Gazyva Injection 1000 mg/40 ml

Uses

Gazyva Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml in combination with chlorambucil is used for the treatment of patients with previously untreated chronic lymphocytic leukemia.

Follicular Lymphoma (FL): Gazyva Injection 1000 mg/40 ml in combination with chemotherapy, followed by Gazyva Injection 1000 mg/40 ml maintenance is used for the treatment of patients with previously untreated follicular lymphoma. Gazyva Injection 1000 mg/40 ml in combination with bendamustine, followed by Gazyva Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml is also used to associated treatment for these conditions: Refractory Follicular Lymphoma, Previously untreated Chronic lymphocytic leukemia

How Gazyva Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml with bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), FC (fludarabine, cyclophosphamide) and chlorambucil. Co administration with Gazyva Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml. 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 Injection 1000 mg/40 ml 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

Gazyva Injection 1000 mg/40 ml Disease Interaction

Major: Anti-CD20 antibodies – hepatitis B, Anti-CD20 antibodies – infections, tumor lysis syndromeModerate: cardiopulmonary disease, cytopenias

Volume of Distribution

Gazyva Injection 1000 mg/40 ml has a volume of distribution of about 3.8 L.

Elimination Route

Gazyva Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml and any potential adverse effects on the breastfed child from Gazyva Injection 1000 mg/40 ml or from the underlying maternal condition.

Contraindication

Gazyva Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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 Injection 1000 mg/40 ml 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.

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