Generic
Obinutuzumab
1 brands available in the market
At a glance
Obinutuzumab is a CD20-directed cytolytic monoclonal antibody used for chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). It binds to CD20 antigen on B-cells to mediate B-cell lysis.
Description
Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B lymphocytes. Upon binding to CD20, obinutuzumab mediates B-cell lysis through (1) engagement of immune effector cells, (2) direct activation of intracellular death signaling pathways, and/or (3) activation of the complement cascade.
Indications
- Previously untreated chronic lymphocytic leukemia (with chlorambucil)
- Previously untreated follicular lymphoma (with chemotherapy + maintenance)
- Refractory or relapsed follicular lymphoma (with bendamustine + maintenance)
Therapeutic class
Anti-neoplastic Preparations
Pharmacological class
CD20-directed Cytolytic Antibody
Pharmacology
Obinutuzumab binds to CD20 antigen to mediate B-cell lysis through immune effector cells (ADCC, ADCP), direct apoptosis, and complement-dependent cytotoxicity (CDC).
Mechanism of action
Destroys cancer cells by targeting CD20 antigen on B-cells.
Dosage
CLL (with Chlorambucil, 6 x 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 min to max 400 mg/hour; Days 8 & 15: 1,000 mg at 50-100 mg/hour, increased by 50-100 mg/hour every 30 min to max 400 mg/hour
- Cycles 2-6, Day 1: 1,000 mg at 50-100 mg/hour to max 400 mg/hour
FL (Induction + Maintenance): Induction: 1,000 mg on Cycle 1, Days 1,8,15 and Cycles 2-6/8, Day 1; Maintenance: 1,000 mg every 2 months for up to 2 years
Administration
- Administer as IV infusion only; do not give as IV push or bolus
- Dilute in 0.9% Sodium Chloride; do not use dextrose 5%
- Pre-medicate with IV corticosteroid, oral analgesic and antihistamine before administration
- Do not mix with other drugs
Missed dose
Not generally applicable (scheduled administration); consult doctor if needed.
Side effects
Common Side 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%)
Serious: Hepatitis B reactivation, PML, tumor lysis syndrome, infections
Precautions & warnings
- Caution in patients with history or current hepatitis B virus infection
- Risk of tumor lysis syndrome (high tumor burden, high lymphocyte count)
- Cardiac and respiratory impairment
- Caution in renal impairment
- Avoid live viral vaccines
- Caution during pregnancy and lactation
Contraindications
- Hypersensitivity
- Administration of live viral vaccines
Drug interactions
- May increase risk of hypotension with antihypertensive agents
- May increase risk of hemorrhage with anticoagulants, platelet inhibitors
- May enhance adverse effects and diminish therapeutic effects of live vaccines
Food interactions
No food interactions (IV administration).
Use in pregnancy
Use in Pregnancy: Obinutuzumab is highly unsafe during pregnancy; animal studies show fetal B-cell depletion; consider potential risk to fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: No information on presence in human milk; consider benefits and risks of breastfeeding.
Pediatric use
Safety and efficacy not established in children below 18 years.
Geriatric use
Patients ≥75 years in CLL had more serious adverse events; patients ≥65 years in NHL had more serious adverse events.
Renal / hepatic impairment
Renal Impairment: Caution in kidney disease; dose adjustment may be needed.
Hepatic Impairment: Caution in liver disease; dose adjustment may be needed.
Overdose effects
Limited information on overdose; symptomatic treatment.
Storage conditions
Store at 2-8°C in refrigerator; do not freeze; protect from light; do not shake.
Chemical structure
Obinutuzumab