Obinutuzumab

Name: Obinutuzumab

Uses of Obinutuzumab

Obinutuzumab is a prescription medication used to treat patients with chronic lymphocytic leukemia (CLL). CLL is a type of cancer that affects your white blood cells. White blood cells help your body fight infections.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information. 

Obinutuzumab Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of obinutuzumab, there are no specific foods that you must exclude from your diet when receiving this medication.

 

Obinutuzumab and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if obinutuzumab crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using obinutuzumab.

 

Obinutuzumab Dosage

The recommended dose of obinutuzumab, for the treatment of chronic lymphocytic leukemia (CLL), is 1000 mg, administered intravenously. However, the dose given for the first infusions in cycle 1 are 100 mg (day 1) and 900 mg (day 2).

 

 

What other drugs will affect obinutuzumab?

Other drugs may interact with obinutuzumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Interactions for Obinutuzumab

No formal drug interaction studies to date.1

Uses of Obinutuzumab

  • It is used to treat a type of leukemia.
  • It is used to treat a type of lymphoma.

Brand Names U.S.

  • Gazyva

Dosing Geriatric

Refer to adult dosing.

Dosing Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied)

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Severe and life-threatening (grade 3 and 4) neutropenia (including neutropenic fever) has been observed in clinical trials. Neutropenia may have a late onset (>28 days after therapy completion) and/or be prolonged (duration >28 days). Consider administration of granulocyte colony-stimulating factors in patients who develop grade 3 or 4 neutropenia. Monitor for signs/symptoms of infection; antimicrobial prophylaxis is recommended in neutropenic patients with severe neutropenia that lasts more than 1 week (continue prophylaxis until neutropenia improves to ≤ grade 2). Antiviral and/or antifungal prophylaxis should also be considered. Severe and life-threatening thrombocytopenia has also been reported when used in combination with chlorambucil or bendamustine. In a small percentage of patients, thrombocytopenia occurred acutely (within 24 hours) after obinutuzumab administration; platelet transfusions may be necessary. Fatal hemorrhagic events during the first cycle of therapy for CLL have been reported; monitor frequently for thrombocytopenia and bleeding episodes, particularly during the initial cycle. Thrombocytopenia may require dose delays of obinutuzumab and chemotherapy and/or dose reductions of chemotherapy. Consider withholding platelet inhibitors, anticoagulants, or other medications which may increase bleeding risk (especially during the first cycle). Leukopenia, lymphopenia, and anemia commonly occur. Monitor blood counts frequently throughout therapy.

• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation may occur with use of CD20-directed cytolytic antibodies (including obinutuzumab) and may result in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prior to therapy initiation; monitor patients for clinical and laboratory signs of hepatitis or HBV during and for several months after treatment. Discontinue obinutuzumab (and concomitant chemotherapy) if viral hepatitis develops and initiate appropriate antiviral therapy. Reactivation has occurred in patients who are HBsAg positive as well as in those who are HBsAg negative but are anti-HBc positive; HBV reactivation has also been observed in patients who had previously resolved HBV infection. HBV reactivation has been reported for other CD20-directed antibodies after therapy discontinuation. Reactivation of HBV replication is often followed by hepatitis. Use cautiously in patients who show evidence of prior HBV infection (eg, HBsAg positive [regardless of antibody status] or HBsAG negative but anti-HBc positive); consult with appropriate clinicians regarding monitoring and consideration of antiviral therapy before and/or during obinutuzumab treatment. The safety of resuming obinutuzumab treatment following HBV reactivation is not known; discuss reinitiation of therapy in patients with resolved HBV reactivation with physicians experienced in HBV management.

