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 .