Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 100mg/5mL vial
- 1000mg/50mL vial
Chronic Lymphocytic Leukemia
Previously untreated
- In combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate
- Cycle 1: 300 mg IV on Day 1 followed 1 week later by 1,000 mg on Day 8, THEN
- Subsequent 28-day cycles: 1,000 mg on Day 1 for a minimum of 3 cycles until best response or a maximum of 12 cycles
Relapsed CLL
- Indicated in combination with fludarabine and cyclophosphamide for relapsed CLL
- Dose 1: 300 mg IV, followed 1 week later by
- Dose 2: 1,000 mg IV, followed by
- Dose 3 and thereafter: 1,000 mg on Day 1 of subsequent 28-day cycles for maximum of 6 cycles
Extended treatment
- Indicated for extended treatment as a single agent in patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL
- Dose 1: 300 mg IV on Day 1, followed 1 week later by
- Dose 2: 1,000 mg 1 week on Day 8, followed 7 weeks later by
- Dose 3 and thereafter: 1,000 mg IV and then q8wk thereafter for up to a maximum of 2 yr
Refractory CLL
- Indicated for CLL refractory to fludarabine and alemtuzumab
- Dose 1: 300 mg IV, followed 1 week later by
- Doses 2-8: 2,000 mg IV qWeek for 7 doses, followed 4 weeks later by
- Doses 9-12: 2,000 mg IV q4Weeks for 4 doses
- Regimen totals 12 doses
Safety and efficacy not established
Adverse Effects
>10%
Neutropenia
Pneumonia
Pyrexia
Cough
Diarrhea
Anemia
Fatigue
Dyspnea
Rash
Nausea
Bronchitis
Upper respiratory tract infections
<10%
Infusion reaction/complication
Cytopenias
Infection (pneumonia, sepsis)
Progressive multifocal leukoencephalopathy
Hepatitis B reactivation
Intestinal obstruction
Warnings
Black Box Warnings
Progressive multifocal leukoencephalopathy (PML) including fatal PML, can occur in patients receiving obinutuzumab
Hepatitis B virus reactivation
- Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed cytolytic antibodies
- Screen all patients for HBV infection before treatment initiation
- Monitor HBV positive patients during and after treatment
- Discontinue ofatumumab and concomitant medications in the event of HBV reactivation
Contraindications
Hypersensitivity
Cautions
Increased susceptibility to infection
May increase risk for progressive multifocal leukoencephalopathy (PML)
Fulminant and fatal hepatitis B infection and reactivation reported following treatment; closely monitor HBV carriers for clinical and laboratory signs of active HBV infection during treatment and for 6-12 months following last infusion
Infusion reaction may occur, monitor closely
Neutropenia
Thrombocytopenia
Intestinal obstruction of small intestine
Tumor lysis syndrome (TLS) reported, including the need for hospitalization; patients with high tumor burden and/or high circulating lymphocyte counts (>25 x 10^9/L) are at greater risk; consider TSL prophylaxis with antihyperuricemics and hydration beginning 12-24 hr before infusion
Do not administer live virus vaccines (inability to generate immune response)
Pregnancy & Lactation
Pregnancy Category: C
Lactation: unknown whether distributed in breast milk; published data suggest neonate/infant does not ingest substantial amount of these maternal antibodies from breast milk, although caution is warranted
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Anti-CD20 human monoclonal antibody that inhibits B-cell activation in early stages
Pharmacokinetics
Half-Life: 14 days (mean between 4th-12th infusions)
Cmax: 63 mcg/mL (after 1st dose); 1482 mcg/mL (after 8th dose); 881 mcg/mL (after 12th dose)
Vdss: 3.2 L (after 1st dose); 5.1 L (after 8th dose); 4.7 L after 12th dose
Clearance: 0.01 L/hr (mean clearance between 4th-12th infusions)
Administration
IV Compatibilities
Solution: 0.9% NaCl
IV Preparation
Do NOT shake product
IV infusion: Prepare all doses in 1000-mL polyolefin bag of 0.9% NaCl
300 mg dose: Withdraw and discard 15 mL from 1000 mL 0.9% NaCl; add measured dose to IV bag; yields 300 mg/L = 0.3 mg/mL
1,000 mg dose: Withdraw and discard 50 mL from 1000 mL 0.9% NaCl; add measured dose to IV bag; yields 1,000 mg/L = 1 mg/mL
2000 mg dose: Withdraw and discard 100 mL from 1000 mL 0.9% NaCl; add measured dose to IV bag; yields 2000 mg/L = 2 mg/mL
IV Administration
Premedicate with corticosteroid, analgesic, and antihistamine before each infusion to avoid infusion-related reactions
Administer by slow IV infusion and use in-line filter supplied with product via volumetric infusion pump; do NOT administer as IV push or bolus
Previously untreated and extended treatment CLL
- For initial 300 mg dose: Initiate IV infusion at rate of 3.6 mg/hr (12 mL/hr)
- For subsequent 1,000 mg doses: Initiate IV infusion at rate of 25 mg/hr (25 mL/hr); initiate infusion at a rate of 12 mg/hr if a ≥grade 3 infusion-related adverse event was experienced during the previous infusion
- In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes by 12-25 mL/hr; not to exceed 400 mL/hr
Refractory CLL
- Dose 1 (300 mg dose): Initiate IV infusion at rate of 3.6 mg/hr (12 mL/hr)
- Dose 2 (2,000 mg dose): Initiate IV infusion at a rate of 24 mg/hr (12 mL/hr)
- Doses 3-12 (2,000 mg dose): Initiate IV infusion at a rate of 50 mg/hr (25 mL/hr)
- In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes by 12-25 mL/hr; not to exceed 200 mL/hr for doses 1-2, and 400 mL/hr for doses 3-12
Storage
Store undiluted vials refrigerated (between 36-46 degrees F); protect from light
Store diluted solution refrigerated (between 36-46 degrees F)
Start infusion within 12 hr of preparation
Discard prepared solution after 24 hr
Images
Patient Handout
Formulary
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