Dosing & Uses
Dosage Forms & Strengths
IV solution
- 25mg/mL (1000mg/40mL single-use vial)
Chronic Lymphocytic Leukemia
Indicated for previously untreated chronic lymphocytic leukemia in combination with chlorambucil
Administer for 6 treatment cycles (28-day cycles)
Cycle 1
- Day 1: 100 mg IV
- Day 2: 900 mg IV
- Days 8 and 15: 1000 mg IV
Cycles 2-6
- Day 1: 1000 mg IV
Follicular Lymphoma
Relapsed or refractory to rituximab-containing regimen
- Indicated for patients with follicular lymphoma (FL) who relapsed after, or are refractory to a rituximab-containing regimen; administer in combination with bendamustine (six 28-day cycles) followed by obinutuzumab monotherapy for up to 2 years
Previously untreated stage II bulky, III or IV FL
- Indicated for patients with untreated stage II bulky, III or IV FL in combination with chemotherapy followed by obinutuzumab monotherapy
- Six 28-day cycles in combination with bendamustine, OR
- Six 21-day cycles in combination with CHOP, followed by 2 additional 21-day cycles of obinutuzumab alone, OR
- Eight 21-day cycles in combination with CVP
- If complete response or partial response to initial 6 or 8 cycles achieved, continue on obinutuzumab 1000 mg monotherapy for up to 2 years
Dosage regimen
- Cycle 1: 1000 mg IV on Days 1, 8, and 15
- Cycles 2-6 or 2-8: 1000 mg IV on Day 1
- If complete or partial response achieved, continue with obinutuzumab 1000 mg q2Months as monotherapy for up to 2 years
Monotherapy
- 1000 mg IV q2months for up to 2 years
Dosage Modifications
Consider treatment interruption, if an infection, Grade 3 or 4 cytopenia, or a Grade ≥2 nonhematologic toxicity occurs
Infusion-related reactions
Grade 1-2
- Reduce infusion rate or interrupt infusion and treat symptoms; upon resolution, continue/resume infusion and, if no further IRR occurs, infusion rate escalation may resume at increments and intervals as appropriate for treatment cycle dose
- CLL patients only: Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hr, but not increased further
Grade 3
- Interrupt infusion and manage symptoms; upon resolution of symptoms, consider restarting infusion at ≤50% of previous rate and, if no further IRR occurs, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment cycle dose
- CLL only: Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hr, but not increased further
- FL with Grade 3 IRRs during 90-minute infusion: Upon resolution of symptoms, restart infusion at no more than half the previous rate (rate used at the time that IRR occurred) and not to exceed 400 mg/hr; subsequent infusions at the standard rate
- Permanently discontinue treatment if Grade ≥3 infusion related symptom if rechallenged
Grade 4
- Stop infusion immediately and permanently discontinue
Marginal Zone Lymphoma (Orphan)
Orphan designation for treatment of splenic marginal zone lymphoma
Sponsor
- Genentech, Inc; 1 DNA Way, MS# 214A; South San Francisco, CA 94080-4990
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (10)
- axicabtagene ciloleucel
obinutuzumab, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- brexucabtagene autoleucel
obinutuzumab, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ciltacabtagene autoleucel
obinutuzumab, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- deferiprone
deferiprone, obinutuzumab. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- idecabtagene vicleucel
obinutuzumab, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- lisocabtagene maraleucel
obinutuzumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- palifermin
palifermin increases toxicity of obinutuzumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, obinutuzumab. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- tisagenlecleucel
obinutuzumab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ublituximab
ublituximab and obinutuzumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Each drug is an anti-CD20 monoclonal antibody indicated for multiple sclerosis.
Monitor Closely (32)
- adenovirus types 4 and 7 live, oral
obinutuzumab decreases effects of adenovirus types 4 and 7 live, oral by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- amifostine
amifostine, obinutuzumab. Either decreases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Hypotension may occur during administration. Consider withholding antihypertensive treatments for 12 hr before and during each obinutuzumab infusion and for the first hour after administration.
