Indication GAZYVA ® ( obinutuzumab ), in combination with bendamustine followed by GAZYVA monotherapy , is indicated for the treatment of patients with follicular lymphoma ( FL ) who relapsed after , or are refractory to , a rituximab-containing regimen .
Boxed WARNINGS : HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
• Hepatitis B Virus ( HBV ) reactivation , in some cases resulting in fulminant hepatitis , hepatic failure , and death , can occur in patients receiving CD20-directed cytolytic antibodies , including GAZYVA . Screen all patients for HBV infection before treatment initiation . Monitor HBV positive patients during and after treatment with GAZYVA . Discontinue GAZYVA and concomitant medications in the event of HBV reactivation
• Progressive Multifocal Leukoencephalopathy ( PML ) including fatal PML , can occur in patients receiving GAZYVA
IMPORTANT SAFETY INFORMATION
Hepatitis B Virus Reactivation
• 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 including GAZYVA . HBV reactivation has been reported in patients who are hepatitis B surface antigen ( HBsAg ) positive and in patients who are HBsAg negative but are hepatitis B core antibody ( anti-HBc ) positive . Reactivation has also occurred in patients who appear to have resolved hepatitis B infection ( ie , HBsAg negative , anti-HBc positive , and hepatitis B surface antibody [ anti-HBs ] positive )
• HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level , or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive . Reactivation of HBV replication is often followed by hepatitis , ie , increase in transaminase levels and , in severe cases , increase in bilirubin levels , liver failure , and death
• Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with GAZYVA . For patients who show evidence of hepatitis B infection ( HBsAg positive [ regardless of antibody status ] or HBsAg negative but anti-HBc positive ), consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy
• Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment with GAZYVA
• In patients who develop reactivation of HBV while receiving GAZYVA , immediately discontinue GAZYVA and any concomitant chemotherapy and institute appropriate treatment . Resumption of GAZYVA in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing hepatitis B . Insufficient data exist regarding the safety of resuming GAZYVA in patients who develop HBV reactivation
Progressive Multifocal Leukoencephalopathy ( PML )
• JC virus infection resulting in PML , which can be fatal , was observed in patients treated with GAZYVA . Consider the diagnosis of PML in any patient presenting with new onset or changes to preexisting neurologic manifestations . Evaluation of PML includes , but is not limited to , consultation with a neurologist , brain MRI , and lumbar puncture . Discontinue GAZYVA therapy and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML
Infusion Reactions
• GAZYVA can cause severe and life-threatening infusion reactions . Thirty-eight percent of patients experienced a reaction on Day 1 during treatment with GAZYVA in combination with bendamustine . Infusion reactions can also occur with subsequent infusions . Symptoms may include hypotension , tachycardia , dyspnea , and respiratory symptoms ( eg , bronchospasm , larynx and throat irritation , wheezing , and laryngeal edema ). Most frequently reported symptoms include nausea , fatigue , dizziness , vomiting , diarrhea , hypertension , flushing , headache , pyrexia , and chills
• Premedicate patients with acetaminophen , an antihistamine , and a glucocorticoid . Institute medical management for infusion reactions as needed . Closely monitor patients during the entire infusion . Infusion reactions within 24 hours of receiving GAZYVA have occurred
• For patients with any Grade 4 infusion reactions , including but not limited to anaphylaxis , acute life-threatening respiratory symptoms , or other life-threatening infusion reaction : Stop the GAZYVA infusion . Permanently discontinue GAZYVA therapy
• For patients with Grade 1 , 2 , or 3 infusion reactions : Interrupt GAZYVA for Grade 3 reactions until resolution of symptoms . Interrupt or reduce the rate of the infusion for Grade 1 or 2 reactions and manage symptoms
• For patients with preexisting cardiac or pulmonary conditions , monitor more frequently throughout the infusion and the postinfusion period since they may be at greater risk of experiencing more severe reactions . Hypotension may occur as part of the GAZYVA infusion reaction . Consider withholding antihypertensive treatments for 12 hours prior to and during each GAZYVA infusion , and for the first hour after administration until blood pressure is stable . For patients at increased risk of hypertensive crisis , consider the benefits versus the risks of withholding their antihypertensive medication
Tumor Lysis Syndrome ( TLS )
• Tumor lysis syndrome , including fatal cases , has been reported in patients receiving GAZYVA . Patients with high tumor burden , high circulating lymphocyte count (> 25 x 10 9 / L ) or renal impairment are at greater risk for TLS and should receive appropriate tumor lysis prophylaxis with antihyperuricemics ( eg , allopurinol or rasburicase ) and hydration prior to the infusion of GAZYVA . During the initial days of GAZYVA treatment , monitor the laboratory parameters of patients considered at risk for TLS . For treatment of TLS , correct electrolyte abnormalities , monitor renal function and fluid balance , and administer supportive care , including dialysis as indicated
Please see the following pages for additional Important Safety Information and the brief summary of the full Prescribing Information , including Boxed WARNINGS .
