Obinutuzumab

What is Obinutuzumab?

• Obinutuzumab (Gazyva) is a CD20-directed cytolytic antibody used to treat certain types of follicular lymphoma that have not already been treated.
• It is also used with bendamustine to treat follicular lymphoma that came back or has not gotten better after treatment with rituximab. Obinutuzumab is also used with chlorambucil to treat chronic lymphocytic leukemia (CLL).

What are the uses of this medicine?

This medicine is used:

• in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia.
• in combination with bendamustine followed by Gazyva monotherapy, for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen.
• in combination with chemotherapy followed by Gazyva monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III or IV follicular lymphoma.

How does this medicine work?

• 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 (direct cell death), and/or
• (3) activation of the complement cascade.
• The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis.
• As an antibody with reduced fucose content, obinutuzumab induces greater ADCC activity than rituximab in vitro using human cancer cell lines.
• Obinutuzumab also demonstrated an increased ability to induce direct cell death when compared to rituximab.
• Obinutuzumab binds to FcγRIII using purified proteins with a higher affinity than rituximab.
• Obinutuzumab and rituximab bind with similar affinity to overlapping epitopes on CD20.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• with known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or to any of the excipients, or serum sickness with prior obinutuzumab use.

What drug interactions can this medicine cause?

• No formal drug interaction studies have been conducted with Gazyva .

Is this medicine FDA approved?

• Initial U.S. Approval: 2013

How should this medicine be used?

• Premedicate for infusion-related reactions and tumor lysis syndrome.
• Provide prophylactic hydration and anti-hyperuricemics to patients at high risk of tumor lysis syndrome.

Recommended Dosage:

• The recommended dosage for chronic lymphocytic leukemia is 100 mg on day 1 and 900 mg on day 2 of Cycle 1, 1,000 mg on day 8 and 15 of Cycle 1, and 1,000 mg on day 1 of Cycles 2–6.
• The recommended dosage for follicular lymphoma is 1,000 mg on day 1, 8 and 15 of Cycle 1, 1,000 mg on day 1 of Cycles 2-6 or Cycles 2-8, and then 1,000 mg every 2 months for up to 2 years.

Administration

• Administer as an intravenous infusion only.
• Do not administer as an intravenous push or bolus.
• Do not mix Gazyva with other drugs.
• No incompatibilities between Gazyva and polyvinylchloride (PVC) or non-PVC polyolefin bags and administration sets have been observed.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 1,000 mg/40 mL (25 mg/mL) single-dose vial.

This medicine is available in fallowing brand namesː

• Gazyva

What side effects can this medication cause?

The most common side effects of this medicine include: Previously untreated CLL:

• infusion-related reactions
• neutropenia

Relapsed or refractory NHL:

• infusion-related reactions
• fatigue
• neutropenia
• cough
• upper respiratory tract infections
• musculoskeletal pain

Previously untreated NHL:

• infusion-related reactions
• neutropenia
• upper respiratory tract infections
• cough
• constipation
• diarrhea

What special precautions should I follow?

• Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with anti-CD20 antibodies such as Gazyva.
• John Cunningham (JC) virus infection resulting in progressive multifocal leukoencephalopathy (PML), which can be fatal, occurred in patients treated with Gazyva.
• Gazyva can cause severe and life-threatening infusion-related reactions (IRRs). Premedicate patients with glucocorticoid, acetaminophen, and anti-histamine. Monitor patients closely during infusions. Interrupt, reduce rate, or discontinue for infusion-related reactions based on severity.
• Hypersensitivity reactions have been reported in patients treated with Gazyva. If a hypersensitivity reaction is suspected during or after an infusion, stop the infusion and permanently discontinue treatment. Gazyva is contraindicated in patients with known hypersensitivity reactions to Gazyva, including serum sickness with prior obinutuzumab use
• Tumor lysis syndrome (TLS), including fatal cases, has been reported in patients receiving Gazyva. Premedicate with anti-hyperuricemics and adequate hydration, especially for patients with high tumor burden, high circulating lymphocyte count or renal impairment. Correct electrolyte abnormalities, provide supportive care, and monitor renal function and fluid balance.
• Do not administer Gazyva to patients with an active infection. Patients with a history of recurring or chronic infections may be at increased risk of infection.
• Severe and life-threatening neutropenia, including febrile neutropenia, has been reported during treatment with Gazyva. In patients with Grade 3 to 4 neutropenia, monitor laboratory tests until resolution and for infection. Consider dose delays and infection prophylaxis, as appropriate.
• Severe and life-threatening thrombocytopenia has been reported during treatment with Gazyva in combination with chemotherapy. Monitor platelet counts and for bleeding. Transfusion may be necessary.
• Avoid administration of live virus vaccines during Gazyva treatment and until B-cell recovery.
• Gazyva Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use effective contraception.

What to do in case of emergency/overdose?

• There has been no experience with overdose in human clinical trials.

Management of overdosage:

• For patients who experience overdose, treatment should consist of immediate interruption or reduction of Gazyva and supportive therapy.

Can this medicine be used in pregnancy?

• Based on findings from animal studies and its mechanism of action, Gazyva can cause fetal B-cell depletion.
• There are no data with Gazyva use in pregnant women to inform a drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of Gazyva in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active Ingredient:

• OBINUTUZUMAB

Inactive ingredients:

• HISTIDINE
• HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE
• TREHALOSE DIHYDRATE
• POLOXAMER 188
• WATER

Who manufactures and distributes this medicine?

• Manufactured by:

Genentech, Inc. A Member of the Roche Group South San Francisco

• Gazyva is a registered trademark of Genentech, Inc.

What should I know about storage and disposal of this medication?

• Store at 2°C to 8°C (36°F to 46°F).
• Do not use beyond expiration date stamped on carton.
• Protect from light.
• DO NOT FREEZE.
• DO NOT SHAKE.

• Dailymed label info on Obinutuzumab
• FDA Obinutuzumab

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