For Patients and Caregivers

Financial Assistance Options

No matter what type of health insurance your patient has, they may have options to help them afford their medicine. Options may be available to your patient even if they have no insurance at all.

Get Started with Financial Assistance Tool

Use our financial assistance tool to see which programs may be right for your patient.

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If you would rather talk through some potential options, call us at 866-4ACCESS (866-422-2377) (6AM-5PM PST, Monday through Friday).

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RITUXAN Immunology Co-pay Program
Independent Co-pay Assistance Foundations
Genentech Patient Foundation

Help With Co-pay Costs

These programs help your patient pay for RITUXAN if they have insurance but still need help with costs:

Help With Costs for RITUXAN

Co-pay Card Assistance

With the RITUXAN Immunology Co-pay Program, eligible patients with commercial insurance could pay as little as $5 per 30-day supply of RITUXAN. The rest of your co-pay or co-insurance is covered, up to $15,000 in assistance per calendar year.

Your patient may be eligible if they:

  • Are taking RITUXAN for an FDA-approved use
  • Are 18 years of age or older or have a Legally Authorized Person over the age of 18 to manage the program
  • Have commercial (private or non-governmental) insurance. This includes plans available through state and federal health insurance exchanges
  • Live and receive treatment in the United States or U.S. Territories
  • Are not receiving assistance through the Genentech Patient Foundation or any other charitable organization for the same expenses covered by the program
  • Do not use a state or federal healthcare plan to pay for your medication. This includes, but is not limited to, Medicare, Medicaid and TRICARE

Help With Costs for Administration

Co-pay Card Assistance

With the RITUXAN Immunology Co-pay Program, eligible patients with commercial insurance could pay as little as $5 per RITUXAN Immunology administration co-pay. Co-pay assistance is provided up to $2,000 per calendar year.

Your patient may be eligible if they:

  • Are taking RITUXAN for an FDA-approved use
  • Are 18 years of age or older or have a Legally Authorized Person over the age of 18 to manage the program
  • Have commercial (private or non-governmental) insurance. This includes plans available through state and federal health insurance exchanges
  • Live and receive treatment in the United States or U.S. Territories
  • Are not receiving assistance from any charitable organization for the same expenses covered by the program*
  • Do not use a state or federal healthcare plan to pay for your therapy. This includes, but is not limited to, Medicare, Medicaid and TRICARE
  • Do not live or get treatments in certain states (Massachusetts or Rhode Island)

*Patients may use the RITUXAN Immunology Co-pay Program for their administration costs if they are receiving their medicine from the Genentech Patient Foundation.

The Product and Administration Co-pay Programs (“Programs”) are valid ONLY for patients with commercial (private or non-governmental) insurance who have a valid prescription for a Food and Drug Administration (FDA)-approved indication of a Genentech medicine. Patients using Medicare, Medicaid or any other federal or state government program (collectively, “Government Programs”) to pay for their Genentech medicine and/or administration services are not eligible.

Under the Programs, the patient may be required to pay a co-pay for drug costs and a co-pay for administration costs. The final amount owed by a patient may be as little as $0 for the Genentech medicine or administration of the Genentech medicine (see Program specific details available at the Program website). The total patient out-of-pocket cost is dependent on the patient’s health insurance plan. The Programs assist with the cost of the Genentech medicine and the Genentech medicine administration only. It does not assist with the cost of other administrations, medicines, procedures or office visit fees. After reaching the maximum Programs’ benefit amounts, the patient will be responsible for all remaining out-of-pocket expenses. The amount of the Programs’ benefits cannot exceed the patient’s out-of-pocket expenses for the cost of the Genentech medicine or administration fees for the Genentech medicine.

