- Treatment of previously untreated chronic lymphocytic leukemia (CLL) (in combination with chlorambucil).
- Treatment of follicular lymphoma in patients who have relapsed after, or are refractory to, a rituximab-containing regimen (in combination with bendamustine, followed by obinutuzumab monotherapy).
- Treatment of previously untreated stage II bulky, III, or IV follicular lymphoma (in combination with chemotherapy, followed by obinutuzumab monotherapy in patients achieving at least a partial remission).
Humanized anti-CD20 monoclonal IgG1 antibody, targeting an antigen found on the surface of pre and mature B- lymphocytes. Result is B-cell lysis and depletion.
Improved progression-free survival.
Absorption: IV administration results in complete bioavailability.
Metabolism and Excretion: Unknown.
Half-life: 28.4 days.
TIME/ACTION PROFILE (improvement progression-free survival)
|IV||within 3 mo||12 mo||unknown|
- Prior or concurrent live virus vaccinations;
- Active infection;
- Lactation: Avoid breastfeeding.
Use Cautiously in:
- Hepatitis B infection (may reactivate);
- OB: Use only if potential benefit outweighs fetal risks;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
GI: hypocalcemia, hypokalemia, hyponatremia
Hemat: NEUTROPENIA, THROMBOCYTOPENIA, anemia
MS: musculoskeletal disorder
Misc: INFUSION REACTIONS, BLEEDING, HYPERSENSITIVITY REACTIONS (INCLUDING BRONCHOSPASM, URTICARIA, AND SERUM SICKNESS), INFECTION (INCLUDING BACTERIAL, FUNGAL, AND VIRAL), TUMOR LYSIS SYNDROME, fever, hepatitis B reactivation
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- ↑ risk of immunosuppression/neutropenia with other antineoplastics, immunosuppressants or radiation therapy.
- May ↓ antibody response to and ↑ risk of adverse reactions from live virus vaccines (do not administer prior to or during treatment).
- Concurrent use of anticoagulants or antiplatelet agents , especially during the first cycle, may ↑ risk of bleeding.
Pre-medication is required. Cycles 1–6 (each cycle = 28 days) should also include chlorambucil.
IV (Adults): Day 1 of Cycle 1– 100 mg; Day 2 of Cycle 1– 900 mg; Days 8 and 15 of Cycle 1– 1000 mg; Day 1 of Cycles 2–6 1000 mg.
Relapsed or Refractory Follicular Lymphoma
Pre-medication is required. Cycles 1–6 should also include bendamustine.
IV (Adults): Days 1, 8, and 15 of Cycle 1– 1000 mg, Day 1 of Cycles 2–6– 1000 mg. If patient achieves disease stability, complete response, or partial response after 6 cycles, continue obinutuzumab as monotherapy as 1000 mg every 2 mo for up to 2 yr.
Previously Untreated Follicular Lymphoma
Pre-medication is required. May be administered for cycles 1–6 (each cycle = 28 days) with bendamustine; cycles 1–6 (each cycle = 21 days) with CHOP, followed by 2 additional cycles (each cycle = 21 days) of obinutuzumab monotherapy; or cycles 1–8 (each cycle = 21 days) with CVP).
IV (Adults): Days 1, 8, and 15 of Cycle 1– 1000 mg, Day 1 of Cycles 2–6 or Cycles 2–8– 1000 mg. If patient achieves disease stability, complete response, or partial response after 6–8 cycles, continue obinutuzumab as monotherapy as 1000 mg every 2 mo for up to 2 yr.
Solution for injection: 25 mg/mL
- Monitor patient with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several mo following therapy.
- Monitor for signs of PML (new onset or changes in pre-existing neurological signs and symptoms). Initiate evaluation for PML (neurological consultation, brain MRI, lumbar puncture) if signs occur. Discontinue obinutuzumab if PML is suspected.
- Assess for infusion-related reactions (hypotension, tachycardia, dyspnea, bronchospasm, larynx and throat irritation, wheezing, laryngeal edema, nausea, vomiting, diarrhea, hypertension, flushing, headache, pyrexia, chills) closely, especially during first 24 hrs. Premedicate and treat symptoms (glucocorticoids, epinephrine, bronchodilators, oxygen).
- Monitor patient for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia). Risks are higher in patients with greater tumor burden and rapidly proliferating tumors; may be fatal. Correct electrolyte abnormalities, hydrate patient, administer antihyperuricemic agents, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
Lab Test Considerations: Screen all patients for Hepatitis B virus (HBV) infection. For patients with evidence of hepatitis B infection (HBsAg positive or HBsAg negative but anti-HBc positive consult health care professional with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy.
- Monitor CBC frequently during therapy. May cause neutropenia; monitor for infection. Neutropenia may occur late onset, more than 28 days after completion of therapy and may be prolonged, lasting longer than 28 days. Consider antimicrobial prophylaxis (antiviral, antifungal) for patients with Grade 3–4 neutropenia >1 wk until resolution to Grade 1–2.
- Monitor platelet count frequently during therapy, especially during first cycle. May cause thrombocytopenia. May occur within 24 hr of infusion. May require platelet transfusion.