American Society of Clinical Oncology (ASCO) provisional clinical opinion update on hepatitis B virus screening recommendations (Hwang 2015): Patients receiving anti-CD20 antibodies are at high risk for HBV reactivation. Screen for HBV infection with HBsAG and anti-HBc tests prior to treatment initiation; either a total anti-HBc (with both immunoglobulin G [IgG] and immunoglobulin M [IgM]) or anti-HBc IgG test should be used to screen for chronic or resolved HBV infection (do not use anti-HBc IgM, as it may only confirm acute HBV infection). In addition, patients who have risk factors for HBV infection (eg, birthplace in a country with ≥2% HBV prevalence, household or sexual contact with HBV-infected patients, high-risk behaviors [eg, intravenous drug use], and HIV infection) should also be screened prior to beginning therapy. Initiate prophylactic antiviral therapy (utilizing antivirals with low rates of viral resistance) for HBsAg-positive/anti-HBc–positive patients (without delaying cancer therapy) and continue the antivirals during and for ~6 to 12 months after completing treatment. HBsAg-negative/anti-HBc–positive patients should be monitored for HBV reactivation with HBV DNA and ALT testing approximately every 3 months during treatment; antiviral therapy may be initiated prophylactically or begun promptly at the first sign of HBV reactivation.

• Infection: Bacterial, fungal, and new or reactivated viral infections may occur during and/or following therapy; fatal infections have been reported. Do not administer to patients with an active infection. Patients with a history of recurrent or chronic infections may be at increased risk; monitor closely for signs/symptoms of infection.

• Infusion reaction: May cause severe and life-threatening infusion reactions; reactions may include bronchospasm, dyspnea, tachycardia, larynx and throat irritation, wheezing, laryngeal edema, flushing, hypertension, hypotension, fever, dizziness, nausea, vomiting, diarrhea, headache, fatigue, and/or chills. Infusion reactions occur more frequently with the first 1,000 mg infused. Delayed reactions (up to 24 hours later) and reactions with subsequent infusions have occurred. Premedicate with acetaminophen, an antihistamine, and an IV glucocorticoid (dexamethasone or methylprednisolone) prior to infusion. Hydrocortisone has not been effective in reducing the rate of infusion reactions and is not recommended. Infusion reactions may require rate reduction, interruption of therapy, or treatment discontinuation. Monitor during the entire infusion; monitor patients with pre-existing cardiac or pulmonary conditions closely. Consider temporarily withholding antihypertensive therapies for 12 hours prior to, during, and for 1 hour after administration. Administer in a facility with immediate access to resuscitative measures (eg, glucocorticoids, epinephrine, bronchodilators, and/or oxygen).

• Progressive multifocal leukoencephalopathy: [US Boxed Warning]: Progressive multifocal leukoencephalopathy (PML) resulting in death may occur with treatment. PML is due to JC virus infection. Consider PML in any patient with new onset or worsening neurological symptoms and if PML is suspected, discontinue obinutuzumab (consider discontinuation or dose reduction of any concomitant chemotherapy or immunosuppressive therapy) and evaluate promptly.

• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been reported with obinutuzumab (some cases fatal). Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia may occur. Administer prophylaxis (antihyperuricemic therapy [eg, allopurinol or rasburicase] and hydration) in patients at high risk (high circulating lymphocyte counts [>25,000/mm3], high tumor burden, or renal impairment) prior to initiating obinutuzumab therapy (administer prior to each subsequent cycle if needed). Monitor lab parameters during initial treatment days in patients at risk for TLS. Correct electrolyte abnormalities; monitor renal function and hydration status, and administer supportive care, including dialysis as indicated.

Concurrent drug therapy issues:

• Antihypertensives: Due to the risk for hypotension, consider temporarily withholding antihypertensive therapies for 12 hours prior to, during, and for 1 hour after administration.

• Antiplatelet/anticoagulant medications: Due to the risk for thrombocytopenia and hemorrhagic events (particularly during the first cycle), consider withholding anticoagulants, platelet inhibitors, or other medications which may increase bleeding risk.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Immunizations: Administration of live virus vaccines during treatment (and until B-cell recovery) is not recommended; the safety and efficacy of immunization with live or attenuated viral vaccines during or after obinutuzumab therapy has not been determined. If obinutuzumab exposure occurs during pregnancy, the safety and timing of live virus vaccinations for the infant should be evaluated.