- BCG vaccine live
obinutuzumab decreases effects of BCG vaccine live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- benazepril
obinutuzumab increases effects of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Obinutuzumab may enhance the hypotensive effect of blood pressure lowering agents.
- captopril
obinutuzumab, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.
- chlorambucil
chlorambucil increases toxicity of obinutuzumab by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reported to cause thrombocytopenia and subsequent hemorrhage that may require blood product support.
- cholera vaccine
obinutuzumab, cholera vaccine. immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- dengue vaccine
obinutuzumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- dichlorphenamide
dichlorphenamide and obinutuzumab both decrease serum potassium. Use Caution/Monitor.
- efgartigimod alfa
efgartigimod alfa will decrease the level or effect of obinutuzumab by receptor binding competition. Use Caution/Monitor. Coadministration of efgartigimod with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- efgartigimod/hyaluronidase SC
efgartigimod/hyaluronidase SC will decrease the level or effect of obinutuzumab by receptor binding competition. Use Caution/Monitor. Coadministration of efgartigimod with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- haemophilus influenzae type b vaccine
obinutuzumab decreases effects of haemophilus influenzae type b vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response may be suboptimal. Patients on chemotherapy with anti-B cell antibodies should wait =6 months after therapy before being vaccinated with inactivated vaccines.
- influenza virus vaccine quadrivalent, intranasal
obinutuzumab decreases effects of influenza virus vaccine quadrivalent, intranasal by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- measles (rubeola) vaccine
obinutuzumab decreases effects of measles (rubeola) vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- measles mumps and rubella vaccine, live
obinutuzumab decreases effects of measles mumps and rubella vaccine, live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- measles, mumps, rubella and varicella vaccine, live
obinutuzumab decreases effects of measles, mumps, rubella and varicella vaccine, live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- ofatumumab SC
ofatumumab SC, obinutuzumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.
- poliovirus vaccine inactivated
obinutuzumab decreases effects of poliovirus vaccine inactivated by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response may be suboptimal. Patients on chemotherapy with anti-B cell antibodies should wait =6 months after therapy before being vaccinated with inactivated vaccines.
- rotavirus oral vaccine, live
obinutuzumab decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- rozanolixizumab
rozanolixizumab will decrease the level or effect of obinutuzumab by receptor binding competition. Use Caution/Monitor. Coadministration of rozanolixizumab with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing rozanolixizumab and using alternative therapies.
- rubella vaccine
obinutuzumab decreases effects of rubella vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- siponimod
siponimod and obinutuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- smallpox (vaccinia) vaccine, live
obinutuzumab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- trastuzumab
trastuzumab, obinutuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- trastuzumab deruxtecan
trastuzumab deruxtecan, obinutuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- typhoid polysaccharide vaccine
obinutuzumab decreases effects of typhoid polysaccharide vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- typhoid vaccine live
obinutuzumab decreases effects of typhoid vaccine live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- varicella virus vaccine live
obinutuzumab decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- warfarin
obinutuzumab increases effects of warfarin by anticoagulation. Use Caution/Monitor.
- yellow fever vaccine
obinutuzumab decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- zoster vaccine live
obinutuzumab decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunization with live virus vaccines is not recommended during obinutuzumab treatment and until after B-cell recovery.
- zoster vaccine recombinant
obinutuzumab decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant.
