Obinutuzumab
FDA Drug Information • Also known as: Gazyva
- Brand Names
- Gazyva
- Drug Class
- CD20-directed Cytolytic Antibody [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION, CONCENTRATE
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY 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, including GAZYVA. Screen all patients for HBV infection before treatment initiation. Monitor HBV-positive patients during and after treatment with GAZYVA. Discontinue GAZYVA and concomitant medications in the event of HBV reactivation [see Warnings and Precautions (5.1) ] . Progressive Multifocal Leukoencephalopathy (PML) including fatal PML, can occur in patients receiving GAZYVA [see Warnings and Precautions (5.2) ] . WARNING: HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning. Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death. ( 5.1 ) Progressive Multifocal Leukoencephalopathy (PML) resulting in death. ( 5.2 )
Description
11 DESCRIPTION Obinutuzumab is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20 molecule found on B cells. The molecular mass of the antibody is approximately 150 kDa. GAZYVA (obinutuzumab) injection is produced by mammalian cell (CHO) suspension culture. GAZYVA was engineered to have reduced fucose content as compared to a typical IgG1 produced in CHO cells. GAZYVA is a sterile, clear, colorless to slightly brown, preservative-free liquid concentrate for intravenous use. GAZYVA is supplied at a concentration of 25 mg/mL in 1,000 mg single-dose vials. Each vial contains in 40 mL: 1,000 mg obinutuzumab, L-histidine (57.6 mg), L-histidine hydrochloride monohydrate (89.6 mg), trehalose dihydrate (3632 mg), and poloxamer 188 (8 mg). The pH is 6.0.
What Is Obinutuzumab Used For?
1 INDICATIONS AND USAGE GAZYVA is a CD20-directed cytolytic antibody indicated: in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). ( 1.1 , 14 ) in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with follicular lymphoma (FL)who relapsed after, or are refractory to, a rituximab-containing regimen. ( 1.2 , 14 ) in combination with chemotherapy followed by GAZYVA monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III or IV follicular lymphoma. ( 1.2 , 14 ) for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy ( 1.3 , 14 ) 1.1 Chronic Lymphocytic Leukemia (CLL) GAZYVA, in combination with chlorambucil, is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia. 1.2 Follicular Lymphoma (FL) GAZYVA, in combination with bendamustine followed by GAZYVA monotherapy, is indicated for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen . GAZYVA, in combination with chemotherapy followed by GAZYVA monotherapy in patients achieving at least a partial remission, is indicated for the treatment of adult patients with previously untreated stage II bulky, III or IV follicular lymphoma . 1.3 Lupus Nephritis (LN) GAZYVA is indicated for the treatment of adult patients with active lupus nephritis who are receiving standard therapy.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Premedicate for infusion-related reactions and tumor lysis syndrome. ( 2.1 , 5.3 , 5.4 ) Administer only as intravenous infusion. Do not administer as an intravenous push or bolus. ( 2.1 ) The recommended dosage for chronic lymphocytic leukemia is 100 mg on day 1 and 900 mg on day 2 of Cycle 1, 1,000 mg on day 8 and 15 of Cycle 1, and 1,000 mg on day 1 of Cycles 2–6. ( 2.2 ) The recommended dosage for follicular lymphoma is 1,000 mg on day 1, 8 and 15 of Cycle 1, 1,000 mg on day 1 of Cycles 2-6 or Cycles 2-8, and then 1,000 mg every 2 months for up to 2 years. ( 2.3 ) The recommended dosage for active lupus nephritis is 1,000 mg at the initial infusion, on Week 2, 24, 26, and every 6 months thereafter. ( 2.4 ) 2.1 Important Dosing Information Premedicate before each infusion [see Dosage and Administration (2.4) ] . Provide prophylactic hydration and anti-hyperuricemics to patients at high risk of tumor lysis syndrome [see Dosage and Administration (2.4) and Warnings and Precautions (5.4) ]. Administer only as an intravenous infusion through a dedicated line [see Dosage and Administration (2.6) ] . Do not administer as an intravenous push or bolus. Monitor blood counts at regular intervals. GAZYVA should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur [see Warnings and Precautions (5.3) ]. 2.2 Recommended Dosage for Chronic Lymphocytic Leukemia Each dose of GAZYVA is 1,000 mg administered intravenously with the exception of the first infusions in Cycle 1, which are administered on day 1 (100 mg) and day 2 (900 mg) according to Table 1 . Table 1 Dose of GAZYVA to be Administered During Six 28-Day Treatment Cycles for Patients with CLL Day of treatment cycle Dose of GAZYVA Rate of infusion Cycle 1 (loading doses) Day 1 100 mg Administer at 25 mg/hr over 4 hours. Do not increase the infusion rate. Day 2 900 mg If no infusion-related reaction (IRR) occurred during the previous infusion, administer at 50 mg/hr. The rate of the infusion can be escalated in increments of 50 mg/hr every 30 minutes to a maximum rate of 400 mg/hr. If an IRR occurred during the previous infusion, administer at 25 mg/hr. The rate of infusion can be escalated in increments of up to 50 mg/hr every 30 minutes to a maximum rate of 400 mg/hr. Day 8 1,000 mg If no IRR occurred during the previous infusion and the final infusion rate was 100 mg/hr or faster, infusions can be started at a rate of 100 mg/hr and increased by 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. If an infusion-related reaction occurred during the previous infusion, administer at 50 mg/hr. The rate of infusion can be escalated in increments of 50 mg/hr every 30 minutes to a maximum rate of 400 mg/hr. Day 15 1,000 mg Cycles 2 – 6 Day 1 1,000 mg If a planned dose of GAZYVA is missed, administer the missed dose as soon as possible and adjust dosing schedule...