All participants are responsible for reporting the receipt of all Programs’ benefits as required by any insurer or by law. The Programs are only valid in the United States and U.S. Territories and are void where prohibited by law. The Drug Co-pay Program shall follow state restrictions in relation to AB-rated generic equivalents (e.g., MA, CA) where applicable. The Administration Co-pay Program is not valid for Massachusetts or Rhode Island residents. No party may seek reimbursement for all or any part of the benefit received through the Programs. The value of the Programs is intended exclusively for the benefit of the patient. The funds made available through the Programs may only be used to reduce the out-of-pocket costs for the patient enrolled in the Programs. The Programs are not intended for the benefit of third parties, including without limitation third party payers, pharmacy benefit managers, or their agents. If Genentech determines that a third party has implemented programs that adjust patient cost-sharing obligations based on the availability of support under the Programs and/or excludes the assistance provided under the Programs from counting towards the patient’s deductible or out-of-pocket cost limitations, Genentech may impose a per fill cap on the cost-sharing assistance available under the Programs. Submission of true and accurate information is a requirement for eligibility and Genentech reserves the right to disqualify patients who do not comply from Genentech programs. Genentech reserves the right to rescind, revoke or amend the Programs without notice at any time.

Additional terms and conditions apply. Please visit the co-pay Program website for the full list of Terms and Conditions.

View full TERMS AND CONDITIONS

Patients may qualify for drug assistance, administration assistance or both, depending on whether they meet the eligibility criteria.

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Independent Co-pay Assistance Foundations - Organizations for Nephrology

Independent Co-pay Assistance

An independent co-pay assistance foundation is a charitable organization providing financial assistance to patients with specific disease states, regardless of treatment. Patients who are commercially or publicly insured, including those covered by Medicare and Medicaid, can contact the foundations directly to request assistance. Eligibility requirements, all aspects of the application process, turnaround times and the type or amount of assistance available (if any) can vary by foundation. 

These foundations may be able to help. Please check their websites for up-to-date information.

Advise your patient that these organizations are independent of Genentech and may require the patient to provide personal or financial information directly to the organization to enroll in their respective programs. Genentech cannot share any information the patient has provided to us.

Independent co-pay assistance foundations have their own rules for eligibility. We have no involvement or influence in independent foundation decision-making or eligibility criteria and do not know if a foundation will be able to help your patient. We can only refer your patient to a foundation that supports their disease state. This information is provided as a resource for you. We do not endorse or show preference for any particular foundation. The foundations in this list may not be the only ones that might be able to help your patient.

Genentech Patient Foundation

If patients don’t have health insurance coverage for RITUXAN or have financial concerns and meet eligibility criteria, this program may help:

Genentech Patient Foundation

The Genentech Patient Foundation gives free RITUXAN to people who have been prescribed this medicine and don’t have insurance or that have financial concerns and meet certain eligibility criteria.

Your patient may be eligible if their insurance coverage and income match one of these situations:

  • Uninsured patients with incomes under $150,000
  • Insured patients without coverage for RITUXAN with incomes under $150,000
  • Insured patients with coverage for a Genentech medicine:
    • With an out-of-pocket maximum set by their health insurance plan that exceeds 7.5% of their household income
    • With household size and income within certain guidelines

For any of these situations, add $25,000 for each extra person in households larger than 4 people.

We encourage insured patients to try other financial assistance options before applying for help from the Genentech Patient Foundation, if possible.

Enrollment Process for the Genentech Patient Foundation

Get started with enrollment by following the steps below.

Option 1: Submit online

If your practice has a registered account for My Patient Solutions, you can get started by logging into your account.

Don't have an account?

Your patient is required to complete the Patient Consent Form. You can either upload their Patient Consent Form as part of your application or have your patient submit the form via fax, text or e-submit.

  • An online tool to help you enroll patients in RITUXAN Immunology Access Solutions and manage your service requests at your convenience.

Option 2: Print & fax or text

Step 1: Print one of the Patient Consent Forms below for your patient to complete.

Step 2: Print and complete the Prescriber Foundation Form below.

Step 3: Submit the completed forms via fax or text.

Both forms are required. We must have both the Patient Consent Form and the Prescriber Foundation Form before we can help you. 

What to expect next:

  • The request will be processed within five business days upon receipt of both required forms.
  • Your office will be contacted to discuss any next steps.

