Obinutuzumab

Obinutuzumab is a prescription medication used for the treatment of chronic lymphocytic leukemia.

• in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).
• in combination with bendamustine followed by obinutuzumab monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen
• in combination with chemotherapy followed by obinutuzumab 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
• for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy.

Obinutuzumab is available under the following different brand names: Gazyva

Common side effects of the Obinutuzumab include:

• infusion-related reactions
• neutropenia
• fatigue 
• cough
• upper respiratory tract infections
• urinary tract infection
• musculoskeletal pain
• constipation
• diarrhea
• COVID-19, 
• bronchitis
• pneumonia

Serious side effects of Obinutuzumab include:

• hepatitis B virus reactivation
• progressive multifocal leukoencephalopathy (PML)
• severe infusion-related reactions 
• hypersensitivity reactions, including serum sickness
• tumor lysis syndrome 
• serious infections, including fatal infections
• neutropenia
• thrombocytopenia
• disseminated intravascular coagulation (DIC)

Rare side effects of the Obinutuzumab include:

• none

This is not a complete list of side effects and other serious side effects or health problems that may occur due to the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

IV solution

• 25mg/mL (1000mg/40mL single-use vial)

Chronic Lymphocytic Leukemia

Adult dosage

• 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

Adult dosage

• Relapsed or refractory to 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
  • 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 a complete response or partial response to initial 6 or 8 cycles is achieved, continue 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 a complete or partial response is achieved, continue with obinutuzumab 1000 mg every 2 months as monotherapy for up to 2 years

Monotherapy

• 1000 mg IV every 2 months for up to 2 years

Lupus Nephritis

Adult dosage

• Dose 1: 1000 mg IV
• Dose 2: 1000 mg IV administered 2 weeks after dose 1
• Dose 3 (Week 24): 1000 mg IV
• Dose 4 (Week 26): 1000 mg IV administered 2 weeks after dose 3
• Dose 5 and thereafter: 1000 mg IV administered 6 months after dose 4, and then every 6 months afterwards

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to the drug or excipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Obinutuzumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Obinutuzumab?”

Cautions

• Anticipate tumor lysis syndrome; premedicate with anti-hyperuricemic 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
• May reactivate hepatitis B virus (see Black Box Warnings)
• Progressive multifocal leukoencephalopathy (PML) was reported (see Black Box Warnings)
• Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia from tumor lysis syndrome (TLS) can occur within 12-24 hours after the first infusion (see Premedication)
• Serious bacterial, fungal, and new or reactivated viral infections can occur; do not give obinutuzumab with an active infection
• Neutropenia may occur (in combination with chlorambucil, Grade 3 or 4 neutropenia was reported in 34% of patients); patients with neutropenia are strongly recommended to receive antimicrobial prophylaxis throughout the treatment period; antiviral and antifungal prophylaxis should be considered
• Thrombocytopenia may occur (in combination with chlorambucil, Grade 3 or 4 neutropenia reported in 12% of patients); monitor all patients frequently for thrombocytopenia and hemorrhagic events, especially during the first cycle; management of hemorrhage may require blood product support
• The 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 have been reported; signs of immediate onset hypersensitivity (eg, dyspnea, bronchospasm, hypotension, urticaria, and tachycardia); late-onset hypersensitivity diagnosed as serum sickness have also been reported, and symptoms (eg, chest pain, diffuse arthralgia, and fever)
• Progressive multifocal leukoencephalopathy (PML)
  • 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 by monotherapy of this drug, Grade 3 to 5 infections are reported
  • Do not administer therapy to patients with an active infection; patients with a history of recurring or chronic diseases 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 (above 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 hours 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 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, an increase in transaminase levels and, in severe cases, an 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 the 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 the safety of resuming therapy in patients who develop HBV reactivation

Pregnancy and Lactation

• There are no data on 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
• The 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 the last dose
• Lactation
  • Unknown if distributed in human breast milk; because of the potential of serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 6 months after the 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 the breastfed infant