For the Consumer

Applies to obinutuzumab: intravenous solution

Along with its needed effects, obinutuzumab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking obinutuzumab:

More common
  • Back pain
  • black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • chest tightness
  • chills
  • cough or hoarseness
  • fever
  • flushing
  • headache
  • lower back or side pain
  • nausea and vomiting
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • sore throat
  • trouble breathing
  • troubled breathing with exertion
  • ulcers, sores, or white spots in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Less common
  • Joint pain, stiffness, or swelling
  • lower back, side, or stomach pain
  • swelling of the feet or lower legs
Incidence not known
  • Blurred vision
  • confusion
  • convulsions
  • dark urine
  • dizziness
  • drowsiness
  • general tiredness and weakness
  • headache
  • light-colored stools
  • upper right abdominal or stomach pain
  • yellow eyes and skin

Some side effects of obinutuzumab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known
  • Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

Usual Adult Dose for Chronic Lymphocytic Leukemia

INITIAL CYCLE (loading doses): 100 mg IV on Day 1, 900 mg IV on Day 2, then 1000 mg IV on Day 8 and Day 15
-If appropriate, patients who do not complete the Initial Cycle, Day 1 dose may proceed to the Initial Cycle, Day 2 dose.
SUBSEQUENT CYCLES: 1000 mg IV on Day 1 of each subsequent 28 day cycle
-If a planned dose is missed, administer the missed dose as soon as possible and adjust dosing schedule accordingly.
-DURATION OF THERAPY: This drug is administered for 6 treatment cycles of 28 days each

PREMEDICATION TO PREVENT INFUSION RELATED REACTIONS (IRR):
-CYCLE 1 (CLL Days 1 and 2): All patients should receive acetaminophen (650 to 1000 mg) AND an antihistamine (e.g., diphenhydramine 50 mg) at least 30 minutes prior to infusion AND an IV glucocorticoid (dexamethasone 20 mg or methylprednisolone 80 mg) at least 1 hour prior to infusion.
-ALL SUBSEQUENT INFUSIONS: All patients should receive acetaminophen (650 to 1000 mg) at least 30 minutes prior to infusion.
-If patients experienced Grade 1 or 2 IRR with the previous infusion: Administer an antihistamine (e.g., diphenhydramine 50 mg) in addition to acetaminophen (650 to 1000 mg) at least 30 minutes prior to infusion.
-If patients experienced Grade 3 IRR with the previous infusion OR have a lymphocyte count greater than 25 X 10(9)/L prior to next treatment: Administer an IV glucocorticoid (dexamethasone 20 mg or methylprednisolone 80 mg) at least 1 hour prior to infusion, in addition to acetaminophen (650 to 1000 mg) and an antihistamine (e.g., diphenhydramine 50 mg) at least 30 minutes prior to infusion.

RATE OF ADMINISTRATION:
-Cycle 1, Day 1 (100 mg): Infuse at 25 mg/hr IV over 4 hours; do not increase the rate
-Cycle 1, Day 2 (900 mg): Infuse at an initial rate of 50 mg/hr; the rate may be increased in increments of 50 mg/hr every 30 minutes to a maximum rate of 400 mg/hr
-Cycle 1, Day 8 (1000 mg) and Day 15 (1000 mg) and Cycles 2 through 6 (1000 mg each): If no infusion reaction occurred during the previous infusion and the final 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 rate of 400 mg/hr

Comments:
-Administration should be by a healthcare professional with appropriate medical support to manage severe infusion reactions that can be fatal if they occur.
-Premedicate before each infusion to reduce infusion related reactions.
-Do not administer as an IV push or bolus.
-Patients with high tumor burden, high circulating absolute lymphocyte counts (greater than 25 x 10(9)/L) or renal impairment are considered at risk of tumor lysis syndrome and should receive prophylaxis. Premedicate with antihyperuricemics (e.g., allopurinol, rasburicase) and ensure adequate hydration prior to start of therapy. Continue prophylaxis prior to each subsequent infusion, as needed.
-Hypotension may occur during the IV infusion. The clinician may consider withholding antihypertensive treatments for 12 hours prior to and throughout each infusion and for the first hour after administration.
-Monitor blood counts at regular intervals.
-Patients with Grade 3 to 4 neutropenia lasting more than one week should receive antimicrobial prophylaxis until resolution of neutropenia to Grade 1 or 2. -Antiviral and antifungal prophylaxis should be considered.
-Treatment interruption should be considered if patients experience an infection, Grade 3 or 4 cytopenia, or a Grade 2 or greater nonhematologic toxicity.

Use: The treatment of patients with previously untreated chronic lymphocytic leukemia, in combination with chlorambucil

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