Minor (0)
Adverse Effects
>10%
Infusion related reactions (69%)
Neutropenia (33%)
Hypocalcemia (32%)
Hyperkalemia (31%)
Hyponatremia (29%)
Creatinine increased (28%)
AST/SGOT increased (28%)
AST/SGPT increased (25%)
Hypoalbuminemia (16%)
Alkaline phosphatase increased (16%)
Thrombocytopenia (15%)
Hypokalemia (13%)
Anemia (12%)
1-10%
Pyrexia (10%)
Cough (10%)
Leukopenia (7%)
Tumor lysis syndrome (2%)
Postmarketing Reports
Hypophosphatemia
Diarrhea
Headache
Insomnia
Pruritus
Serum sickness
Chronic lymphocytic leukemia
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 obinutuzumab and concomitant medications in the event of HBV reactivation
Contraindications
Hypersensitivity to drug or excipients
Cautions
Anticipate tumor lysis syndrome; premedicate with anti-hyperuricemics and adequate hydration especially for patients with high tumor burden and/or high circulating lymphocyte count; correct electrolyte abnormalities, provide supportive care, and monitor renal function and fluid balance
Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia from tumor lysis syndrome (TLS) can occur within 12-24 hr after the first infusion (see Premedication)
Safety and efficacy of immunization with live or attenuated viral vaccines during or following obinutuzumab therapy have not been studied; immunization with live virus vaccines is not recommended during treatment and until B-cell recovery
Hypersensitivity reactions reported; signs of immediate onset hypersensitivity (eg, dyspnea, bronchospasm, hypotension, urticaria, and tachycardia); late-onset hypersensitivity diagnosed as serum sickness have also been reported, symptoms (eg, chest pain, diffuse arthralgia and fever)
Progressive multifocal leukoencephalopathy
- Consider diagnosis of PML in any patient presenting with new onset or changes to preexisting neurologic manifestations; evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture
- Discontinue therapy and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML
Infections
- Fatal and serious bacterial, fungal, and new or reactivated viral infections can occur during and following therapy; when this drug is administered with chemotherapy followed bymonotherapy of this drug Grade 3 to 5 infections reported
- Do not administer therapy to patients with an active infection; patients with a history of recurring or chronic infections may be at increased risk of infection
Neutropenia
- Severe and life-threatening neutropenia, including febrile neutropenia, reported during treatment; monitor patients with Grade 3-4 neutropenia frequently with regular laboratory tests until resolution
- Anticipate, evaluate, and treat any symptoms or signs of developing infection; consider dose delays for Grade 3 or 4 neutropenia; consider administration of granulocyte colony-stimulating factors (GCSF) in patients with Grade 3 or 4 neutropenia
- Neutropenia can be of late onset (occurring more than 28 days after completion of treatment) and/or prolonged (lasting longer than 28 days); patients with severe and long-lasting (> 1 week)neutropenia are strongly recommended to receive antimicrobial prophylaxis until resolution of neutropenia to Grade 1 or 2; consider antiviral and antifungal prophylaxis
Thrombocytopenia
- Thrombocytopenia may occur (in combination with chlorambucil, Grade 3 or 4 neutropenia reported in 12% of patients); in patients with Grade 3 or 4 thrombocytopenia, monitor platelet counts more frequently until resolution and consider dose delays of this drug and chemotherapy or dose reductions of chemotherapy
- Monitor all patients frequently for thrombocytopenia and hemorrhagic events, especially during the first cycle; if clinically indicated, evaluate laboratory coagulation parameters
- Transfusion of blood products (eg, platelet transfusion) may be necessary; consider withholding concomitant medications that may increase bleeding risk (platelet inhibitors, anticoagulants), especially during the first cycle
Disseminated intravascular coagulation (DIC)
- Fatal and severe DIC reported
- If DIC is suspected, evaluate potential causes, and monitor coagulation parameters, platelet counts, and for signs and symptoms of bleeding or thrombosis
- Manage according to standard guidelines for DIC
- Supportive care, including transfusion of blood products and other medical management, may be necessary
Infusion-related reactions
- May cause severe and life-threatening infusion reactions (see Dosage Modification and Premedication sections)
- Patients with pre-existing cardiac or pulmonary conditions are at greater risk of severe reactions
- Monitor closely throughout the infusion and the post-infusion period; interrupt or discontinue infusion for reactions
- Due to the risk of infusion induced hypotension, consider withholding antihypertensive treatments for 12 hr prior to, during , and for the first hour after administration until blood pressure is stable