If you have any questions about the criteria, please contact a Foundation Specialist at 888-941-3331 (Mon.–Fri., 6AM–5PM PST).

Get Started with Financial Assistance Tool

Use our financial assistance tool to see which programs may be right for your patient.

Get started

  • Commercial insurance: An insurance plan you get from a private health insurance company. This can be insurance from your job, from a plan you bought yourself or from a Health Insurance Marketplace. Medicare and Medicaid are not considered commercial insurance. 

  • Public insurance: A health insurance plan you get from the federal or state government. This includes Medicare, Medicaid, TRICARE and DoD/VA insurance.

  • For example, a household size of 1 with income of less than $75,000 may meet the criteria for assistance. Add $25,000 for each additional person in the household. There is no maximum number of people you may add.

IMPORTANT SAFETY INFORMATION

INDICATIONS

  • Rituxan® (rituximab), in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more TNF antagonist therapies
  • Rituxan® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)
  • Rituxan® (rituximab) is indicated for the treatment of adult patients with moderate to severe pemphigus vulgaris (PV)

BOXED WARNINGS and Additional Important Safety Information

BOXED WARNINGS

Infusion-Related Reactions: Rituxan administration can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Monitor patients closely. Discontinue Rituxan infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions. 

Severe reactions typically occurred during the first infusion with time to onset of 30 to 120 minutes. Rituxan-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 RA, GPA and MPA, and PV patients, methylprednisolone 100 mg intravenously or its equivalent is recommended 30 minutes prior to each infusion. For GPA and MPA patients, glucocorticoids are given in combination with Rituxan. Institute medical management (eg, 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 Rituxan. Resume infusion at a minimum of 50% reduction in the rate after symptoms have resolved. Closely monitor the following patients: those with pre-existing 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: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan. 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 Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with Rituxan, 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 Rituxan. Discontinue Rituxan and concomitant medications in the event of HBV reactivation. 

Hepatitis B virus (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 Rituxan. 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 also has 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. 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 Rituxan. 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 Rituxan 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 Rituxan therapy. HBV reactivation has been reported up to 24 months following completion of Rituxan therapy. 

In patients who develop reactivation of HBV while on Rituxan, immediately discontinue Rituxan and any concomitant chemotherapy and institute appropriate treatment. Insufficient data exist regarding the safety of resuming Rituxan treatment in patients who develop HBV reactivation. Resumption of Rituxan 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 PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML have received Rituxan 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 Rituxan. 

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 Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Warnings and Precautions

Tumor Lysis Syndrome (TLS): Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of Rituxan in patients with Non–Hodgkin’s Lymphoma (NHL). 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 Rituxan-based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after Rituxan 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 Rituxan for serious infections and institute appropriate anti-infective therapy. Rituxan 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 Rituxan. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan 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 Rituxan administration in patients with Non–Hodgkin’s Lymphoma (NHL). Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue Rituxan 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 Rituxan in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization: The safety of immunization with live viral vaccines following Rituxan therapy has not been studied, and vaccination with live virus vaccines is not recommended before or during treatment.

For patients treated with Rituxan, 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 Rituxan and administer non-live vaccines at least 4 weeks prior to a course of Rituxan. 

The effect of Rituxan on immune responses was assessed in a randomized, controlled study in patients with RA treated with Rituxan and methotrexate (MTX) compared to patients treated with MTX alone. 

A response to pneumococcal vaccination (a T-cell independent antigen) as measured by an increase in antibody titers to at least 6 of 12 serotypes was lower in patients treated with Rituxan plus MTX as compared to patients treated with MTX alone (19% vs 61%). A lower proportion of patients in the Rituxan plus MTX group developed detectable levels of anti-keyhole limpet hemocyanin antibodies (a novel protein antigen) after vaccination compared to patients on MTX alone (47% vs 93%). 

