Safety Profile
Rituxan has an established safety profile
In controlled RA clinical trials with Rituxan5:
- No treatment-emergent tuberculosis has been observed
- No hematologic malignancies (lymphomas) have been reported
- Low incidence of opportunistic infections
- Observed rate of malignancies was consistent with the rate observed in a similar RA population
- Existing antibody titers against mumps, rubella, varicella, tetanus toxoid, influenza, and pneumococcus remained stable over 6 months
Incidence of adverse events >2%, and at least 1% greater with Rituxan
| Most common adverse events in RA clinical trials up to month 62,a | Rituxan + MTX (n=540) | Placebo + MTX (n=398) |
|---|---|---|
| Hypertension | 8% | 5% |
| Nausea | 8% | 5% |
| Upper respiratory tract infection | 7% | 6% |
| Arthralgia | 6% | 4% |
| Pyrexia | 5% | 2% |
| Pruritus | 5% | 1% |
| Chills | 3% | 2% |
| Rhinitis | 3% | 2% |
| Dyspepsia | 3% | <1% |
| Upper abdominal pain | 2% | 1% |
| Migraine | 2% | <1% |
| Anxiety | 2% | 1% |
| Asthenia | 2% | <1% |
| Hypercholesterolemia | 2% | <1% |
| Paresthesia | 2% | <1% |
| Urticaria | 2% | <1% |
| Throat irritation | 2% | 0 |
aCoded using MedDRA.
These data are based on 938 patients treated in phase 2 and phase 3 studies of Rituxan (2 x 1000 mg) or placebo administered in combination with methotrexate.
Adapted from Rituxan full prescribing information.2
Additional Infection information
- In RA clinical studies, 39% of patients in the RITUXAN group experienced an infection of any type compared to 34% for placebo. The most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis.
- The incidence of serious infections was 2% in the RITUXAN patients and 1% in the placebo group. One fatal infection (bronchopneumonia) occurred with rituximab monotherapy during the 24-weeks placebo-controlled period in one of the Phase 2 RA studies.
- In 107 Rituxan-treated RA patients with active disease, subsequent treatment with a TNF inhibitor was associated with a higher rate of serious infections. Six serious infections were observed in 100.8 patient years (0.06 per patient year) prior to exposure and 9 were observed in 97.8 patient years (0.09 per patient year) after exposure.
27% of patients in clinical trials experienced acute infusion reactions; less than 1% were serious2
All infusion reactions were manageable, with the majority categorized as mild in clinical trials5
Data derived from Rituxan full prescribing information.2
- By the second infusion, the rate of infusion reactions was comparable with placebo2
- 10% of the patients in the group receiving Rituxan had acute infusion reactions requiring stopping, slowing, or interruption of the infusion during the first course, vs 2% of patients in the placebo group2
- Most infusion reaction adverse events were managed supportively by decreasing the rate of or temporarily stopping the infusion, and/or giving an antihistamine or corticosteroid5
No fatal infusion reactions have been reported to date in Rituxan-treated RA patients5
Important Safety Information
WARNINGS
Severe infusion reactions: RITUXAN can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30 to 120 minutes. Rituxan-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, or anaphylactoid events. Interrupt the infusion for severe reactions.
Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or autoimmune diseases for which Rituxan has not been approved. 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 a history of prior,or concurrent, immunosuppressive therapy and were diagnosed with PML within 12 months of their last infusion of Rituxan.
Hepatitis B Reactivation with Related Fulminant Hepatitis: Persons at high risk of HBV infection should be screened before initiation of RITUXAN.
Cardiovascular: 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.
Immunization: The safety of immunization with live viral vaccines following RITUXAN therapy has not been studied and vaccination with live vaccines are not recommended in patients receiving RITUXAN.
Concomitant use with biologic agents and DMARDs other than methotrexate in RA: Limited data are available on the safety of the use of biologic agents or DMARDs other than methotrexate in patients exhibiting peripheral B cell depletion following treatment with rituximab. Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly.
Use in patients with RA who had no prior inadequate response to TNF antagonists: The use of RITUXAN in patients with RA who have no prior inadequate response to one or more TNF antagonists is not recommended.
Retreatment of patients with RA: Safety and efficacy of retreatment have not been established in controlled trials. A limited number of patients have received two to five courses (two infusions per course) of treatment in an uncontrolled setting.
Adverse Effects
The most common adverse events with greater incidence in the group receiving RITUXAN (n=540) vs. the placebo group (n=398) 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%). These data are based on 938 patients treated in Phase 2 and 3 studies of RITUXAN (2 x 1000 mg) or placebo administered in combination with methotrexate.
Infusion Reactions: In RA studies, 32% of RITUXAN patients experienced an adverse event during or within 24 hours following their first infusion, compared to 23% for placebo. This decreased to11% and 13%, respectively following the second infusion. Acute infusion reactions (manifested by fever, chills, rigors, pruritus, urticaria/rash, angioedema, sneezing, throat irritation, cough, and/or bronchospasm, with or without associated hypotension or hypertension) were experienced by 27% of RITUXAN patients following their first infusion, compared to 19% for placebo. These acute infusion reactions decreased to 9% and 11%, respectively. Serious acute infusion reactions were experienced by <1% of patients in either treatment group.
Infections: In RA clinical studies, 39% of patients in the RITUXAN group experienced an infection of any type compared to 34% for placebo. The most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis.
The incidence of serious infections was 2% in the RITUXAN patients and 1% in the placebo group. One fatal infection (bronchopneumonia) occurred with rituximab monotherapy during the 24-weeks placebo-controlled period in one of the Phase 2 RA studies.
In 107 Rituxan-treated RA patients with active disease, subsequent treatment with a TNF inhibitor was associated with a higher rate of serious infections. Six serious infections were observed in 100.8 patient years (0.06 per patient year) prior to exposure and 9 were observed in 97.8 patient years (0.09 per patient year) after exposure.
Cardiac Events: The incidence of serious cardiovascular events in the double-blind part of the clinical trials were 1.7% and 1.3% in RITUXAN and placebo treatment groups, respectively. Three cardiovascular deaths occurred during the double-blind period of the RA studies including all rituximab regimens (3/769 = 0.4%) as compared to none in the placebo treatment group (0/389).
Hypophosphatemia and hyperuricemia: In the 24 week double-blind RA clinical trial program, newly-occurring hypophosphatemia (<2.0 mg/dl) was observed in 12% (67/540) of patients on Rituxan versus 10% (39/398) of patients on placebo. Hypophosphatemia was more common in patients who received corticosteroids. Newly occurring hyperuricemia (>10 mg/dl) was observed in 1.5% (8/540) of patients on Rituxan versus 0.3% (1/398) of patients on placebo.
Immunogenicity: A total of 118/1053 patients (11%) with RA tested positive for HACA at any time after treatment with Rituxan. Limited data are available on the safety or efficacy of Rituxan retreatment in patients who develop HACA. Of the 8 patients who experienced serious acute infusion reactions, 2 were subsequently found to be HACA positive. Approximately 12% (14/118) of patients who were HACA-positive had a subsequent infusion reaction of any severity. The clinical relevance of HACA formation in rituximab treated patients is unclear.
ATTENTION HEALTHCARE PROVIDER: PROVIDE MEDICATION GUIDE TO PATIENT PRIOR TO RITUXAN INFUSION.