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatitis B virus reactivation [see Warnings and Precautions (5.1) ] Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.2) ] Infusion-related reactions [see Warnings and Precautions (5.3) ] Hypersensitivity reactions including serum sickness [see Warnings and Precautions (5.4) ] Tumor lysis syndrome [see Warnings and Precautions (5.5) ] Infections [see Warnings and Precautions (5.6) ] Neutropenia [see Warnings and Precautions (5.7) ] Thrombocytopenia [see Warnings and Precautions (5.8) ] Disseminated intravascular coagulation [see Warnings and Precautions (5.9) ] The most common adverse reactions (incidence ≥ 20% and ≥ 2% greater in the GAZYVA treated arm in CLL and NHL, and incidence ≥ 5% in the GAZYVA treated arm in LN) were: Previously untreated CLL : infusion-related reactions and neutropenia. ( 6 ) Relapsed or refractory non-Hodgkin lymphoma (NHL) : infusion-related reactions, fatigue, neutropenia, cough, upper respiratory tract infections, and musculoskeletal pain. ( 6 ) Previously untreated NHL : infusion-related reactions, neutropenia, upper respiratory tract infections, cough, constipation, and diarrhea. ( 6 ) Lupus Nephritis : upper respiratory tract infection, COVID-19, urinary tract infection, bronchitis, pneumonia, infusion-related reactions, and neutropenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Chronic Lymphocytic Leukemia The data below are based on a safety population of 773 previously untreated patients with CLL in the CLL11 study. Patients were treated with chlorambucil alone, GAZYVA in combination with chlorambucil, or rituximab product in combination with chlorambucil. The Stage 1 analysis compared GAZYVA in combination with chlorambucil vs. chlorambucil alone and Stage 2 compared GAZYVA in combination with chlorambucil vs. rituximab product in combination with chlorambucil. Adverse reactions rates and laboratory abnormalities from the Stage 2 phase are presented below and are consistent with the rates in Stage 1. In addition to the adverse reactions observed in Stage 2, in Stage 1, back pain (5% vs. 2%), anemia (12% vs. 10%) and cough (10% vs. 7%) were observed at a higher incidence in the GAZYVA treated patients. The incidence of Grade 3 to 4 back pain (< 1% vs. 0%), cough (0% vs. < 1%) and anemia (5% vs. 4%) was similar in both treatment arms. With regard to laboratory abnormalities, in Stage 1 hyperkalemia (33% vs. 18%), creatinine increased (30% vs. 20%) and alkaline phosphatase increased (18% vs. 11%) were observed at a higher incidence in patients treated with GAZYVA with similar incidences of Grade 3 to 4 abnormalities between the two arms. Patients received three 1,000 mg doses of GAZYVA on the first cycle and a single dose of 1,000 mg once every 28 days for 5 additional cycles in combination with chlorambucil (6 cycles of 28 days each in total). In the last 140 patients enrolled, the first dose of GAZYVA was split between day 1 (100 mg) and day 2 (900 mg) [see Dosage and Administration (2.2) ] . In total, 81% of patients received all 6 cycles (of 28 days each) of GAZYVA-based therapy. Adverse reactions in ≥ 10% of patients in the GAZYVA containing arm were infusion-related reactions, neutropenia, thrombocytopenia, and diarrhea. The most common Grade 3 to 4 adverse reactions (incidence ≥ 10%) in the GAZYVA containing arm were neutropenia, infusion-related reactions, and thrombocytopenia. Table 7 Adverse Reactions (Incidence ≥ 5% and ≥ 2% Greater in the GAZYVA Arm) in Patients...
Contraindications
4 CONTRAINDICATIONS GAZYVA is contraindicated in patients with known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or to any of the excipients, or serum sickness with prior obinutuzumab use [see Warnings and Precautions (5.4) ]. GAZYVA is contraindicated in patients with known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, GAZYVA can cause fetal B-cell depletion [see Clinical Pharmacology (12.1) ] . There are no data with GAZYVA use in pregnant women to inform a drug-associated risk. Monoclonal antibodies are transferred across the placenta. In animal reproduction studies, weekly intravenous 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 1,000 mg monthly produced opportunistic infections and immune complex mediated hypersensitivity reactions. No embryo-toxic or teratogenic effects were observed in the monkeys (see Data ) . Advise pregnant women of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with systemic lupus erythematosus (SLE) are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal LN increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. Fetal/Neonatal Adverse Reactions GAZYVA is likely to cause fetal B-cell depletion (see Data ) . Avoid administering live vaccines to neonates and infants exposed to GAZYVA in utero until B-cell recovery occurs [see Warnings and Precautions (5.11) and Clinical Pharmacology (12.2) ] . Data Animal Data In a pre- and post-natal development study, pregnant...
Overdosage
10 OVERDOSAGE There has been no experience with overdose in human clinical trials. For patients who experience overdose, treatment should consist of immediate interruption or reduction of GAZYVA and supportive therapy.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING GAZYVA (obinutuzumab) injection is a clear, colorless to slightly brown, preservative-free solution for intravenous use supplied as 1,000 mg/40 mL (25 mg/mL) in single-dose vials (NDC 50242-070-01). Store at 2°C to 8°C (36°F to 46°F). Do not use beyond expiration date stamped on carton. Protect from light. DO NOT FREEZE. DO NOT SHAKE.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.