obinutuzumab

(redirected from Gazyva)

obinutuzumab

(oh-bi-nue-tooz-ue mab ) ,

Gazyva

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: monoclonal antibodies
Pregnancy Category: C

Indications

Treatment-naïve patients with chronic lymphocytic leukemia (in combination with chlorambucil).

Action

Humanized anti-CD20 monoclonal IgG1 antibody, targeting an antigen found on the surface of pre and mature B- lymphocytes. Result is B-cell lysis and depletion.

Therapeutic effects

Decreased progression of chronic lymphocytic leukemia.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Unknown
Half-life: 28.4 days.

Time/action profile (improvement progression-free survival)

ROUTEONSETPEAKDURATION
IVwithin 3 mo12 mounknown

Contraindications/Precautions

Contraindicated in: Prior or concurrent live virus vaccinations; Lactation: Breast feeding should be avoided.
Use Cautiously in: Hepatitis B infection (may reactivate); Obstetric: Use only in pregnancy if potential benefit outweighs fetal risks; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • progressive multifocal leukoencephalopathy (life-threatening)

Respiratory

  • cough

Cardiovascular

  • hypotension

Gastrointestinal

  • hypocalcemia
  • hypokalmiea
  • hyponatremia

Hematologic

  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)
  • anemia

Musculoskeletal

  • musculoskeletal disorder

Miscellaneous

  • infusion reactions (life-threatening)
  • tumor lysis syndrome (life-threatening)
  • hepatitis B reactivation
  • fever

Interactions

Drug-Drug interaction

↑ risk of immunosuppression/neutropenia with other antineoplastics, immunosuppressants or radiation therapy.May ↓ antibody response to and ↑ risk of adverse reactions from live virus vaccines (do not administer prior to or during treatment).

Route/Dosage

Pre-medication is required
Intravenous (Adults) Day 1 of Cycle 1—100 mg, Day 2 of Cycle 1—900 mg, Days 8 and 15 of Cycle 1—1000 mg, Day 1 of Cycles 2–61000 mg. In the case of serious reactions/toxicity, treatment modification may be necessary.

Availability

Solution for IV administration (requires dilution): 1000 mg/40 mL vial (25 mg/mL)

Nursing implications

Nursing assessment

  • Monitor patient with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following therapy.
  • Monitor for signs of progressive multifocal leukoencephlopathy (PML) (new onset or changes in pre-existing neurological signs and symptoms). Initiate evaluation for PML (neurological consultation, brain MRI, lumbar puncture) if signs occur. Discontinue obinutuzumab if PML is suspected.
  • Assess for infusion-related reactions (hypotnesion, tachycardia, dyspnea, bronchospasm, larynx and throat irritation, wheezing, laryngeal edema, nausea, vomiting, diarrhea, hypertension, flushing, headache, pyrexia, chills) closely, especially during first 24 hrs. Premedicate and treat symptoms (glucorticoids, epinephrine, bronchodilators, oxygen).
  • Monitor patient for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia). Risks are higher in patients with greater tumor burden and rapidly proliferating tumors; may be fatal. Correct electrolyte abnormalities, hydrate patient, administer antihyperuricemic agents, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
  • Lab Test Considerations: Screen all patients for Hepatis B virus (HBV) infection. For patients with evidence of hepatitis B infection (HBsAg positive or HBsAg negative but anti-HBc positive consult health care professional with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy.
    • Monitor CBC frequently during therapy. May cause neutropenia; monitor for infection. Neutropenia may occur late onset, more than 28 days after completion of therapy and may be prolonged, lasting longer than 28 days.
    • Monitor platelet count frequently during therapy. May cause thrombocytopenia. May occur within 24 hr of infusion. May require platelet transfusion.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Administration should be limited to health care professionals and facilities able to manage severe infusion reactions.
  • Premedicate patients with a high tumor burden and/or high circulating absolute lymphocyte counts (>25 x 109/L) with anti-hyperuricemics (allopurinol) beginning 12–24 hrs before starting therapy. Ensure adequate hudration for prophylaxis of tumor lysis syndrome.
    • May cause hypotension. May require withholding antihypertensives for 12 hrs prior to and during each infusion and for first hr after infusion.
    • Premedicate patients with neutropenia with antimicrobial prophylaxis and consider antiviral and antifungal prophylaxis. Consider interrupting therapy if infection, Grade 3 or 4 cytopenia, or a ≥Grade 2 non-hematologic toxicity occurs.
    • Premedication Guidelines:Cycle 1: Day 1 and 2: Premedicate all patients with glucocorticoids IV: dexamethasone 20 mg or methylprednisolone 80 mg completed 1 hr prior to obinutuzumab infusion. Acetaminophen 650–1000 mg and antihistamine (diphenhydramine 50 mg) at least 30 min prior to infusion. Cycle 1: Day 8 and 15 and Cycle 2–6 Day 1: Premedicate all patients with acetaminophen 650–1000 mg at least 30 min before obinutuzumab infusion. Premedicate patients with ≥Grade 1 infusion reaction with previous infusion with antihistamine (diphenhydramine 50 mg) at least 30 min prior to infusion. Premedicate patients with a Gread 3 infusion-related reaction with previous infusion OR with a lymphocyte count >25 x 109/L prior to next treatmemt with glucocorticoids IV: dexamethasone 20 mg or methylprednisolone 80 mg completed 1 hr prior to obinutuzumab infusion.
  • Intravenous Administration
  • Intermittent Infusion: Diluent: Dilute into 0.9% NaCl PVC or non-OVC polyolefin infusion bag. Do not use other diluents.
    • Day 1 (100 mg) and Day 2 (900 mg) of Cycle 1:Withdraw 40 mL of obinutuzumab from vial. Dilute 4 mL (100 mg) into 100 mL of 0.9% NaCl infusion bag for immediate administration. Dilute remaining 36 mL (900 mg) into 250 mL of 0.9% NaCl infusion bag at same time for use on Day 2. Store in refrigerator for up to 24 hr. Infuse immediately after allowing bag to come to room temperature.
    • Day 8 and 15 of Cycle 1 and Day 1 Cycles 2–6: Withdraw 40 mL of obinutuzumab from vial. Dilute 40 mL (1000 mg) into 250 mL of 0.9% NaCl. Gently invert to mix; do not shake or freeze. If not administered immediately, stable in refrigerator for up to 24 hrs. Concentration: 0.4 mg/mL to 4 mg/mL.
  • Rate: Do not administer via IV push or bolus. Day 1; Cycle 1: Infuse at 25 mg/hr over 4 hrs. Day 2; Cycle 1: Infuse at 50 mg/hr. Increase infusion rate in increments of 50 mg/hr every 30 min to a maximum of 400 mg/hr. Do not increase infusion rate. Day 8 and 15; Cycle 1 and Day 1; Cycles 2–6: Infuse at 100 mg/hr and increase rate in 100 mg/hr increments every 30 min to a maximum of 400 mg/hr.
    • If infusion reaction occurs adjust rate as follows: Grade 1–2 (mild to moderate): Reduce or interrupt rate and treat symptoms. Continue or resume infusion upon resolution of symptoms. If no further infusion reaction symptoms, rate increase may resume as planned. Grade 3 (severe): Interrupt infusion and manage symptoms. Consider restarting infusion at one-half previous rate at time of interruption. If no further infusion reaction symptoms, rate increase may resume as planned. Permanently discontinue if Grade 3 infusion reaction symptoms occur at re-challenge. Grade 4 (life-threatening): Stop infusion immediately and permanently discontinue.
  • Y-Site Incompatibility: Infuse through a dedicated line.
  • Additive Incompatibility: Do not mix with other drugs.

