RUXIENCE®
(rituximab-pvvr) resources

An FDA-approved biosimilar* to Rituxan® (rituximab)4

The latest product monograph supporting the biosimilarity of RUXIENCE. Includes information on indications, dosing, study data (both analytical and clinical), safety, and extrapolation, as well as reimbursement and access.

RUXIENCE Product Monograph

A helpful resource for your practice, covering how to order RUXIENCE as well as potential cost savings.

RUXIENCE Product Information Brochure

Quick reference highlighting relevant billing and coding information for RUXIENCE, including HCPCS, NDC, CPT, and ICD-10-CM codes.

RUXIENCE Billing and Coding Guide
EHR Brochures

A comprehensive overview of how to leverage electronic health record (EHR) functionality, such as implementation processes, benefits verification, medication ordering, and patient communications.

Cerner
Epic
MEDITECH

*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 and the reference product.1-6

BOXED WARNINGS
FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Infusion-Related Reactions: Rituximab product administration can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related 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. Discontinue RUXIENCE in patients who experience a severe mucocutaneous reaction. The safety of readministration of RUXIENCE to patients with severe mucocutaneous reactions has not been determined
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), including fatal PML, can occur in patients receiving rituximab products. Discontinue RUXIENCE and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML
Infusion-Related Reactions (IRR)
  • Rituximab products can cause severe, including fatal, infusion-related reactions. Severe reactions typically occurred during the first infusion with time to onset of 30–120 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. For patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA), methylprednisolone 100 mg intravenously or its equivalent is recommended 30 minutes prior to each infusion. 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 preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm3)
Severe Mucocutaneous Reactions
  • Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximab products. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis
  • The onset of these reactions has been variable and includes reports with onset on the first day of rituximab exposure. Discontinue RUXIENCE in patients who experience a severe mucocutaneous reaction. The safety of readministration of rituximab products to patients with severe mucocutaneous reactions has not been determined
Hepatitis B Virus (HBV) Reactivation
  • HBV reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including rituximab products. Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also 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 (i.e., 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, i.e., increase in transaminase levels. In severe cases, increase in bilirubin levels, liver failure, and death can occur
  • Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RUXIENCE. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during RUXIENCE treatment
  • 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 RUXIENCE therapy. HBV reactivation has been reported up to 24 months following completion of rituximab therapy
  • In patients who develop reactivation of HBV while on RUXIENCE, immediately discontinue RUXIENCE and any concomitant chemotherapy, and institute appropriate treatment. Insufficient data exist regarding the safety of resuming rituximab product treatment in patients who develop HBV reactivation. Resumption of RUXIENCE treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV
Progressive Multifocal Leukoencephalopathy (PML)
  • JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in rituximab product−treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of rituximab
  • Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue RUXIENCE and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML
Tumor Lysis Syndrome (TLS)
  • Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12–24 hours after the first infusion of RUXIENCE in patients with non-Hodgkin’s lymphoma (NHL). A high number of circulating malignant cells (≥25,000/mm3), or high tumor burden, confers a greater risk of TLS
  • Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated
Infections
  • Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product−based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure)
  • New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue RUXIENCE for serious infections and institute appropriate anti-infective therapy
  • RUXIENCE is not recommended for use in patients with severe, active infections
Cardiovascular Adverse Reactions
  • Cardiac adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock, may occur in patients receiving rituximab products. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RUXIENCE for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina
Renal Toxicity
  • Severe, including fatal, renal toxicity can occur after rituximab product administration in patients with NHL. Renal toxicity has occurred in patients who experience TLS and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and RUXIENCE is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue RUXIENCE in patients with a rising serum creatinine or oliguria
Bowel Obstruction and Perforation
  • Abdominal pain, bowel obstruction, and perforation, in some cases leading to death, can occur in patients receiving rituximab products in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1–77) days in patients with NHL. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur
Immunization
  • The safety of immunization with live viral vaccines following rituximab product therapy has not been studied, and vaccination with live virus vaccines is not recommended before or during treatment
  • For patients treated with RUXIENCE, physicians should review the patient’s vaccination status and patients should, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating RUXIENCE; administer nonlive vaccines at least 4 weeks prior to a course of RUXIENCE
Embryo-Fetal Toxicity
  • Based on human data, rituximab products can cause fetal harm due to B-cell lymphocytopenia in infants exposed in utero. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RUXIENCE and for at least 12 months after the last dose
Concomitant Use with Other Biologic Agents and Disease Modifying Antirheumatic Drugs (DMARDs) in GPA and MPA
  • Limited data are available on the safety of the use of biologic agents or DMARDs. Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly. Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA or MPA patients exhibiting peripheral B-cell depletion following treatment with rituximab products
Adverse Reactions
  • The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and chronic lymphocytic leukemia (CLL) were infusion-related reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials
  • The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion-related reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials
Nursing Mothers
  • There are no data on the presence of rituximab products in human milk, the effect on the breastfed child, or the effect on milk production. However, rituximab is detected in the milk of lactating cynomolgus monkeys and IgG is present in human milk. Because of the potential of serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with RUXIENCE and for at least 6 months after the last dose
Clinical Trials Experience in GPA and MPA
  • Adverse reactions reported in ≥15% of rituximab-treated patients were infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema (other important adverse reactions include infusion-related reactions)
Induction Treatment of Patients with Active GPA/MPA (GPA/MPA Study 1)
Infusion-Related Reactions
  • In GPA/MPA Study 1, 12% vs 11% (rituximab-treated vs cyclophosphamide-treated, respectively) of patients experienced at least one infusion-related reaction. Infusion-related reactions included cytokine release syndrome, flushing, throat irritation, and tremor. In the rituximab group, the proportion of patients experiencing an infusion reaction was 12%, 5%, 4%, and 1% following the first, second, third, and fourth infusions, respectively. Patients were premedicated with antihistamine and acetaminophen before each rituximab infusion and were on background oral corticosteroids, which may have mitigated or masked an infusion-related reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion-related reactions
Infections
  • In GPA/MPA Study 1, 62% vs 47% (rituximab-treated vs cyclophosphamide-treated, respectively) of patients experienced an infection by Month 6. The most common infections in the rituximab group were upper respiratory tract infections, urinary tract infections, and herpes zoster. The incidence of serious infections was 11% vs 10% (rituximab-treated vs cyclophosphamide-treated, respectively), with rates of approximately 25 and 28 per 100 patient-years, respectively. The most common serious infection was pneumonia
Hypogammaglobulinemia
  • Hypogammaglobulinemia (IgA, IgG, or IgM below the lower limit of normal) has been observed in patients with GPA and MPA treated with rituximab in GPA/MPA Study 1. At 6 months, in the rituximab group, 27%, 58%, and 51% of patients with normal immunoglobulin levels at baseline had low IgA, IgG, and IgM levels, respectively, compared to 25%, 50%, and 46% in the cyclophosphamide group
Immunogenicity
  • A total of 23/99 (23%) rituximab-treated adult patients with GPA or MPA tested positive for anti-rituximab antibodies by 18 months in GPA/MPA Study 1. The clinical relevance of anti-rituximab antibody formation in rituximab-treated adult patients is unclear
Treatment of Patients with GPA/MPA Who Have Achieved Disease Control with Induction Treatment (GPA/MPA Study 2)
  • In GPA/MPA Study 2, the safety profile was consistent with the known safety profile of rituximab in immunologic indications
Infusion-Related Reactions (IRR)
  • In GPA/MPA Study 2, 7/57 (12%) patients in the non-US-licensed approved rituximab arm reported infusion-related reactions. The incidence of IRR symptoms was highest during or after the first infusion (9%) and decreased with subsequent infusions (<4%). One patient had two serious IRRs; two IRRs led to a dose modification; and no IRRs were severe, fatal, or led to withdrawal from the study
Infections
  • In GPA/MPA Study 2, 30/57 (53%) patients in the non-US-licensed approved rituximab arm and 33/58 (57%) in the azathioprine arm reported infections. The incidence of all-grade infections was similar between the arms. The incidence of serious infections was similar in both arms (12%). The most commonly reported serious infection in the group was mild or moderate bronchitis
INDICATIONS
  • 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)
    • In combination with fludarabine and cyclophosphamide (FC), for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL
  • Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids
Attention Healthcare Provider: Provide Medication Guide to patients prior to RUXIENCE infusion and advise patients to read guide.

