Drug Interaction:
No formal drug interaction studies have been conducted with GAZYVA.
Indication:
GAZYVA (obinutuzumab) Injection, for intravenous infusion
Initial U.S. Approval: 2013
WARNING: HEPATITIS B VIRUS REACTIVATION AND
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
See full prescribing information for complete boxed warning.
Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis,
hepatic failure, and death.
Progressive Multifocal Leukoencephalopathy (PML) resulting in death.
Drug Name- Gazyva
Active Ingredient - Obinutuzumab
For use in combination with chlorambucil to treat patients with previously
untreated chronic lymphocytic leukemia (CLL)
Indication-
Chronic Lymphocytic leukemia (CLL)
Approved by FDA on 01-11--2013 (Ref- FDA approved List- 2013)
Proprietary Name- GAZYVA INJECTION*
Established Name- Obinutuzumab
Applicant- GENETECH INC.
Indication- For use in combination with Chlorambucil for the
treatment of patients with previously untreated
Chronic Lymphoma Leukemia (CLL)
Approval Date- November 1,2013
Approved by U.S.FDA (Ref- FDA approved List- 2013)
Adverse Reaction:
The most common adverse reactions (incidence .10%) were: infusion
reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, and
musculoskeletal disorder.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Infusion reactions: Premedicate patients with glucocorticoid, acetaminophen
and anti-histamine. Monitor patients closely during infusions.
Interrupt or discontinue infusion for reactions.
.
Tumor Lysis Syndrome: Anticipate tumor lysis syndrome; premedicate with
anti-hyperuricemics and adequate hydration especially for patients
with high tumor burden and/or high circulating lymphocyte count.
Correct electrolyte abnormalities, provide supportive care and monitor
renal function and fluid balance.
.
Neutropenia: Monitor for infection.
.
Thrombocytopenia: Monitor platelet counts and for bleeding. Management
of hemorrhage may require blood product support. (
.
Immunization: Do not administer live virus vaccines prior to or during GAZYVA.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and is
indicated, in combination with chlorambucil, for the treatment of patients
with previously untreated chronic lymphocytic leukemia.
DOSAGE AND ADMINISTRATION
Premedicate with glucocorticoid, acetaminophen and anti-histamine.
Dilute and administer as intravenous infusion. Do not administer as an
intravenous push or bolus.
Recommended dose for 6 cycles (28 day cycles):
100 mg on day 1 Cycle 1
900 mg on day 2 Cycle 1
1000 mg on day 8 and 15 of Cycle 1
1000 mg on day 1 of Cycles 2-6
DOSAGE FORMS AND STRENGTHS
1000 mg/40mL (25 mg/mL) single use vial.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise patients to seek immediate medical attention for any of the following:
Signs and symptoms of infusion reactions including dizziness, nausea, chills, fever,
vomiting, diarrhea, breathing problems, or chest pain
Symptoms of tumor lysis syndrome such as nausea, vomiting, diarrhea and lethargy
Signs of infections including fever and cough.
Symptoms of hepatitis including worsening fatigue or yellow discoloration of skin
or eyes
New or changes in neurological symptoms such as confusion, dizziness or loss
of balance, difficulty talking or walking, or vision problems
Advise patients of the need for:
Periodic monitoring of blood counts
Avoid vaccinations with live viral vaccines
Patients with a history of hepatitis B infection (based on the blood test)
should be monitored and sometimes treated for their hepatitis .
:
Genentech, Inc.
A Member of the Roche Group
South San Francisco, CA 94080-4990
U.S. License No: 1048 GAZYVA is a trademark of Genentech, Inc.© 2013
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
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) by directly activating intracellular death signaling pathways and/or
(3) activation of the complement cascade.
2. Pharmacokinetics
Based on a population pharmacokinetic (pop-PK) analysis, the geometric mean
(CV%) volume of distribution of obinutuzumab at steady state is approximately 3.8 (23) L.
The elimination of obinutuzumab is comprised of a linear clearance pathway and
a time-dependent non-linear clearance pathway. As GAZYVA treatment progresses,
the impact of the time-dependent pathway diminishes in a manner suggesting
target mediated drug disposition
(TMDD). Based on a pop-PK analysis, the geometric mean (CV%) terminal
obinutuzumab clearance and half-life are approximately 0.09 (46%) L/day
and 28.4 (43%) days, respectively.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies of GAZYVA in pregnant women.
Women of childbearing potential should use effective contraception while receiving
GAZYVA and for 12 months following treatment. GAZYVA should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus.
2. Nursing Mothers
It is not known whether obinutuzumab is excreted in human milk. However,
obinutuzumab is excreted in the milk of lactating cynomolgus monkeys and
human IgG is known to be excreted in human milk. Because many drugs are excreted
in human milk and because of the potential for serious adverse reactions
in nursing infants from GAZYVA, a decision should be made whether to
discontinue nursing, or discontinue drug, taking into account the importance
of the drug to the mother
.
3.Pediatric Use
The safety and effectiveness of GAZYVA in pediatric patients has not been
established.
4. Geriatric Use
Of 240 previously untreated CLL patients who received GAZYVA in combination
with chlorambucil, 196 patients (82%) were . 65 years of age and 109 patients
(45%) were . 75 years of age. The median age was 74 years.
No significant differences in efficacy were observed between patients .75 years
of age and those <75 years of age
Manufacturer Details