Patient/Family Teaching

  • Inform patient of purpose of obinutuzumab.
  • Advise patient to avoid live viral vaccines during therapy
  • Instruct patient to notify health care professional immediately if signs and symptoms of infusion reaction (dizziness, nausea, chills, fever, vomiting, diarrhea, breathing problems, chest pain), tumor lysis syndrome (nausea, vomiting, diarrhea, lethargy), infection (fever, cough), hepatitis (worsening fatigue, yellow discoloration of skin or eyes) or new changes in neurological symptoms (confusion, dizziness, loss of balance, difficulty talking or walking, vision problems) occur.
  • Caution female patient to use effective contraception during and for at least 12 months following therapy and to avoid breastfeeding. Advise patient to notify health care professional immediately if pregnancy occurs.

Evaluation/Desired Outcomes

  • Decrease in progression of chronic lymphocytic leukemia.
References in periodicals archive ?
Biogen Idec - Growth from Newly Launched Products + Clinical Milestones of Novel Pipeline - Near-Term Key Pipeline Candidates to Watch - Hemophilia Franchise Offers Long-Term Opportunity - Anti-CD20 franchise Continues to Grow through Label Expansion of GAZYVA - NEUROLOGY: LEADERSHIP IN MS AND PORTFOLIO EXPANSION 5.
This is the ultimate raison d'etre to own Roche (and Gilead) since Gazyva will replace the blockbuster but mature Rituxan as the gold standard for blood cancer treatment.
Gazyva was discovered by Roche Innovation Center Zurich, formerly Roche Glycart AG, a wholly owned, independent research unit of Roche.
Prior to Igenica, he was a Senior Medical Director in the Exploratory Clinical Development (BioOncology) group at Genentech, where he spent seven years leading the clinical development of multiple small molecule, antibody and antibody-drug conjugate programs at stages ranging from IND filing to Phase 3, including clinical development of Gazyva (obinutuzumab).
Beleodaq -- Zykadia -- Cyramza -- Imbruvica -- Gazyva.
The other three drugs approved to treat CLL that received breakthrough designations are Gazyva (obinutuzumab) in November 2013, Arzerra (ofatumumab) in April 2014 and Zydelig (idelalisib) in July 2014.
Adcetris -- Kadcyla -- Gazyva -- Tresiba -- Afrezza -- Plegridy -- Eloctate.
Gazyva was approved in November 2013 in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia.
versus chlorambucil in combination with GAZYVA in newly diagnosed CLL/SLL patients was initiated in the fourth quarter of 2014.
Our study forecasts revenues of six products: -- Adcetris -- Kadcyla -- Poteligeo -- Gazyva -- Removab -- Kalbitor.
The FDA approved Gazyva (obinutuzumab) in November 2013, Imbruvica (ibrutinib) in February 2014 and a new use for Arzerra (ofatumumab) in April 2014 to treat CLL.