A positive response to tetanus toxoid vaccine (a T-cell dependent antigen with existing immunity) was similar in patients treated with Rituxan plus MTX compared to patients on MTX alone (39% vs 42%). The proportion of patients maintaining a positive Candida skin test (to evaluate delayed type hypersensitivity) was also similar (77% of patients on Rituxan plus MTX vs 70% of patients on MTX alone).

Most patients in the Rituxan-treated group had B-cell counts below the lower limit of normal at the time of immunization. The clinical implications of these findings are not known.

Embryo-Fetal Toxicity: Based on human data, Rituxan can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in-utero. Advise pregnant women of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to initiating Rituxan. Advise females of reproductive potential to use effective contraception while receiving Rituxan and for 12 months after the last dose.

Concomitant Use with Biologic Agents and DMARDs Other Than MTX: Limited data are available on the safety of the use of biologic agents or DMARDs other than MTX in RA patients exhibiting peripheral B-cell depletion following treatment with Rituxan. 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, MPA, or PV patients exhibiting peripheral B-cell depletion following treatment with Rituxan.

Use in Patients With RA Who Had No Prior Inadequate Response to Tumor Necrosis Factor (TNF) Antagonists: While the efficacy of Rituxan was supported in 4 controlled trials in patients with RA with prior inadequate responses to nonbiologic DMARDs and in a controlled trial in MTX-naïve patients, a favorable risk-benefit relationship has not been established in these populations. The use of Rituxan in patients with RA who have not had prior inadequate response to one or more TNF antagonists is not recommended.

Adverse Reactions

Clinical Trials Experience in RA

Among all exposed patients, adverse reactions reported in greater than 10% of patients include infusion-related reactions, upper respiratory tract infection, nasopharyngitis, urinary tract infection, and bronchitis.

In placebo-controlled studies, adverse reactions reported in ≥5% of patients were hypertension (8% vs 5%), nausea (8% vs 5%), upper respiratory tract infection (7% vs 6%), arthralgia (6% vs 4%), pyrexia (5% vs 2%), and pruritus (5% vs 1%) of Rituxan-treated vs placebo, respectively.

Infusion-Related Reactions: In the Rituxan RA pooled, placebo-controlled studies, incidence of any adverse event within 24 hours of an infusion was 32% vs 23% after the first infusion, and 11% vs 13% after the second infusion in the Rituxan-treated patients and placebo group, respectively. Incidence of acute infusion-related reactions was 27% vs 19% after the first infusion, 9% vs 11% after the second infusion in the Rituxan-treated patients and placebo group, respectively. Serious acute infusion-related reactions were experienced by <1% of patients in either treatment group. Acute infusion-related reactions required dose modification (stopping, slowing, or interruption of the infusion) in 10% and 2% of patients receiving Rituxan or placebo, respectively, after the first course.

Infections: In the pooled, placebo controlled studies, incidence of any type of infection was 39% vs 34%, Rituxan-treated vs placebo. The most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis. The incidence of serious infections was 2% vs 1%, Rituxan-treated vs placebo group.

In the experience with Rituxan in 2578 RA patients, the rate of serious infection was 4.31 per 100 patient-years. The most common serious infections (≥0.5%) were pneumonia or lower respiratory tract infections, cellulitis, and urinary tract infections. Fatal serious infections included pneumonia, sepsis, and colitis. Rates of serious infection remain stable in patients receiving subsequent courses.

In 185 Rituxan-treated RA patients with active disease, subsequent treatment with a biologic DMARD, the majority of which were TNF antagonists, did not appear to increase the rate of serious infection.

Cardiovascular Adverse Reactions: In the pooled, placebo-controlled studies, incidence of serious cardiovascular reactions was 1.7% vs 1.3% Rituxan-treated vs placebo. Three cardiovascular deaths occurred during the double-blind period of the RA studies including all Rituxan regimens (3/769=0.4%) compared to none in the placebo treatment group (0/389). In the experience with Rituxan in 2578 RA patients, the rate of myocardial infarction (MI) was consistent with MI rates in the general RA population. Rituxan should be discontinued in the event of a serious or life-threatening cardiac event.

