Rituxan for GPA and MPA Administration Tear Pad

The Tear Pad is multiple resources in one. It contains a Patient Checklist of important medical history questions, a Preparation Worksheet to complete in advance of administration, and an Infusion Flow Sheet to document patient vitals during each infusion.

INDICATION

  • Rituxan® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)

BOXED WARNINGS and Additional Important Safety Information

BOXED WARNINGS

Infusion Reactions: Rituxan administration can result in serious, including fatal infusion 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 reactions.

Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan. 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.

Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving Rituxan. 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. 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: 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). 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 vaccines is not recommended before or during treatment.

Embryo-Fetal Toxicity: Rituxan can cause fetal harm due to B-cell lymphocytopenia in infants exposed to Rituxan in-utero. Advise pregnant women of the risk to a fetus. Females of childbearing potential should use effective contraception while receiving Rituxan and for 12 months following the last dose of Rituxan.

Concomitant Use With Biologic Agents and DMARDs Other Than Methotrexate: 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 Rituxan.

Retreatment in Patients with Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA): Limited data are available on the safety and efficacy of subsequent courses of Rituxan in patients with GPA and MPA. The safety and efficacy of retreatment with Rituxan have not been established.

Adverse Reactions

Clinical Trials Experience in GPA and MPA

Adverse reactions reported in ≥15% of Rituxan-treated patients vs cyclophosphamide-treated patients were infections (62% vs 47%), nausea (18% vs 20%), diarrhea (17% vs 12%), headache (17% vs 19%), muscle spasms (17% vs 15%), anemia (16% vs 20%), and peripheral edema (16% vs 6%), respectively.

Infusion Reactions: In the active-controlled, double-blind study, 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 reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion reactions.

Infections: In the active-controlled, double-blind study, 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. 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.

Immunogenicity
A total of 23/99 (23%) Rituxan-treated patients with GPA or MPA tested positive for anti-rituximab antibodies by 18 months. The clinical relevance of anti-rituximab antibody formation in Rituxan-treated patients is unclear.

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

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

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

 
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