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.

References:

1. NIVESTYM [prescribing information]. New York, NY: Pfizer Inc.; April 2021. 2. NYVEPRIA [prescribing information]. New York, NY: Pfizer Inc.; April 2021. 3. RETACRIT [prescribing information]. New York, NY: Pfizer Inc.; August 2020. 4. RUXIENCE [prescribing information]. New York, NY: Pfizer Inc.; May 2020. 5. TRAZIMERA [prescribing information]. New York, NY: Pfizer Inc.; November 2020. 6. ZIRABEV [prescribing information]. New York, NY: Pfizer Inc.; May 2021.

NIVESTYM, RETACRIT, RUXIENCE, TRAZIMERA, and ZIRABEV are registered trademarks of Pfizer Inc.
NYVEPRIA is a trademark of Pfizer Inc.

Avastin and Herceptin are registered trademarks of Genentech, Inc. Epogen, Neulasta, and Neupogen are registered trademarks of Amgen Inc. Procrit is a registered trademark of Janssen Products, LP. Rituxan is a registered trademark of Biogen, Inc.

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IMPORTANT SAFETY INFORMATION AND INDICATIONS
BOXED WARNINGS
FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Infusion-Related Reactions: Rituximab product administration can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related 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. Discontinue RUXIENCE in patients who experience a severe mucocutaneous reaction. The safety of readministration of RUXIENCE to patients with severe mucocutaneous reactions has not been determined
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), including fatal PML, can occur in patients receiving rituximab products. Discontinue RUXIENCE and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML
Infusion-Related Reactions (IRR)
Severe Mucocutaneous Reactions
Hepatitis B Virus (HBV) Reactivation
Progressive Multifocal Leukoencephalopathy (PML)
Tumor Lysis Syndrome (TLS)
Infections
Cardiovascular Adverse Reactions
Renal Toxicity
Bowel Obstruction and Perforation
Immunization
Embryo-Fetal Toxicity
Concomitant Use with Other Biologic Agents and Disease Modifying Antirheumatic Drugs (DMARDs) in GPA and MPA
Adverse Reactions
Nursing Mothers
Clinical Trials Experience in GPA and MPA
Induction Treatment of Patients with Active GPA/MPA (GPA/MPA Study 1)
Infusion-Related Reactions
Infections
Hypogammaglobulinemia
Immunogenicity
Treatment of Patients with GPA/MPA Who Have Achieved Disease Control with Induction Treatment (GPA/MPA Study 2)
Infusion-Related Reactions (IRR)
Infections
INDICATIONS
Attention Healthcare Provider: Provide Medication Guide to patients prior to RUXIENCE infusion and advise patients to read guide.

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.