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Rituxan (Rituximab) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The most serious adverse reactions caused by RITUXAN include infusion reactions, tumor lysis syndrome, mucocutaneous reactions, hypersensitivity reactions, cardiac arrhythmias and angina, and renal failure. Please refer to the BOX WARNINGS and WARNINGS sections for detailed descriptions of these reactions. Infusion reactions and lymphopenia are the most commonly occurring adverse reactions.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Additional adverse reactions have been identified during postmarketing use of RITUXAN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to RITUXAN exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to RITUXAN.

Where specific percentages are noted, these data are based on 356 patients treated in nonrandomized, single-arm studies of RITUXAN administered as a single agent. Most patients received RITUXAN 375 mg/m2 weekly for 4 doses. These include 39 patients with bulky disease (lesions >/= 10 cm) and 60 patients who received more than 1 course of RITUXAN. Thirty-seven patients received 375 mg/m2 for 8 doses and 25 patients received doses other than 375 mg/m2 for 4 doses and up to 500 mg/m2 single dose in the Phase 1 setting. Adverse events of greater severity are referred to as "Grade 3 and 4 events" defined by the commonly used National Cancer Institute Common Toxicity Criteria. 17

Table 3
Incidence of Adverse Events >/= 5% of Patients in Clinical
Trials (N = 356) (Adverse Events were followed for a period of 12 months following RITUXAN therapy)
   All Grades (%) Grade 3 and 4 (%)
Any Adverse Events 99 57
Body as a Whole 86 10
   Fever 53 1
   Chills 33 3
   Infection 31 4
   Asthenia 26 1
   Headache 19 1
   Abdominal Pain 14 1
   Pain 12 1
   Back Pain 10 1
   Throat Irritation 9 0
   Flushing 5 0
Cardiovascular System 25 3
   Hypotension 10 1
   Hypertension 6 1
Digestive System 37 2
   Nausea 23 1
   Diarrhea 10 1
   Vomiting 10 1
Hemic and Lymphatic System 67 48
   Lymphopenia 48 40
   Leukopenia 14 4
   Neutropenia 14 6
   Thrombocytopenia 12 2
   Anemia 8 3
Metabolic and Nutritional Disorders 38 3
   Angioedema 11 1
   Hyperglycemia 9 1
   Peripheral Edema 8 0
   LDH Increase 7 0
Musculoskeletal System 26 3
   Myalgia 10 1
   Arthralgia 10 1
Nervous System 32 1
   Dizziness 10 1
   Anxiety 5 1
Respiratory System 38 4
   Increased Cough 13 1
   Rhinitis 12 1
   Bronchospasm 8 1
   Dyspnea 7 1
   Sinusitis 6 0
Skin and Appendages 44 2
   Night Sweats 15 1
   Rash 15 1
   Pruritus 14 1
   Urticaria 8 1

Risk Factors Associated with Increased Rates of Adverse Events:    Administration of RITUXAN weekly for 8 doses resulted in higher rates of Grade 3 and 4 adverse events17 overall (70%) compared with administration weekly for 4 doses (57%). The incidence of Grade 3 or 4 adverse events was similar in patients retreated with RITUXAN compared with initial treatment (58% and 57%, respectively). The incidence of the following clinically significant adverse events was higher in patients with bulky disease (lesions >/=10 cm) (N = 39) versus patients with lesions < 10 cm (N = 195): abdominal pain, anemia, dyspnea, hypotension, and neutropenia.

Infusion Reactions (See BOX WARNINGS and WARNINGS):    Mild to moderate infusion reactions consisting of fever and chills/rigors occurred in the majority of patients during the first RITUXAN infusion. Other frequent infusion reaction symptoms included nausea, pruritus, angioedema, asthenia, hypotension, headache, bronchospasm, throat irritation, rhinitis, urticaria, rash, vomiting, myalgia, dizziness, and hypertension. These reactions generally occurred within 30 to 120 minutes of beginning the first infusion, and resolved with slowing or interruption of the RITUXAN infusion and with supportive care (diphenhydramine, acetaminophen, IV saline, and vasopressors). In an analysis of data from 356 patients with relapsed or refractory, low-grade NHL who received 4 (N = 319) or 8 (N = 37) weekly infusions of RITUXAN, the incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion (30% with fourth infusion and 14% with eighth infusion).