Hypophosphatemia and Hyperuricemia: In the pooled, placebo-controlled studies, newly occurring hypophosphatemia (<2.0 mg/dL) was 12% vs 10%, Rituxan-treated vs placebo, respectively. Hypophosphatemia was more common in patients who received corticosteroids. Newly occurring hyperuricemia (>10 mg/dL) was observed in 1.5% vs 0.3%, Rituxan-treated vs placebo, respectively.

Retreatment in Patients With RA: In the experience with Rituxan in RA patients, 2578 patients have been exposed to Rituxan and have received up to 10 courses of Rituxan in RA clinical trials, with 1890, 1043, and 425 patients having received at least 2, 3, and 4 courses, respectively. Most of the patients who received additional courses did so 24 weeks or more after the previous course and none were retreated sooner than 16 weeks. The rates and types of adverse reactions reported for subsequent courses of Rituxan were similar to rates and types seen for a single course of Rituxan. In RA Study 2, where all patients initially received Rituxan, the safety profile of patients who were retreated with Rituxan was similar to those who were retreated with placebo.

Immunogenicity

A total of 273/2578 (11%) patients with RA tested positive for anti-rituximab antibodies at any time after receiving Rituxan. Anti-rituximab antibody positivity was not associated with increased infusion-related reactions or other adverse reactions. Upon further treatment, the proportions of patients with infusion-related reactions were similar between anti-rituximab antibody positive and negative patients, and most reactions were mild to moderate. Four anti-rituximab antibody positive patients had serious infusion-related reactions, and the temporal relationship between anti-rituximab antibody positivity and infusion-related reaction was variable. The clinical relevance of anti-rituximab antibody formation in Rituxan-treated patients is unclear.

Clinical Trials Experience in GPA and MPA

Adverse reactions reported in ≥15% of Rituxan-treated patients were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, 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% (Rituxan-treated vs cyclophosphamide) of patients experienced at least one infusion-related reaction. Infusion-related reactions included cytokine release syndrome, flushing, throat irritation, and tremor. In the Rituxan group, the proportion of patients experiencing an infusion-related 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 Rituxan 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% (Rituxan-treated vs cyclophosphamide-treated, respectively) of patients experienced an infection by Month 6. The most common infections in the Rituxan group were upper respiratory tract infections, urinary tract infections, and herpes zoster. The incidence of serious infections was 11% vs 10% (Rituxan-treated vs cyclophosphamide, 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 Rituxan in GPA/MPA Study 1. At 6 months, in the Rituxan 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 cyclophosphamide group.

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 Rituxan in immunologic indications.

Infusion-Related Reactions: In GPA/MPA Study 2, 7/57 (12%) patients in the EU-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 EU-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.

Treatment of Pediatric Patients with GPA/MPA (GPA/MPA Study 4)
The safety profile in pediatric GPA and MPA patients was consistent in type, nature and severity with the known safety profile of Rituxan in adult patients with FDA-approved immunological indications.

Infusion-Related Reactions
In GPA/MPA Study 4, the proportion of patients experiencing an IRR was 32%, 20%, 12%, and 8% following the first, second, third, and fourth infusions, respectively. The observed symptoms of IRRs were similar to those in adult GPA and MPA patients treated with Rituxan.

Serious Infections
In GPA/MPA Study 4, serious infections were reported in 7 patients (28%), and included influenza (2 patients [8%]) and lower respiratory tract infection (2 patients [8%]) as the most frequently reported events.

Hypogammaglobulinemia
Hypogammaglobulinemia (IgG or IgM below the lower limit of normal), including prolonged hypogammaglobulinemia (defined as Ig levels below lower limit of normal for at least 4 months) was observed in GPA/MPA Study 4. During the overall study period, 18/25 patients (72%) had prolonged low IgG levels, including 15 patients who also had prolonged low IgM. Three patients received treatment with intravenous immunoglobulin

Immunogenicity

A total of 23/99 (23%) Rituxan-treated 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 Rituxan-treated patients is unclear. In GPA/MPA Study 4, a total of 4/21 (19%) Rituxan-treated pediatric patients with GPA and MPA developed anti-rituximab antibodies during the overall study period (assessed at Month 18).