Indication
GAZYVA® (obinutuzumab), in combination with bendamustine followed by GAZYVA monotherapy, is
indicated for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to,
a rituximab-containing regimen.
Boxed WARNINGS: HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY
• Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure,
•
and death, can occur in patients receiving CD20-directed cytolytic antibodies, including GAZYVA.
Screen all patients for HBV infection before treatment initiation. Monitor HBV positive patients
during and after treatment with GAZYVA. Discontinue GAZYVA and concomitant medications in
the event of HBV reactivation
Progressive Multifocal Leukoencephalopathy (PML) including fatal PML, can occur in patients
receiving GAZYVA
IMPORTANT SAFETY INFORMATION
Hepatitis B Virus Reactivation
• 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 including GAZYVA. HBV
reactivation has been reported in patients who are hepatitis B surface
antigen (HBsAg) positive and in patients who are HBsAg negative but
are hepatitis B core antibody (anti-HBc) positive. Reactivation has also
occurred in patients who appear to have resolved hepatitis B infection
(ie, HBsAg negative, anti-HBc positive, and hepatitis B surface
antibody [anti-HBs] positive)
• HBV reactivation is defined as an abrupt increase in HBV
replication manifesting as a rapid increase in serum HBV DNA
level, or detection of HBsAg in a person who was previously HBsAg
negative and anti-HBc positive. Reactivation of HBV replication is
often followed by hepatitis, ie, increase in transaminase levels and,
in severe cases, increase in bilirubin levels, liver failure, and death
• Screen all patients for HBV infection by measuring HBsAg and
anti-HBc before initiating treatment with GAZYVA. For patients
who show evidence of hepatitis B infection (HBsAg positive
[regardless of antibody status] or HBsAg negative but anti-HBc
positive), consult physicians with expertise in managing hepatitis B
regarding monitoring and consideration for HBV antiviral therapy
• Monitor patients with evidence of current or prior HBV infection for
clinical and laboratory signs of hepatitis or HBV reactivation during
and for several months following treatment with GAZYVA
• In patients who develop reactivation of HBV while receiving
GAZYVA, immediately discontinue GAZYVA and any concomitant
chemotherapy and institute appropriate treatment. Resumption
of GAZYVA in patients whose HBV reactivation resolves should be
discussed with physicians with expertise in managing hepatitis B.
Insufficient data exist regarding the safety of resuming GAZYVA in
patients who develop HBV reactivation
Progressive Multifocal Leukoencephalopathy (PML)
• JC virus infection resulting in PML, which can be fatal, was
observed in patients treated with GAZYVA. Consider the diagnosis
of PML in any patient presenting with new onset or changes to
preexisting neurologic manifestations. Evaluation of PML includes,
but is not limited to, consultation with a neurologist, brain MRI,
and lumbar puncture. Discontinue GAZYVA therapy and consider
discontinuation or reduction of any concomitant chemotherapy or
immunosuppressive therapy in patients who develop PML
Infusion Reactions
• GAZYVA can cause severe and life-threatening infusion reactions.
Thirty-eight percent of patients experienced a reaction on Day 1
during treatment with GAZYVA in combination with bendamustine.
Infusion reactions can also occur with subsequent infusions.
Symptoms may include hypotension, tachycardia, dyspnea, and
respiratory symptoms (eg, bronchospasm, larynx and throat
irritation, wheezing, and laryngeal edema). Most frequently
reported symptoms include nausea, fatigue, dizziness, vomiting,
diarrhea, hypertension, flushing, headache, pyrexia, and chills
• Premedicate patients with acetaminophen, an antihistamine,
and a glucocorticoid. Institute medical management for infusion
reactions as needed. Closely monitor patients during the entire
infusion. Infusion reactions within 24 hours of receiving GAZYVA
have occurred
• For patients with any Grade 4 infusion reactions, including but
not limited to anaphylaxis, acute life-threatening respiratory
symptoms, or other life-threatening infusion reaction: Stop the
GAZYVA infusion. Permanently discontinue GAZYVA therapy
• For patients with Grade 1, 2, o "2��gW6���&V7F���3���FW''W@�t��df�"w&FR2&V7F���2V�F��&W6��WF����b7��F��2ख�FW''WB�"&VGV6RF�R&FR�bF�R��gW6���f�"w&FR�" �&V7F���2�B��vR7��F��0��(
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