Gazyva
Gazyva Uses, Dosage, Side Effects, Food Interaction and all others data.
Gazyva 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 lysisthrough (1) engagement of immune effector cells (2) by directly activating intracellular death signaling pathways (direct cell death), and/or (3) activation of the complement cascade. The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibodydependent cellular phagocytosis.
As an antibody with reduced fucose content, obinutuzumab induces greater ADCC activity than rituximab in vitro using human cancer cell lines. Gazyva also demonstrated an increased ability to induce direct cell death when compared to rituximab. Gazyva binds to FcγRIII using purified proteins with a higher affinity than rituximab. Gazyva and rituximab bind with similar affinity to overlapping epitopes on CD20.
Gazyva is more potent than rituximab in depleting B-cells, antitumor activity, and tumor regression.
| Trade Name | Gazyva |
| Availability | Prescription only |
| Generic | Obinutuzumab |
| Obinutuzumab Other Names | Afutuzumab, Obinutuzumab |
| Related Drugs | Calquence, Truxima, Gazyva, Zydelig, Tecartus, Venclexta, rituximab, Rituxan, Revlimid, cyclophosphamide |
| Weight | 1000mg/40ml, , 25mg/ml |
| Type | Solution For Infusion, Injection, Solution, Concentrate, Intravenous Solution |
| Formula | C6512H10060N1712O2020S44 |
| Weight | 146100.0 Da |
| Protein binding | Obinutuzumab does not bind to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | Anti neoplastic preparations |
| Manufacturer | Roche Limited, Roche Bangladesh Limited |
| Available Country | India, Bangladesh, Canada, Australia, Saudi Arabia, United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Gazyva is a clear, colorless to slightly brownish liquid supplied as a single 1000 mg dose in a sterile, preservative free, nonpyrogenic 50 ml glass vial containing 40 ml of liquid concentrate (25 mg/ml).
Chronic Lymphocytic Leukemia (CLL): Gazyva in combination with chlorambucil is used for the treatment of patients with previously untreated chronic lymphocytic leukemia.
Follicular Lymphoma (FL): Gazyva in combination with chemotherapy, followed by Gazyva maintenance is used for the treatment of patients with previously untreated follicular lymphoma. Gazyva in combination with bendamustine, followed by Gazyva maintenance, is used for the treatment of patients with FL who did not respond to, or who progressed during or after treatment with rituximab or a rituximab-containing regimen.
Gazyva is also used to associated treatment for these conditions: Refractory Follicular Lymphoma, Previously untreated Chronic lymphocytic leukemia
How Gazyva works
In contrast to rituximab, which is a classic type I CD20 antibody, obinutuzumab binds to type II CD20 antibodies. This allows obinutuzumab to have a much higher induction of antibody-dependant cytotoxicity and a higher direct cytotoxic effect than the classic CD20 antibodies.
Dosage
Gazyva dosage
Side Effects
The following adverse reactions are discussed in greater detail in other sections of the label:
- Hepatitis B reactivation
- Progressive multifocal leukoencephalopathy
- Infusion reactions
- Tumor lysis syndrome
- Infections
- Neutropenia
- Thrombocytopenia
Toxicity
The most serious toxicities observed with obinutuzumab are Hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML). HBV reactivation can occur with all anti-CD20 antibodies and can result in hepatic failure, fulminant hepatitis, and death. PML occurs as a result of JC virus infection and can be fatal as well. Other common but less serious adverse reactions include infusion reactions (pre-treat with glucocorticoids, acetaminophen, and anti-histamine to prevent this), neutropenia, thrombocytopenia, and Tumor Lysis Syndrome (TLS) (pre-treat patients, especially with a high lymphocyte count and/or a high tumor burden, with anti-hyperuricemics and hydration). It is also recommended to NOT administer live virus vaccinations prior to or during obinutuzumab treatment.
Precaution
In order to improve the traceability of biological medicinal products, the trade name and batch number of the administered product should be clearly recorded (or stated) in the patient file.
Interaction
No formal drug-drug interaction studies have been performed, although limited drug interaction sub-studies have been undertaken for Gazyva with bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), FC (fludarabine, cyclophosphamide) and chlorambucil. Co administration with Gazyva had no effect on the pharmacokinetics of bendamustine, FC or the individual components of CHOP; in addition, there were no apparent effects of bendamustine, FC, chlorambucil or CHOP on the pharmacokinetics of Gazyva. A risk for interactions with concomitantly used medicinal products cannot be excluded.
Food Interaction
- Avoid echinacea. Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.
Gazyva Drug Interaction
Unknown: charcoal, amphetamine / dextroamphetamine, fluticasone / salmeterol, contained in alcoholic beverages , naproxen, RHO Immunoglobulin , multivitamin with minerals, aspirin, aspirin, lorazepam, azithromycin, sulfamethoxazole / trimethoprim, rosuvastatin, escitalopram, acetaminophen / hydrocodone, acetaminophen, bioflavonoids, vitamin a topical, cyanocobalamin, cholecalciferol
Volume of Distribution
Gazyva has a volume of distribution of about 3.8 L.
Elimination Route
Gazyva is administered intravenously, so its absorption is 100%.
Half Life
The half life of obinutuzumab is 28.4 days.
Clearance
The clearance of obinutuzumab is 0.09L/day.
Elimination Route
The route of elimination of obinutuzumab was not indicated (FDA label).
Pregnancy & Breastfeeding use
Pregnancy: Gazyva is likely to cause fetal B-cell depletion based on findings from animal studies and the drug’s mechanism of action. There are no data with Gazyva use in pregnant women to inform a drug-associated risk. Monoclonal antibodies are transferred across the placenta. In animal reproduction studies, weekly intravenous administration of obinutuzumab to pregnant cynomolgus monkeys from day 20 of pregnancy until parturition which includes the period of organogenesis at doses with exposures up to 2.4 times the exposure at the clinical dose of 1000 mg monthly produced opportunistic infections and immune complex mediated hypersensitivity reactions. No embryo-toxic or teratogenic effects were observed in the monkeys. Consider the potential risk to the fetus when prescribing Gazyva to a pregnant woman.
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Lactation: There is no information regarding the presence of Gazyva in human milk, the effects on the breastfed child, or the effects on milk production. However, low levels of obinutuzumab were present in the milk of lactating cynomolgus monkeys [see Pregnancy]. Human IgG is known to be present in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and child circulations in substantial amounts. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Gazyva and any potential adverse effects on the breastfed child from Gazyva or from the underlying maternal condition.
Contraindication
Gazyva is contraindicated in patients with a known hypersensitivity to obinutuzumab or to any of the excipients.
Special Warning
Pediatric Use: The safety and efficacy of Gazyva in children below 18 years of age have not been established.Geriatric Use:
- Chronic Lymphocytic Leukemia (CLL): In the pivotal study in CLL, 46% (156 out of 336) of patients treated with Gazyva plus chlorambucil were 75 years old or older (median age was 74 years). These patients experienced more serious adverse events and adverse events leading to death than patients <75 years of age. No significant differences in efficacy were observed between patients ≥75 years of age and those <75 years of age
- Non-Hodgkin Lymphoma (NHL): In the pivotal studies in NHL, patients 65 years old or older experienced more serious adverse events, and adverse events leading to withdrawal or death than patients <65 years of age. No clinically meaningful differences in efficacy were observed.
Storage Condition
Store vials in a refrigerator at 2°C-8°C. Keep vial in the outer carton in order to protect from light. Do not freeze. Do not shake.
Innovators Monograph
You find simplified version here Gazyva