Clinical Trials Experience in Pemphigus Vulgaris (PV)

Adverse reactions reported in ≥10% of patients treated with the Ritux 3 regimen* vs patients treated with prednisone monotherapy were infusion-related reactions (58% vs N/A), depression (18% vs 11%), herpes simplex (13% vs 3%), and alopecia (13% vs 0%). 

Infusion-Related Reactions
Infusion-related reactions were the most commonly reported adverse drug reactions (58%) with the Ritux 3 regimen. Infusion-related reactions included symptoms collected on the next scheduled visit after each infusion, and adverse events occurring on the day of or one day after the infusion. The most common infusion-related reactions included headaches, chills, high blood pressure, nausea, asthenia and pain. All infusion-related reactions were mild to moderate (Grade 1 or 2) except one Grade 3 serious infusion-related reaction (arthralgia) associated with the Month 12 maintenance infusion. The proportion of patients experiencing an infusion-related reaction was 29%, 40%, 13%, and 10% following the first, second, third, and fourth infusions, respectively. No patients were withdrawn from treatment due to infusion-related reactions. 

Infections
Fourteen patients (37%) treated with the Ritux 3 regimen experienced treatment-related infections compared to 15 patients (42%) treated with prednisone monotherapy. The most common infections in patients treated with the Ritux 3 regimen were herpes simplex, herpes zoster, bronchitis, urinary tract infection, fungal infection, and conjunctivitis. Three patients (8%) treated with the Ritux 3 regimen experienced a total of 5 serious infections (Pneumocystis jirovecii pneumonia, infective thrombosis, intervertebral discitis, lung infection, Staphylococcal sepsis) and 1 patient (3%) treated with prednisone monotherapy experienced 1 serious infection (Pneumocystis jirovecii pneumonia).

Immunogenicity

Using a new ELISA assay, a total of 19/34 (56%) patients with PV treated with the Ritux 3 regimen tested positive for anti-rituximab antibodies by 18 months. The clinical relevance of anti-rituximab antibody formation in Rituxan treated PV patients is unclear.

Additional Important Safety Information

Lactation

Rituxan has been reported to be excreted at low concentrations in human breast milk. Given that the clinical significance of this finding for children is not known, advise women not to breastfeed during treatment with Rituxan and for 6 months after the last dose due to the potential for serious adverse reactions in breastfed children.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional Important Safety Information, please see the Rituxan full Prescribing Information, including BOXED WARNINGS.

*Ritux 3 regimen = Roche-manufactured, EU-approved rituximab product
EU=European Union

Attention Healthcare Provider: Provide Medication Guide to patient prior to Rituxan infusion.

See full safety and Boxed Warning for more information.

    • Rituxan [package insert]. South San Francisco, CA: Biogen and Genentech USA, Inc.

      Rituxan [package insert]. South San Francisco, CA: Biogen and Genentech USA, Inc.

    • Stone JH, Merkel PA, Spiera R, et al; for RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232.

      Stone JH, Merkel PA, Spiera R, et al; for RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232.

    • Stone JH, Hoffman GS, Merkel PA, et al; for International Network for the Study of the Systemic Vasculitides (INSSYS). A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum. 2001;44(4):912-920.

      Stone JH, Hoffman GS, Merkel PA, et al; for International Network for the Study of the Systemic Vasculitides (INSSYS). A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum. 2001;44(4):912-920.

    • Silverman GJ, Weisman S. Rituximab therapy and autoimmune disorders: prospects for anti-B cell therapy. Arthritis Rheum. 2003;48(6):1484-1492.

      Silverman GJ, Weisman S. Rituximab therapy and autoimmune disorders: prospects for anti-B cell therapy. Arthritis Rheum. 2003;48(6):1484-1492.

    • Mease PJ, Cohen S, Gaylis NB, et al. Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial. J Rheumatol. 2010;37:917-927.