- Consider the benefits versus the risks of withholding their antihypertensive medication in patients who are at increased of hypertensive crisis
Hepatitis B virus reactivation
- Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with anti-CD20 antibodies
- HBV reactivation has been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive
- Reactivation has also occurred in patients who appear to have resolved hepatitis B infection (eg, HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [anti-HBs] positive);
- HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive
- Reactivation of HBV replication is often followed by hepatitis, eg, increase in transaminase levels and, in severe cases, increase in bilirubin levels, liver failure, and death
- Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with this drug; for patients who show evidence of hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult healthcare providers with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy
- Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment
- HBV reactivation has been reported for other CD20-directed cytolytic antibodies following completion of therapy;in patients who develop reactivation of HBV while receiving therapy, immediately discontinue drug and any concomitant chemotherapy and institute appropriate treatment
- Resumption of therapy in patients whose HBV reactivation resolves should be discussed with healthcare providers with expertise in managing hepatitis B; insufficient data exist regarding safety of resuming in patients who develop HBV reactivation
Pregnancy & Lactation
Pregnancy
There are no data with obinutuzumab use in pregnant women to inform a drug-associated risk
Based on findings from animal studies and the drug’s mechanism of action, obinutuzumab may cause fetal B-cell depletion
Avoid administering live vaccines to neonates and infants exposed to obinutuzumab in utero until B-cell recovery occurs
In animal reproduction studies, weekly IV administration of obinutuzumab to pregnant cynomolgus monkeys from day 20 of pregnancy until parturition which includes the period of organogenesis at doses with exposures up to 2.4 times the exposure at the clinical dose of 1000 mg monthly produced opportunistic infections and immune complex mediated hypersensitivity reactions
Drug can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 6 months after last dose
Lactation
Unknown if distributed in human breast milk; because of potential of serious adverse reactions in breastfed child, advise women not to breastfeed during treatment and for 6 months after last dose
Excreted in the milk of lactating cynomolgus monkeys and human IgG is known to be excreted in human milk; consider developmental and health benefits along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant
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
CD20-directed cytolytic antibody; upon binding to CD20, obinutuzumab mediates B-cell lysis through 1) engagement of immune effector cells, 2) by directly activating intracellular death signaling pathways and/or, 3) activation of the complement cascade
CD20 antigen is expressed on the surface of pre B- and mature B-lymphocytes; the immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis
Distribution
Vd: 3.8 L
Elimination
Half-life: 28.4 days
Clearance: 0.09 L/day
Administration
IV Compatibility
0.9% NaCl
IV Preparation
Inspect visually for any particulate matter and discoloration prior to administration
Dilute into 0.9% NaCl PVC or non-PVC polyolefin infusion bag
Do not use other diluents (eg, dextrose 5%)
Dilute under appropriate aseptic conditions
100 mg and 900 mg doses
- Withdraw 40 mL of solution from the vial
- Dilute 4 mL (100 mg) into 100 mL 0.9% NaCl infusion bag for immediate administration
- Dilute the remaining 36 mL (900 mg) into a 250 mL 0.9% sodium chloride infusion bag at the same time for use on Day 2
- After allowing the diluted bag to come to room temperature, use immediately
- Clearly label each infusion bag
1000 mg dose
- Withdraw 40 mL of solution from the vial
- Dilute 40 mL (1000 mg) into a 250 mL 0.9% NaCl infusion bag
- Mix diluted solution by gentle inversion; do not shake
- For microbiological stability, the diluted infusion solution should be used immediately
- The product can be administered at a final concentration of 0.4 mg/mL to 4 mg/mL
- If not used immediately, diluted solution may be refrigerated at 2-8°C (36-46°F) for up to 24 hours prior to use
Premedication
Premedicate before each infusion
When glucocorticoids are indicated, use dexamethasone or methylprednisolone; hydrocortisone is not recommended as it has not been effective in reducing infusion-related reactions (IRR)
Hypotension may occur during IV infusions; consider withholding antihypertensive agents for 12 hr before and throughout each infusion and for 1 hr after administration