- Risk for infection (Adverse Reaction)
- Administration should be limited to health care professionals and facilities able to manage severe infusion reactions.
- Premedicate patients with a high tumor burden and/or high circulating absolute lymphocyte counts (>25 x 109 /L) with antihyperuricemics (allopurinol) beginning 12–24 hrs before starting therapy. Ensure adequate hydration for prophylaxis of tumor lysis syndrome.
- May cause hypotension. May require withholding antihypertensives for 12 hrs prior to and during each infusion and for first hr after infusion.
- Premedicate patients with neutropenia with antimicrobial prophylaxis and consider antiviral and antifungal prophylaxis. Consider interrupting therapy if infection, Grade 3 or 4 cytopenia, or a ≥Grade 2 non-hematologic toxicity occurs.
- Premedication Guidelines: Cycle 1: Day 1 and 2: Premedicate all patients with glucocorticoids IV: dexamethasone 20 mg or methylprednisolone 80 mg completed 1 hr prior to obinutuzumab infusion. Acetaminophen 650–1000 mg and antihistamine (diphenhydramine 50 mg) at least 30 min prior to infusion. Cycle 1: Day 8 and 15 and Cycle 2–6 Day 1: Premedicate all patients with acetaminophen 650–1000 mg at least 30 min before obinutuzumab infusion. Premedicate patients with ≥Grade 1 infusion reaction with previous infusion with antihistamine (diphenhydramine 50 mg) at least 30 min prior to infusion. Premedicate patients with a Grade 3 infusion-related reaction with previous infusion OR with a lymphocyte count >25 x 109 /L prior to next treatment with glucocorticoids IV: dexamethasone 20 mg or methylprednisolone 80 mg completed 1 hr prior to obinutuzumab infusion.
- Intermittent Infusion: Diluent: Dilute into 0.9% NaCl PVC or non-PVC polyolefin infusion bag. Do not use other diluents.
- Day 1 (100 mg) and Day 2 (900 mg) of Cycle 1:Withdraw 40 mL of obinutuzumab from vial. Dilute 4 mL (100 mg) into 100 mL of 0.9% NaCl infusion bag for immediate administration. Dilute remaining 36 mL (900 mg) into 250 mL of 0.9% NaCl infusion bag at same time for use on Day 2. Store in refrigerator for up to 24 hr. Infuse immediately after allowing bag to come to room temperature.
- Day 8 and 15 of Cycle 1 and Day 1 Cycles 2–6: Withdraw 40 mL of obinutuzumab from vial. Dilute 40 mL (1000 mg) into 250 mL of 0.9% NaCl. Gently invert to mix; do not shake or freeze. If not administered immediately, stable in refrigerator for up to 24 hrs. Concentration: 0.4 mg/mL to 4 mg/mL.
- Rate: Do not administer via IV push or bolus. Day 1; Cycle 1: Infuse at 25 mg/hr over 4 hrs. Do not increase infusion rate. Day 2; Cycle 1: Infuse at 50 mg/hr. Increase infusion rate in increments of 50 mg/hr every 30 min to a maximum of 400 mg/hr. Day 8 and 15; Cycle 1 and Day 1; Cycles 2–6: Infuse at 100 mg/hr and increase rate in 100 mg/hr increments every 30 min to a maximum of 400 mg/hr.
- If infusion reaction occurs adjust rate as follows: Grade 1–2 (mild to moderate): Reduce or interrupt rate and treat symptoms. Continue or resume infusion upon resolution of symptoms. If no further infusion reaction symptoms, rate increase may resume as planned; For CLL: Day 1 infusion rate may be increased back to 25 mg/hr after 1 hr but not increased further. Grade 3 (severe): Interrupt infusion and manage symptoms. Consider restarting infusion at one-half previous rate at time of interruption. If no further infusion reaction symptoms, rate increase may resume as planned. For CLL: Day 1 infusion rate may be increased back to 25 mg/hr after 1 hour but not increased further. Permanently discontinue if Grade 3 infusion reaction symptoms occur at re-challenge. Grade 4 (life-threatening): Stop infusion immediately and permanently discontinue.
- Y-Site Incompatibility: Infuse through a dedicated line.
- Additive Incompatibility: Do not mix with other drugs.
- Inform patient of purpose of obinutuzumab.
- Advise patient to avoid live viral vaccines during therapy
- Instruct patient to notify health care professional immediately if signs and symptoms of infusion reaction (dizziness, nausea, chills, fever, vomiting, diarrhea, breathing problems, chest pain), tumor lysis syndrome (nausea, vomiting, diarrhea, lethargy), infection (fever, cough), hepatitis (worsening fatigue, yellow discoloration of skin or eyes) or new changes in neurological symptoms (confusion, dizziness, loss of balance, difficulty talking or walking, vision problems) occur.
- Rep: Caution female patient to use effective contraception during and for at least 12 mo following therapy and to avoid breastfeeding. Advise patient to notify health care professional immediately if pregnancy occurs.
Decrease in progression of chronic lymphocytic leukemia and follicular lymphoma.
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