      Mease PJ, Cohen S, Gaylis NB, et al. Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial. J Rheumatol. 2010;37:917-927.

    • Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771-1780.

      Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771-1780.

    • Specks U, Merkel PA, Seo P, et al; for RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369(5):417-427.

      Specks U, Merkel PA, Seo P, et al; for RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369(5):417-427.

    • Genovese MC, Breedveld FC, Emery P, et al. Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009;68(12):1894-1897.

      Genovese MC, Breedveld FC, Emery P, et al. Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients. Ann Rheum Dis. 2009;68(12):1894-1897.

    • Genovese MC, et al. Presented at American College of Rheumatology; November 6-11, 2010; Atlanta, GA. Poster 403.

      Genovese MC, et al. Presented at American College of Rheumatology; November 6-11, 2010; Atlanta, GA. Poster 403.

    • Cohen SB, Keystone E, Genovese MC, et al. Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate. Ann Rheum Dis. 2010;69(6):1158-1161.

      Cohen SB, Keystone E, Genovese MC, et al. Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate. Ann Rheum Dis. 2010;69(6):1158-1161.

    • Cohen SB, Emery P, Greenwald MW, et al; for the REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54(9):2793-2806.

      Cohen SB, Emery P, Greenwald MW, et al; for the REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54(9):2793-2806.

    • Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006;54(5):1390-1400.

      Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006;54(5):1390-1400.

    • Keystone E, Emery P, Peterfy CG, et al. Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2009;68:216-221.

      Keystone E, Emery P, Peterfy CG, et al. Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2009;68:216-221.

    • van Vollenhoven RF, Emery P, Bingham CO III, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37(3):558-567.

      van Vollenhoven RF, Emery P, Bingham CO III, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37(3):558-567.

    • Emery P, Deodhar A, Rigby WF, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010;69(9):1629-1635.

      Emery P, Deodhar A, Rigby WF, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010;69(9):1629-1635.

    • Bingham CO III, Looney RJ, Deodhar A, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab; results from a controlled clinical trial. Arthritis Rheum. 2010;62(1):64-74.

      Bingham CO III, Looney RJ, Deodhar A, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab; results from a controlled clinical trial. Arthritis Rheum. 2010;62(1):64-74.

    • Rubbert-Roth A, Tak PP, Zerbini C, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR). Rheumatology (Oxford). 2010;49(9):1683-1693.

      Rubbert-Roth A, Tak PP, Zerbini C, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR). Rheumatology (Oxford). 2010;49(9):1683-1693.

    • Tak PP, Rigby WF, Rubbert-Roth A, et al; for the IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70(1):39-46.

      Tak PP, Rigby WF, Rubbert-Roth A, et al; for the IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70(1):39-46.

    • Greenwald MW, Shergy WJ, Kaine JL, et al. Evaluation of the safety of rituximab in combination with a tumor necrosis factor inhibitor and methotrexate in patients with active rheumatoid arthritis: results from a randomized controlled trial. Arthritis Rheum. 2011;63(3):622-632.

      Greenwald MW, Shergy WJ, Kaine JL, et al. Evaluation of the safety of rituximab in combination with a tumor necrosis factor inhibitor and methotrexate in patients with active rheumatoid arthritis: results from a randomized controlled trial. Arthritis Rheum. 2011;63(3):622-632.

    • Haraoui B, Bokarewa M, Kallmeyer I, Bykerk VP; for the RESET Investigators. Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an inadequate response to 1 prior tumor necrosis factor inhibitor: the RESET Trial. J Rheumatol. 2011;38(12):2548-2556.

      Haraoui B, Bokarewa M, Kallmeyer I, Bykerk VP; for the RESET Investigators. Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an inadequate response to 1 prior tumor necrosis factor inhibitor: the RESET Trial. J Rheumatol. 2011;38(12):2548-2556.