For patients with high tumor burden, renal impairment, and/or high circulating absolute lymphocyte counts, premedicate with antihyperuricemics (eg, allopurinol, rasburicase) beginning 12-24 hr before initiating therapy and ensure adequate hydration for prophylaxis of tumor lysis syndrome
Patients with neutropenia are strongly recommended to receive antimicrobial prophylaxis throughout the treatment period; consider antiviral and antifungal prophylaxis for patients with severe and long lasting (>1 week) neutropenia
Cycle 1
- CLL Days 1 and 2 or FL Day 1
- Dexamethasone 20 mg IV or methylprednisolone 80 mg IV; complete administration at least 1 hr before infusion
- Acetaminophen 650-1000 mg PO; at least 30 min before infusion
- Diphenhydramine 50 mg IV/PO; at least 30 min before infusion
Subsequent infusions
- All patients: Acetaminophen 650-1000 mg PO; at least 30 min before infusion
- Infusion-related reaction Grade ≥1 with previous infusion: Add diphenhydramine 50 mg IV/PO; at least 30 min before infusion
- Grade 3 IRR with previous infusion OR with lymphocyte count >25 x 109/L before next treatment: Dexamethasone 20 mg IV or methylprednisolone 80 mg IV; complete administration at least 1 hr before infusion
IV Administration
Administer as IV infusion only
Do not administer as IV push or bolus
Do not mix with other drugs
Infusion rates (CLL)
-
Cycle 1 Day 1
- Day 1: Infuse at 25 mg/hr over 4 hr; do not increase infusion rate
-
Cycle 1 Day 2
- No IRR with previous infusion: Infuse at 50 mg/hr; may increase rate of infusion in 50 mg/hr increments q30min, not to exceed 400 mg/hr
- IRR with previous infusion: Infuse at 25 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr
-
Cycle 1 Days 8 and 15 and thereafter
- No IRR with previous infusion: Infuse at 100 mg/hr or faster; may increase rate of infusion in 100 mg/hr increments q30min, not to exceed 400 mg/hr
- IRR with previous infusion: Infuse at 50 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr
Infusion rates (FL)
-
Combination therapy
- Cycle 1 Day 1: Infuse at 50 mg/hr; may increase rate of infusion in 50 mg/hr increments q30 min, not to exceed 400 mg/hr
- Cycle 1 Days 8 and 15; No IRR with previous infusion and final infusion rate ≥100 mg/hr: Infuse at 100 mg/hr and may increase by 100 mg/hr increments q30min, not to exceed 400 mg/hr
- IRR Grade ≥2 occurred with previous infusion: Infuse at 50 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr
-
Cycles 2-6, 2-8, monotherapy
- No infusion reaction or Grade 1 IRR with previous infusion and final infusion rate was ≥100 mg/hr: Infuse at 100 mg/hr and may increase by 100 mg/hr increments q30min, not to exceed 400 mg/hr
- IRR Grade ≥2 occurred with previous infusion: Infuse at 50 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr
- No Grade ≥3 IRR during Cycle 1: May infuse over 100 mg/hr for 30 min, then 900 mg/hr for ~60 min
- IRR of Grade 1-2 with ongoing symptoms or a Grade ≥3 IRR occurred during previous approximately 90-minute infusion, administer all subsequent infusions at standard infusion rate
Missed dose
-
Chronic lymphocytic leukemia
- If a planned dose is missed, administer the missed dose as soon as possible and adjust dosing schedule accordingly
- If appropriate, patients who do not complete the Day 1 Cycle 1 dose may proceed to the Day 2 Cycle 1 dose
-
Follicular lymphoma
- Obinutuzumab and chemotherapy treatment: Adjust dosing schedule accordingly to maintain time interval between chemotherapy cycles
- Obinutuzumab monotherapy: Maintain original dosing schedule for subsequent doses; monotherapy should be initiated ~2 months after the last dose of obinutuzumab administered during the induction phase
Storage
Do not freeze or shake either unopened vials or diluted solution
Unopened vials: Store between 2-8°C [36-46°F]) in original carton and protect from light
Reconstituted vials and diluted solutions: Store in a refrigerator at 2-8°C (36-46°F) for up to 24 hr
Images
Patient Handout
obinutuzumab intravenous
OBINUTUZUMAB - INJECTION
(OH-bi-nue-TOOZ-ue-mab)
COMMON BRAND NAME(S): Gazyva
WARNING: Obinutuzumab may cause serious (possibly fatal) liver disease in people who have a current or past infection with hepatitis B. Before starting treatment with this medication, your doctor should order a test to see if you have hepatitis B. Your doctor may also order blood tests and watch for symptoms of liver disease during treatment and for several months after your last dose of medication. Get medical help right away if you have any symptoms of liver damage, including: nausea/vomiting that doesn't stop, loss of appetite, dark urine, stomach/abdominal pain, yellowing eyes/skin.Obinutuzumab may increase your risk of getting a rare but very serious (sometimes fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if any of these rare but very serious side effects occur: confusion, dizziness, loss of balance, difficulty talking/walking, vision changes.
