Brief Summary of Prescribing Information for RUXIENCE™ ( rituximab-pvvr ) injection , for intravenous use Initial U . S . Approval : 2019 RUXIENCE ( rituximab-pvvr ) is biosimilar * to RITUXAN ( rituximab ). * Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product , known as a reference product , and that there are no clinically meaningful differences between the biosimilar product and the reference product . Biosimilarity of RUXIENCE has been demonstrated for the condition ( s ) of use ( e . g . indication ( s ), dosing regimen ( s ), strength ( s ), dosage form ( s ), and route ( s ) of administration described in its Full Prescribing Information . WARNING : FATAL INFUSION-RELATED REACTIONS , SEVERE MUCOCUTANEOUS REACTIONS , HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY Infusion-Related Reactions
Administration of rituximab products can result in serious , including fatal , infusion-related reactions . Deaths within 24 hours of rituximab infusion have occurred . Approximately 80 % of fatal infusion reactions occurred in association with the first infusion . Monitor patients closely . Discontinue RUXIENCE infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions .
Severe Mucocutaneous Reactions
Severe , including fatal , mucocutaneous reactions can occur in patients receiving rituximab products .
Hepatitis B Virus ( HBV ) Reactivation
HBV reactivation can occur in patients treated with rituximab products , in some cases resulting in fulminant hepatitis , hepatic failure , and death . Screen all patients for HBV infection before treatment initiation , and monitor patients during and after treatment with RUXIENCE . Discontinue RUXIENCE and concomitant medications in the event of HBV reactivation .
Progressive Multifocal Leukoencephalopathy ( PML )
Progressive Multifocal Leukoencephalopathy ( PML ), including fatal PML , can occur in patients receiving rituximab products .
INDICATIONS AND USAGE Non-Hodgkin ’ s Lymphoma ( NHL ) RUXIENCE ( rituximab-pvvr ) is indicated for the treatment of adult patients with :
• Relapsed or refractory , low-grade or follicular , CD20-positive , B-cell NHL as a single agent .
• Previously untreated follicular , CD20-positive , B-cell NHL in combination with first line chemotherapy and , in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy , as single-agent maintenance therapy .
• Non-progressing ( including stable disease ), low-grade , CD20-positive , B-cell NHL as a single agent after first-line cyclophosphamide , vincristine , and prednisone ( CVP ) chemotherapy .
• Previously untreated diffuse large B-cell , CD20-positive NHL in combination with cyclophosphamide , doxorubicin , vincristine , prednisone ( CHOP ) or other anthracycline-based chemotherapy regimens .
Chronic Lymphocytic Leukemia ( CLL ) RUXIENCE , in combination with fludarabine and cyclophosphamide ( FC ), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL .
DOSAGE AND ADMINISTRATION
Important Dosing Information Administer only as an intravenous infusion . Do not administer as an intravenous push or bolus . RUXIENCE should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur .
Premedicate before each infusion .
Prior to First Infusion : Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RUXIENCE . Obtain complete blood counts ( CBC ) including platelets prior to the first dose .
During RUXIENCE Therapy : In patients with lymphoid malignancies , during treatment with RUXIENCE monotherapy , obtain complete blood counts ( CBC ) with differential and platelet counts prior to each RUXIENCE course . During treatment with RUXIENCE and chemotherapy , obtain CBC with differential and platelet counts at weekly to monthly intervals and more frequently in patients who develop cytopenias . Continue to monitor for cytopenias after final dose and until resolution .
• First Infusion : Initiate infusion at a rate of 50 mg / hour . In the absence of infusion toxicity , increase infusion rate by 50 mg / hour increments every 30 minutes , to a maximum of 400 mg / hour .
• Subsequent Infusions : Standard Infusion : Initiate infusion at a rate of 100 mg / hour . In the absence of infusion toxicity , increase rate by 100 mg / hour increments at 30-minute intervals , to a maximum of 400 mg / hour .
For Previously Untreated Follicular NHL and DLBCL Patients : If patients did not experience a Grade 3 or 4 infusion-related adverse event during Cycle 1 , a 90-minute infusion can be administered in Cycle 2 with a glucocorticoid-containing chemotherapy regimen .