    • Keystone EC, Cohen SB, Emery P, et al. Multiple courses of rituximab produce sustained clinical and radiographic efficacy and safety in patients with rheumatoid arthritis and an inadequate response to 1 or more tumor necrosis factor inhibitors: 5-year data from the REFLEX study. J Rheumatol. 2012;39(12):2238-2246.

      Keystone EC, Cohen SB, Emery P, et al. Multiple courses of rituximab produce sustained clinical and radiographic efficacy and safety in patients with rheumatoid arthritis and an inadequate response to 1 or more tumor necrosis factor inhibitors: 5-year data from the REFLEX study. J Rheumatol. 2012;39(12):2238-2246.

    • van Vollenhoven RF, Emery P, Bingham CO, et al. Presented at: European League Against Rheumatism Conference; June 12-15, 2013; Madrid, Spain. Poster SAT0131.

      van Vollenhoven RF, Emery P, Bingham CO, et al. Presented at: European League Against Rheumatism Conference; June 12-15, 2013; Madrid, Spain. Poster SAT0131.

    • Data on file, EULAR 2018 PePRS. Genentech USA, Inc.

      Data on file, EULAR 2018 PePRS. Genentech USA, Inc.

    • Joly C, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicenter, parallel-group, open-label randomized trial. Lancet. 2017;389(10083):2031-2040.

      Joly C, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicenter, parallel-group, open-label randomized trial. Lancet. 2017;389(10083):2031-2040.

    • van Vollenhoven RF, Emery P, Bingham CO III, et al. Long-term safety of rituximab: 6-year follow-up of the rheumatoid arthritis (RA) clinical trials and re-treatment population. Presented at: American College of Rheumatology Annual Scientific Meeting; October 24-29, 2008; San Francisco, CA. Poster 361.

      van Vollenhoven RF, Emery P, Bingham CO III, et al. Long-term safety of rituximab: 6-year follow-up of the rheumatoid arthritis (RA) clinical trials and re-treatment population. Presented at: American College of Rheumatology Annual Scientific Meeting; October 24-29, 2008; San Francisco, CA. Poster 361.

    • van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB. Longterm safety of rituximab: final report of the rheumatoid arthritis global clinical trial program over 11 years. J Rheumatol. 2015;42(10):1761-1766.

      van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB. Longterm safety of rituximab: final report of the rheumatoid arthritis global clinical trial program over 11 years. J Rheumatol. 2015;42(10):1761-1766.

    • Data on file, DANCER Trial CSR. Genentech USA, Inc.

      Data on file, DANCER Trial CSR. Genentech USA, Inc.

    • Data on file, REFLEX Trial CSR. Genentech USA, Inc.

      Data on file, REFLEX Trial CSR. Genentech USA, Inc.

    • Data on file, FDA approval letter, 02/2006. Genentech USA, Inc.

      Data on file, FDA approval letter, 02/2006. Genentech USA, Inc.

    • Data on file, Label update approval letter, 01/2008. Genentech USA, Inc.

      Data on file, Label update approval letter, 01/2008. Genentech USA, Inc.

    • Data on file, Label update approval letter, 10/2009. Genentech USA, Inc.

      Data on file, Label update approval letter, 10/2009. Genentech USA, Inc.

    • Data on file, FDA approval letter, 04/2011. Genentech USA, Inc.

      Data on file, FDA approval letter, 04/2011. Genentech USA, Inc.

    • Data on file, Label update approval letter, 09/2019. Genentech USA, Inc.

      Data on file, Label update approval letter, 09/2019. Genentech USA, Inc.

    • Brogan P, Cleary G, Hersh AO, et al. Presented at the 2018 American College of Rheumatology/American College of Rheumatology Health Professionals Annual Meeting: October 19-24, 2018; Chicago, IL. Poster Abstract L04.

      Brogan P, Cleary G, Hersh AO, et al. Presented at the 2018 American College of Rheumatology/American College of Rheumatology Health Professionals Annual Meeting: October 19-24, 2018; Chicago, IL. Poster Abstract L04.

    • Data on file, BLA Integrated Summary of Safety.

      Data on file, BLA Integrated Summary of Safety.