USES: Obinutuzumab is used to treat certain types of blood cancer (such as chronic lymphocytic leukemia, follicular lymphoma). Obinutuzumab belongs to a class of drugs known as monoclonal antibodies. It works by stopping the growth of cancer cells.
HOW TO USE: This medication is given by injection into a vein by a health care professional. It is given as directed by your doctor. Your doctor may direct you to receive this medication in a treatment cycle (for example, only on certain days each month). Carefully follow your doctor's instructions.The dosage is based on your medical condition and response to treatment.Obinutuzumab may cause very serious infusion-related reactions during or up to 24 hours after treatment. These reactions occur more often with the first and second treatments. Your doctor will monitor you closely and increase your dose slowly to reduce the chance of these serious side effects. Your doctor may also prescribe other medications before each treatment, including acetaminophen, an antihistamine (such as diphenhydramine), and a corticosteroid (such as methylprednisolone) to prevent these side effects. If you have a reaction, your treatment may be temporarily stopped. Tell your doctor or nurse right away if any of these side effects occur: dizziness, fainting, fast heartbeat, chest pain, trouble breathing, wheezing, itching/swelling of the throat, nausea, vomiting, diarrhea, flushing, headache, fever, or chills.If you take drugs for high blood pressure, ask your doctor ahead of time if you should change the way you take your blood pressure medication right before and after your dose of obinutuzumab. Some people have had reactions (such as dizziness/fainting) due to taking blood pressure medication too close to the time of their obinutuzumab infusion.
SIDE EFFECTS: See also Warning and How to Use sections.Cough or joint/muscle pain may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following symptoms: unusual tiredness, pale skin, signs of infection (such as sore throat that doesn't go away, fever, chills), easy bruising/bleeding.Obinutuzumab sometimes causes side effects due to the rapid destruction of cancer cells (tumor lysis syndrome). To lower your risk, your doctor may add a medication and tell you to drink plenty of fluids. Tell your doctor right away if you have symptoms such as: low back/side pain (flank pain), signs of kidney problems (such as painful urination, pink/bloody urine, change in the amount of urine), muscle spasms/weakness.Get medical help right away if you have any very serious side effects, including: chest pain, pain/swelling/warmth in the groin/calf.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using obinutuzumab, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease (such as hepatitis B), active/current infection, heart disease, kidney disease, lung disease.Obinutuzumab can make you more likely to get infections or may make current infections worse. Stay away from anyone who has an infection that may easily spread (such as chickenpox, COVID-19, measles, flu). Talk to your doctor if you have been exposed to an infection or for more details.Tell your health care professional that you are using obinutuzumab before having any immunizations/vaccinations. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using obinutuzumab. Obinutuzumab may harm an unborn baby. Ask about reliable forms of birth control while using this medication and for 6 months after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.This medication may pass into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this medication and for 6 months after stopping treatment. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab).
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab tests (such as kidney function, complete blood count) should be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.
STORAGE: Not applicable. This medication is given in a hospital or clinic and will not be stored at home.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Information last revised March 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
