Obinutuzumab


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV Chronic lymphocytic leukaemia In combination with chlorambucil in 6 28-day cycles: CYCLE 1: Day 1: 100 mg at 25 mg/hour over 4 hours; Day 2: 900 mg at 25-400 mg/hour; Days 8 and 15: 1,000 mg at 50-400 mg/hour. CYCLE 2-6: Day 1: 1,000 mg at 50-400 mg/hour. In case of toxicity, modify dose according to product literature. Follicular lymphoma Induction in combination with chemotherapy in either 6 21/28-day cycles or 8 21-day cycles: 1,000 mg on Cycle 1, Days 1, 8 and 15 and on Cycles 2-6/8, Day 1 at 50-400 mg/hour. Maintenance as monotherapy initiated approx 2 months after last induction dose: 1,000 mg every 2 months for 2 years or until disease progression. In case of toxicity, modify dose according to product literature. Refractory or relapsed follicular lymphoma Induction in combination with bendamustine in 6 28-day cycles: 1,000 mg on Cycle 1, Days 1, 8 and 15 and on Cycles 2-6, Day 1 at 50-400 mg/hour. Maintenance as monotherapy initiated approx 2 months after last induction dose: 1,000 mg every 2 months for 2 years or until disease progression. In case of toxicity, modify dose according to product literature.
Dosage Details
Intravenous
Chronic lymphocytic leukaemia
Adult: In combination with chlorambucil in 6 28-day cycles: CYCLE 1: Day 1: 100 mg at 25 mg/hour over 4 hours; Day 2: 900 mg at 25-50 mg/hour, increased by 50 mg/hour every 30 minutes to a max rate of 400 mg/hour; Days 8 and 15: 1,000 mg at 50-100 mg/hour, increased by 50-100 mg/hour every 30 minutes to a max rate of 400 mg/hour. CYCLE 2-6: Day 1: 1,000 mg at 50-100 mg/hour, increased by 50-100 mg/hour every 30 minutes to a max rate of 400 mg/hour. In case of toxicity, modify dose according to product literature. Pre-medicate with IV corticosteroid, oral analgesic (e.g. acetaminophen)/antipyretics and antihistamine.

Intravenous
Follicular lymphoma
Adult: Induction in combination with chemotherapy in either 6 21/28-day cycles or 8 21-day cycles: 1,000 mg on Cycle 1, Days 1, 8 and 15 and on Cycles 2-6/8, Day 1 at 50-100 mg/hour, increased by 50-100 mg/hour to a max rate of 400 mg/hour. Maintenance as monotherapy initiated approx 2 months after last induction dose: 1,000 mg every 2 months for 2 years or until disease progression. In case of toxicity, modify dose according to product literature. Pre-medicate with IV corticosteroid, oral analgesic (e.g. acetaminophen)/antipyretics and antihistamine.

Intravenous
Refractory follicular lymphoma, Relapsed follicular lymphoma
Adult: Induction in combination with bendamustine in 6 28-day cycles: 1,000 mg on Cycle 1, Days 1, 8 and 15 and on Cycles 2-6, Day 1 at 50-100 mg/hour, increased by 50-100 mg/hour to a max rate of 400 mg/hour. Maintenance as monotherapy initiated approx 2 months after last induction dose: 1,000 mg every 2 months for 2 years or until disease progression. In case of toxicity, modify dose according to product literature. Pre-medicate with IV corticosteroid, oral analgesic (e.g. acetaminophen)/antipyretics and antihistamine.
Reconstitution
Reconstitute 100 mg, 900 mg and 1000 mg vial with 4 mL, 36 mL and 40 mL respectively. To prepare the solution for infusion, further dilute with 100 mL (100 mg), 250 mL (900 mg) and 250 mL (1000 mg) NaCl 0.9% in polyvinyl chloride (PVC) or non-PVC polyolefin infusion bags. Mix gently. Do not shake.
Contraindications
Hypersensitivity to this drug including serum sickness. Administration of live viral vaccines.
Special Precautions
Patient with history or current serious infection especially hepatitis B virus (HBV) infection, risk of tumour lysis syndrome (e.g. high tumour burden, high lymphocyte count), cardiac and respiratory impairment. Renal impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Hypersensitivity reactions including serum sickness, hypotension.
Blood and lymphatic system disorders: Anaemia, leukopenia, lymphopenia, lymph node pain.
Cardiac disorders: Chest pain, atrial fibrillation, cardiac failure.
Gastrointestinal disorders: Nausea, diarrhoea, constipation, dyspepsia.
General disorders and administration site conditions: Fatigue, asthenia, pyrexia.
Infections and infestations: Herpes zoster and herpes simplex virus infection, sepsis.
Investigations: Increased AST/ALT, increased serum creatinine.
Metabolism and nutrition disorders: Hyper-/hypo-kalaemia, hyponatraemia, hypocalcaemia, hyperuricaemia, hypoalbuminemia, hypophosphatemia.
Musculoskeletal and connective tissue disorders: Extremities, back and bone pain; arthralgia.
Nervous system disorders: Headache.
Psychiatric disorders: Insomnia, anxiety, depression.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Cough, nasal congestion, rhinorrhoea, oropharyngeal pain, rhinitis, sinusitis, pharyngitis, influenza, nasopharyngitis, upper respiratory tract infection, lung infection, pneumonia.
Skin and subcutaneous tissue disorders: Alopecia, pruritus, eczema.
Vascular disorders: Hypertension.
Potentially Fatal: Serious bacterial, fungal, and viral infections, HBV reactivation leading to fulminant hepatitis and hepatic failure, tumour lysis syndrome, infusion related reactions, neutropenia, thrombocytopenia, haemorrhage. Rarely, PML.
MonitoringParameters
Monitor CBC with differential, renal function, electrolytes, uric acid level (if at risk for tumour lysis syndrome). Screen for HBV infection with hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) levels (prior to therapy). Evaluate fluid status. Monitor for signs and symptoms of active HBV infection, progressive multifocal leukoencephalopathy (PML) with brain MRI and lumbar puncture, infusion related reactions.
Drug Interactions
May increase risk of hypotension with antihypertensive agents. May increase risk of haemorrhage with anticoagulants, platelet inhibitors.
Potentially Fatal: May enhance the adverse effects and diminish the therapeutic effects of live vaccines.
Action
Description: Obinutuzumab, an antineoplastic drug, is a type II anti-CD20 and recombinant humanised monoclonal antibody. Following binding to CD20, this drug causes lysis of B lymphocytes by inducing direct cell death and by mediating antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). It also mediates complement dependent cytotoxicity.
Pharmacokinetics:
Distribution: Distributed mainly in the interstitial fluid. Crosses the placenta. Volume of distribution: Approx 4.1-4.3 L.
Excretion: Elimination half-life: 25.5-35.3 days.
Storage
Store between 2-8°C. Protect from light.
Any unused portions should be disposed of in accordance with local requirements.
ATC Classification
L01XC15 - obinutuzumab ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Obinutuzumab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/01/2018.

Buckingham R (ed). Obinutuzumab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com/. Accessed 03/01/2018.

Gazyva Injection, Solution, Concentrate (Genentech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/01/2018.

Joint Formulary Committee. Obinutuzumab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/01/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Obinutuzumab. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 03/01/2018.

Disclaimer: This information is independently developed by MIMS based on Obinutuzumab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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