Infectious Events:    RITUXAN induced B-cell depletion in 70% to 80% of patients and was associated with decreased serum immunoglobulins in a minority of patients; the lymphopenia lasted a median of 14 days (range, 1 to 588 days). Infectious events occurred in 31% of patients: 19% of patients had bacterial infections, 10% had viral infections, 1% had fungal infections, and 6% were unknown infections. Incidence is not additive because a single patient may have had more than one type of infection. Serious infectious events (Grade 3 or 4),17 including sepsis, occurred in 2% of patients.

Hematologic Events:    In clinical trials, Grade 3 and 4 cytopenias17 were reported in 48% of patients treated with RITUXAN; these include: lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1 to 588 days) and of neutropenia was 13 days (range, 2 to 116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following RITUXAN therapy were reported.

In addition, there have been a limited number of postmarketing reports of prolonged pancytopenia, marrow hypoplasia, and late onset neutropenia (defined as occurring 40 days after the last dose of RITUXAN) in patients with hematologic malignancies. In reported cases of late onset neutropenia (NCI-CTC Grade 3 and 4), the median duration of neutropenia was 10 days (range 3 to 148 days). Documented resolution of the neutropenia was described in approximately one-half of the reported cases; of those with documented recovery, approximately half received growth factor support. In the remaining cases, information on resolution was not provided. More than half of the reported cases of delayed onset neutropenia occurred in patients who had undergone a prior autologous bone marrow transplantation. In an adequately designed, controlled, clinical trial, the reported incidence of NCI-CTC Grade 3 and 4 neutropenia was higher in patients receiving RITUXAN in combination with fludarabine as compared to those receiving fludarabine alone (76% [39/51] vs. 39% [21/53]). 18

Cardiac Events (See BOX WARNINGS):    Grade 3 or 4 cardiac-related events include hypotension. Rare, fatal cardiac failure with symptomatic onset weeks after RITUXAN has also been reported. Patients who develop clinically significant cardiopulmonary events should have RITUXAN infusion discontinued.

Pulmonary Events (See BOX WARNINGS):    135 patients (38%) experienced pulmonary events in clinical trials. The most common respiratory system adverse events experienced were increased cough, rhinitis, bronchospasm, dyspnea, and sinusitis. In both clinical studies and post-marketing surveillance, there have been a limited number of reports of bronchiolitis obliterans presenting up to 6 months post-RITUXAN infusion and a limited number of reports of pneumonitis (including interstitial pneumonitis) presenting up to 3 months post-RITUXAN infusion, some of which resulted in fatal outcomes. The safety of resumption or continued administration of RITUXAN in patients with pneumonitis or bronchiolitis obliterans is unknown.

Immune/Autoimmune Events: Immune/autoimmune events have been reported, including uveitis, optic neuritis in a patient with systemic vasculitis, pleuritis in a patient with a lupus-like syndrome, serum sickness with polyarticular arthritis, and vasculitis with rash.

Less Commonly Observed Events:    In clinical trials, < 5% and > 1% of the patients experienced the following events regardless of causality assessment: agitation, anorexia, arthritis, conjunctivitis, depression, dyspepsia, edema, hyperkinesia, hypertonia, hypesthesia, hypoglycemia, injection site pain, insomnia, lacrimation disorder, malaise, nervousness, neuritis, neuropathy, paresthesia, somnolence, vertigo, weight decrease.



REPORTS OF SUSPECTED RITUXAN SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Rituxan. The information is not vetted and should not be considered as verified clinical evidence.

Possible Rituxan side effects / adverse reactions in 81 year old female

Reported by a physician from United States on 2011-10-12

Patient: 81 year old female weighing 72.0 kg (158.4 pounds)

Reactions: Progressive Multifocal Leukoencephalopathy, Convulsion

Suspect drug(s):
Rituxan
    Dosage: rituxan weekly ivss; rituxan weekly ivss
    Start date: 2011-07-20

Rituxan
    Dosage: rituxan weekly ivss; rituxan weekly ivss
    Start date: 2011-07-27



Possible Rituxan side effects / adverse reactions in 86 year old male

Reported by a physician from United States on 2011-10-17

Patient: 86 year old male

Reactions: Progressive Multifocal Leukoencephalopathy

Suspect drug(s):
Rituxan

Other drugs received by patient: Vincristine; Prednisone; Cyclophosphamide; Doxorubicin HCL



Possible Rituxan side effects / adverse reactions in 81 year old female

Reported by a physician from United States on 2011-10-17

Patient: 81 year old female

Reactions: Progressive Multifocal Leukoencephalopathy

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Rituxan



See index of all Rituxan side effect reports >>

Drug label data at the top of this Page last updated: 2006-10-18

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