Initiate at a rate of 20 % of the total dose given in the first 30 minutes and the remaining 80 % of the total dose given over the next 60 minutes . If the 90-minute infusion is tolerated in Cycle 2 , the same rate can be used when administering the remainder of the treatment regimen ( through Cycle 6 or 8 ).
Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count ≥5,000 / mm 3 before Cycle 2 should not be administered the 90-minute infusion .
• Interrupt the infusion or slow the infusion rate for infusion-related reactions . Continue the infusion at one-half the previous rate upon improvement of symptoms .
Recommended Dose for Non-Hodgkin ’ s Lymphoma ( NHL ) The recommended dose is 375 mg / m 2 as an intravenous infusion according to the following schedules :
• Relapsed or Refractory , Low-Grade or Follicular , CD20-Positive , B-Cell NHL Administer once weekly for 4 or 8 doses .
• Retreatment for Relapsed or Refractory , Low-Grade or Follicular , CD20- Positive , B-Cell NHL Administer once weekly for 4 doses .
• Previously Untreated , Follicular , CD20-Positive , B-Cell NHL Administer on Day 1 of each cycle of chemotherapy for up to 8 doses . In patients with complete or partial response , initiate RUXIENCE maintenance eight weeks following completion of a rituximab product in combination with chemotherapy . Administer RUXIENCE as a single-agent every 8 weeks for 12 doses .
• Non-progressing , Low-Grade , CD20-Positive , B-Cell NHL , after first-line CVP chemotherapy Following completion of 6-8 cycles of CVP chemotherapy , administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses .
• Diffuse Large B-Cell NHL Administer on Day 1 of each cycle of chemotherapy for up to 8 infusions .
Recommended Dose for Chronic Lymphocytic Leukemia ( CLL ) The recommended dose is 375 mg / m 2 the day prior to the initiation of FC chemotherapy , then 500 mg / m 2 on Day 1 of Cycles 2-6 ( every 28 days ).
Recommended Dose as a Component of Zevalin ® for Treatment of NHL When used as part of the Zevalin therapeutic regimen , infuse 250 mg / m 2 in accordance with the Zevalin package insert . Refer to the Zevalin package insert for full prescribing information regarding the Zevalin therapeutic regimen .
Recommended Dose for Premedication and Prophylactic Medications Premedicate with acetaminophen and an antihistamine before each infusion of RUXIENCE . For patients administered RUXIENCE according to the 90-minute infusion rate , the glucocorticoid component of their chemotherapy regimen should be administered prior to infusion .
Administration and Storage Use appropriate aseptic technique . Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration . RUXIENCE should be a clear to slightly opalescent , colorless to pale brownish-yellow liquid . Do not use vial if particulates or discoloration is present .
Administration Withdraw the necessary amount of RUXIENCE and dilute to a final concentration of 1 mg / mL to 4 mg / mL in an infusion bag containing either 0.9 % Sodium Chloride , USP , or 5 % Dextrose Injection , USP . Gently invert the bag to mix the solution . Do not mix or dilute with other drugs . Discard any unused portion left in the vial .
Storage
Diluted RUXIENCE solutions for infusion may be stored at 2 ° C to 8 ° C ( 36 ° F to 46 ° F ) for 24 hours . Complete administration within 8 hours from removal from refrigeration . No incompatibilities between RUXIENCE and polyvinylchloride bags have been observed .
CONTRAINDICATIONS None .
WARNINGS AND PRECAUTIONS Infusion-Related Reactions Rituximab products can cause severe , including fatal , infusion-related reactions . Severe reactions typically occurred during the first infusion with time to onset of 30 to 120 minutes . Rituximab product-induced infusion-related reactions and sequelae include urticaria , hypotension , angioedema , hypoxia , bronchospasm , pulmonary infiltrates , acute respiratory distress syndrome , myocardial infarction , ventricular fibrillation , cardiogenic shock , anaphylactoid events , or death .
Premedicate patients with an antihistamine and acetaminophen prior to dosing . Institute medical management ( e . g . glucocorticoids , epinephrine , bronchodilators , or oxygen ) for infusion-related reactions as needed . Depending on the severity of the infusion-related reaction and the required interventions , temporarily or permanently discontinue RUXIENCE . Resume infusion at a minimum 50 % reduction in rate after symptoms have resolved . Closely monitor the following patients : those with pre-