obinutuzumab (Rx)

Brand and Other Names:Gazyva
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

IV solution

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

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 infused at 25 mg/hr over 4 hr; do not increase infusion rate
  • Day 2
    • 900 mg IV
    • No infusion reaction 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
    • Infusion reaction with previous infusion: Infuse at 25 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr
  • Days 8 and 15
    • 1000 mg IV
    • No infusion reaction 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
    • Infusion reaction 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

  • Day 1: 1000 mg IV
  • No infusion reaction 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
  • Infusion reaction with previous infusion: Infuse at 50 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr

Follicular Lymphoma

Indications

  • 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
  • In addition, for patients with untreated stage II bulky, III or IV follicular lymphoma; administer in combination with chemotherapy followed by obinutuzumab monotherapy
  • Previously untreated FL chemotherapy regimens
    • Six 28-day cycles in combination with bendamustine
    • Six 21-day cycles in combination with CHOP, followed by 2 additional 21-day cycles of obinutuzumab alone
    • Eight 21-day cycles in combination with CVP
    • Patients with previously untreated FL who achieve a complete response or partial response to initial 6 or 8 cycles should continue on obinutuzumab 1000 mg as monotherapy for up to 2 years

Cycle 1

  • Day 1: 1000 mg IV infuse at 50 mg/hr; may increase rate of infusion in 50 mg/hr increments q30 min, not to exceed 400 mg/hr
  • Day 8 and 15
    • 1000 mg IV
    • No infusion reaction or Grade 1 infusion reaction 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
    • Infusion reaction of ≥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

  • Day 1: 1000 mg IV
  • No infusion reaction or Grade 1 infusion reaction 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
  • Infusion reaction of ≥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

Monotherapy

  • 1000 mg IV q2months for up to 2 years
  • No infusion reaction or a Grade 1 infusion reaction 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
  • Infusion reaction of ≥Grade 2 with previous infusion, infuse at 50 mg/hr; may increase rate in 50 mg/hr increments q30min, not to exceed 400 mg/hr

Premedication

Premedicate before each infusion

For patients at high risk of tumor lysis syndrome, provide prophylactic hydration and antihyperuricemics (eg, allopurinol)

When glucocorticoids are indicated, use dexamethasone or methylprednisolone; hydrocortisone is not recommended as it has not been effective in reducing the rate of infusion reactions

Hypotension may occur during IV infusions; consider withholding antihypertensive agents for 12 hr prior to and throughout each obinutuzumab infusion and for the first hr after administration

For patients with high tumor burden and/or high circulating absolute lymphocyte counts, premedicate with antihyperuricemics (eg, allopurinol) 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; antiviral and antifungal prophylaxis should be considered

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 prior to obinutuzumab infusion
  • Acetaminophen 650-1000 mg PO; at least 30 min prior to obinutuzumab infusion
  • Diphenhydramine 50 mg IV/PO; at least 30 min prior to obinutuzumab infusion

All subsequent infusions

  • All patients: Acetaminophen 650-1000 mg PO; at least 30 min prior to obinutuzumab infusion
  • Infusion-related reaction (≥Grade 1) with previous infusion: Add diphenhydramine 50 mg IV/PO; cat least 30 min prior to obinutuzumab infusion
  • Infusion-related reaction (Grade 3) with previous infusion OR with a lymphocyte count >25 x 10^9/L prior to next treatment: Dexamethasone 20 mg IV or methylprednisolone 80 mg IV; complete administration at least 1 hr prior to obinutuzumab infusion

Dosage Modifications

Consider treatment interruption, if patients experience an infection, Grade 3 or 4 cytopenia, or a ≥Grade 2 nonhematologic toxicity

Infusion-related reactions

  • Grade 1-2 (mild-to-moderate): Reduce infusion rate or interrupt infusion and treat symptoms; upon resolution, continue/resume infusion and, if patient does not experience any further infusion reaction symptoms, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment cycle dose
  • Grade 1-2 for 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 (severe): Interrupt infusion and manage symptoms; upon resolution of symptoms, consider restarting infusion at ≤50% of the previous rate and, if patient does not experience any further infusion reaction symptoms, infusion rate escalation may resume at the increments and intervals as appropriate for the treatment cycle dose
  • Permanently discontinue treatment if patients experience a Grade 3 infusion related symptom upon rechallenge
  • Grade 3 for CLL patients only
    • Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hr, but not increased further
  • Grade 4 (life threatening): 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

Next:

Interactions

Interaction Checker

and obinutuzumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            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

            Previous
            Next:

            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

            None

            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

            May reactivate hepatitis B virus (see Black Box Warnings)

            Progressive multifocal leukoencephalopathy (PML) reported (see Black Box Warnings)

            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)

            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 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

            Safety and efficacy of immunization with live or attenuated viral vaccines during or following obinutuzumab therapy has 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 has also been reported, symptoms (eg, chest pain, diffuse arthralgia and fever)

            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
            Previous
            Next:

            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

            Lactation

            Unknown if distributed in human breast milk

            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.

            more...
            Previous
            Next:

            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

            Previous
            Next:

            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

            IV Administration

            Administer as IV infusion only

            Do not administer as IV push or bolus

            Do not mix with other drugs

            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

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            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.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous