive 1 full dose of rituximab by IV infusion in combination with fludarabine and cyclophosphamide chemotherapy before starting treatment with subcutaneous product.

• SC (Adults): Rituximab 1,600 mg/hyaluronidase 26,800 units on Day 1 of Cycles 2–6 (every 28 days) for a total of 5 cycles; full dose of IV rituximab should be administered on Day 1 of Cycle 1 of fludarabine/cyclophosphamide chemotherapy.

• Solution for injection: rituximab 120 mg and hyaluronidase 2,000 units/mL;

• Assess patient for hypersensitivity reactions (hypotension, bronchospasm, angioedema) during administration and for at least 15 min after injection, especially patients with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (25,000/mm³). Interrupt injection immediately and treat aggressively if reaction occurs. Epinephrine, antihistamines, and corticosteroids should be readily available in the event of a severe reaction.
• Monitor for signs and symptoms of local cutaneous hypersensitivity reactions (pain, swelling, induration, hemorrhage, erythema, pruritus, rash) following injection. May occur more than 24 hr after injection. Most reactions are mild to moderate and resolved without specific 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.
• 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 injection. 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 patient for signs and symptoms of infection (fever, chills/rigors, nausea, urticaria, fatigue, headache, pruritus, bronchospasm, dyspnea, sensation of tongue or throat swelling, rhinitis, vomiting, hypotension, flushing, pain at disease sites).
• Assess for signs of progressive multifocal leukoencephalopathy (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) periodically during therapy.
• Monitor ECG during and immediately after infusion in patients with pre-existing cardiac conditions (arrhythmias, angina). Life-threatening arrhythmias may occur. Discontinue therapy if significant arrhythmias occur.
• Monitor for signs and symptoms of renal failure (↑ serum creatinine, oliguria) periodically during therapy.
• Assess for signs and symptoms of bowel obstruction (abdominal pain, repeated vomiting) during therapy.

• Verify a negative pregnancy test before starting therapy.
  • 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.
  • May cause anemia, neutropenia, and leukopenia.

• Do not confuse Rituxan Hycela (rituximab/hyaluronidase) with Rituxan (rituximab).
• Patients must receive at least 1 full dose of rituximab IV without experiencing severe adverse reactions before starting rituximab/hyaluronidase.
• Premedicate with an antihistamine and acetaminophen prior to each injection.
• SC: Solution is clear to opalescent and colorless to yellowish; do not administer solution that are cloudy, discolored, or contain particulate matter. Solution is stable for 48 hrs if refrigerated and 8 hrs at room temperature. Inject into abdomen over 5 for 11.7 mL dose and over 7 min for 13.4 mL dose. Avoid red, bruised, tender, hard areas and moles or scars. If injection is interrupted, continue administering at same site, or at a different site, but restrict to the abdomen. Do not inject other subcut medication in same area.

• Explain purpose of medication to patient. Advise patient to read Medication Guide prior to starting therapy and before each injection in case of changes.
• Advise patient to report signs 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 skin, lips, or in mouth, blisters, peeling skin, rash, pustule occurs.
• Advise patient to live vaccines during therapy.
• Discuss with patient the possibility of hair loss. Explore methods of coping.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
• Rep: Instruct females of reproductive potential to use effective contraception during therapy and for 12 mo following last dose, and to avoid breast feeding for at least 6 mo after last dose. Advise patient to notify health care professional if pregnancy is suspected.

• Decrease in spread of malignancy.

Rituxan Hycela

Rituxan SC

• Risk for infection (Adverse Reactions).
• Risk for impaired skin integrity (Adverse Reactions).

NDC Code^*

• 50242- Genentech, Inc.
  • 50242-108- Rituxan Hycela
    • 50242-108-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-108-01) > 11.7 mL in 1 VIAL, SINGLE-DOSE

• 50242- Genentech, Inc.
  • 50242-108- Rituxan Hycela
    • 50242-108-86- 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-108-86) > 11.7 mL in 1 VIAL, SINGLE-DOSE

• 50242- Genentech, Inc.
  • 50242-109- Rituxan Hycela
    • 50242-109-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-109-01) > 13.4 mL in 1 VIAL, SINGLE-DOSE