Names and pronunciation
(oh′bi-nue-tooz′ue-mab) Gazyva
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Drug reference
(oh′bi-nue-tooz′ue-mab) Gazyva
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Func. class.: Antineoplastic; bio- logic response modifier; monoclonal antibody
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ACTION: A recombinant, human monoclonal antibody that binds to the gastric B-lymphocyte–associated anti- body; action is indirect, possible through T-cell–mediated anti-tumor responses
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USES: Chronic lymphocytic leukemia, previously untreated in combination with chlorambucil; non-Hodgkin’s lymphoma (follicular lymphoma) in relapse or refrac- tory to rituximab-containing regimen, used in combination; previously untreated stage II bulky, III, or IV follicular lymphoma in combination, then monotherapy
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CONTRAINDICATIONS: Hyper- sensitivity Precautions: Pregnancy, breastfeed- ing, cardiac disease, children, human antichimeric antibody (HACA), human antimurine antibody (HAMA), infection, infusion-related reactions, neutropenia, pulmonary disease, thrombocytopenia, tumor lysis syndrome, vaccination
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Black Box Warning: Hepatitis B exacer- bation, progressive multifocal leukoen- cephalopathy Black Box Warning: Hepatitis B: reacti- vation of HBV in those who are HBsAg pos- itive, HBsAg negative, and core antibody anti-HBc positive; may result in fulminant hepatitis, hepatic failure, or death, screen high-risk patients before use, monitor car- riers for active HBV infection during and for several months after therapy completion, discontinue treatment of any other anti- neoplastics if infection is reactivated Black Box Warning: Progressive mul- tifocal leukoencephalopathy (PML): notify prescriber of any new, worsening neurological signs/symptoms (ataxia, visual changes, confusion) • Tumor lysis syndrome: can occur within 24 hr of 1st infusion; those with high tumor burden or lymphocyte count >25 × 109/L are at increased risk; moni- tor serum creatinine, potassium, calcium, uric acid, phosphate closely • Severe/life-threatening infusion reac- tions: 2⁄3 have a reaction to 1st dose; consider withholding antihypertensives for 12 hr be- fore, during, and for 1 hour after infusion • Bone marrow suppression: CBC with differential before infusion and regularly, platelets • Infection: signs of infection; provide neutropenia precautions • Pregnancy/breastfeeding: use only if benefits outweigh fetal risk; do not breastfeed, excretion unknown Black Box Warning: Hepatitis B: to re- port yellow skin, eyes, fatigue, dark urine; that continuing follow-up will be needed Black Box Warning: Progressive mul- tifocal leukoencephalopathy (PML): to report confusion, visual changes, dizzi- ness, difficulty walking or talking
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SIDE EFFECTS CNS: Headache, fever, chills, flushing CV: Cardiac arrest, MI, sinus tachycardia, hypertension GI: Constipation, decreased appetite, diarrhea, hepatitis/hepatic failure, nau- sea, vomiting HEMA: Neutropenia, thrombocytopenia, lymphopenia, leukopenia, anemia META: Lower potassium/sodium/cal- cium, aluminum, higher potassium/uric acid RESP: Wheezing, dyspnea, cough SYST: Tumor lysis syndrome, infection O MISC: Arthralgia
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INTERACTIONS Increase: adverse reactions—abcix- imab, belimumab, cloZAPine, pimecroli- mus; avoid concurrent use Increase: infection—denosumab, natali- zumab, live virus vaccines Increase: hypotension—antihyperten- sives Increase: thrombocytopenia—chloram- bucil Increase: hematologic toxicity—leflu- nomide Increase: immunosuppression—tofaci- tinib; avoid concurrent use Drug/Herb Decrease: obinutuzumab—echinacea Drug/Lab
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DOSAGE AND ROUTES Chronic lymphocytic leukemia (previously untreated); in combina- tion with chlorambucil Adult: IV: Cycle 1: 100 mg on day 1, followed by 900 mg on day 2, followed by 1000 mg weekly for 2 doses (days 8 and 15); treatment cycle is 28 days; cycles 2 through 6: 1000 mg on day 1 every 28 days for 5 doses Follicular lymphoma (relapsed/ refractory) Adult: IV: Cycle 1 (in combination with bendamustine): 1000 mg weekly on days 1, 8, and 15; treatment cycle is 28 days; cycles 2 through 6 (in combina- tion with bendamustine): 1000 mg on day 1 every 28 days for 5 doses; obinutu- zumab monotherapy: 1000 mg every 2 mo for up to 2 yr
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Available forms: Sol for inj 1000 mg/40 mL (25 mg/mL)
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Administer: IV intermittent INFUSION route • Due to the risk of hypotension, consider withholding antihypertensive medications for 12 hr before, during, and for the 1st hr after use until blood pressure is stable • Single-use vials do not contain preser- vatives • Do not mix with other products • Give antimicrobial prophylaxis to neu- tropenic patients throughout treatment; consider antiviral and antifungal prophy- laxis as needed • Premedication for cycle 1, days 1 and 2: acetaminophen 650-1000 mg, and diphenhydrAMINE 50 mg at least 30 min before infusion, dexametha- sone 20 mg IV or methylPREDNISolone 80 mg IV at least 1 hr before infusion • Premedication for cycle 1, days 8 and 15, and cycles 2-6, day 1: acetamino- phen 650-1000 mg at least 30 min be- fore infusion; those with any infusion- related reaction with the previous infusion should also receive diphen- hydrAMINE 50 mg at least 30 min be- fore the infusion; if the patient had a grade 3 infusion-related reaction with the previous dose or has a lymphocyte count >25 × 109/L, additionally admin- ister dexamethasone 20 mg IV or meth- ylPREDNISolone 80 mg IV at least 1 hr before infusion • Use in a facility to adequately monitor and treat infusion reactions • Visually inspect parenteral products for particulate matter and discoloration before use • Prepare all doses in 0.9% NaCl; do not admix; use a final concentration of 0.4-4 mg/mL; give as an IV infusion only Reconstitution: Cycle 1, days 1 and 2: • Withdraw 4 mL (100 mg) from the vial and dilute into 100 mL 0.9% NaCl for use on day 1; mix by gentle inversion; do not shake, use immediately • Withdraw the remaining 36 mL (900 mg) and dilute into 250 mL 0.9% NaCl for use on day 2; mix by gentle inversion; do not shake Cycle 1, days 8 and 15; cycles 2-6: • Withdraw 40 mL (1000 mg) from the vial and dilute into 250 mL 0.9% NaCl; mix by gentle inversion; do not shake • Store following reconstitution: store at 2°C-8°C (36°F-46°F) for up to 24 hr; do not freeze; allow to come to room tem- perature before administration; use a dedicated line, protect from light • Day 1 (100-mg dose): give at initial rate of 25 mg/hr over 4 hr; do not in- crease the infusion rate • Day 2 (900-mg dose): give at 50 mg/ hr × 30 min; if no hypersensitivity or in- fusion-related events occur, increase the rate by 50 mg/hr q30min to a max rate of 400 mg/hr • Subsequent infusions (1000-mg dose): give at rate of 100 mg/hr for 30 min; if no hypersensitivity or infusion- related events occur, increase the infu- sion rate by 100 mg/hr q30min, max rate of 400 mg/hr
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Assess:
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Evaluate: • Therapeutic response: decreased dis- ease progression
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • About the reason for treatment and expected results • To avoid live virus vaccines, that vac- cinations should be brought up-to-date before treatment
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PHARMACOKINETICS Terminal half-life 29 days
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