Does Rituxan (rituximab) cause side effects?
Rituxan (rituximab) is a monoclonal antibody used to treat B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis. Rituxan also is combined with methotrexate to treat rheumatoid arthritis.
Tumor cells (like most normal cells) have receptors on their surfaces. Many kinds of chemicals, proteins, etc., on the outside of the cell can attach to these receptors. When they do, they can cause changes to occur within the cells.
One receptor called CD20 is present in more than 90% of B-cell non-Hodgkin's lymphomas. Molecules that attach to CD20 can affect the growth and development of the tumor cells and the production of new tumor cells. Rituximab is thought to attach to the CD20 receptor and cause tumor cells to disintegrate.
In some non-Hodgkin's lymphomas, it also prevents the production of more tumor cells. In the treatment of rheumatoid arthritis, its effectiveness is a result of it temporarily depleting the number of B-cells, cells of the immune system important in promoting inflammation in rheumatoid arthritis.
Common side effects of Rituxan include
Other side effects of Rituxan include
- difficulty breathing,
- a sensation of swelling of the tongue or throat,
- runny nose,
- decreased blood pressure,
- flushing, and
- pain at the site of the tumor.
Serious side effects of Rituxan include
- tumor lysis syndrome,
- irregular heart rhythms,
- severe decreases in red or white blood cells and platelets (thrombocytopenia);
- serious fungal, bacterial, and new or reactivated viral infections (for example, hepatitis B or C, shingles); and
- severe skin reactions within 1 to 13 weeks after treatment is started.
Drug interactions of Rituxan include
- cisplatin or amphotericin B because it increases the risk of kidney failure.
The combination of certolizumab pegol with Rituxan may increase immune suppression and risk of infections.
There are not enough studies to draw conclusions about the safety of Rituxan in pregnant women. Contraception is recommended if Rituxan is used in women of childbearing age and for up to 12 months after stopping therapy.
Since Rituxan is an antibody that can be secreted into breast milk and absorbed by the infant, it has the potential to harm nursing infants. Women who are breastfeeding should avoid Rituxan therapy and not begin nursing until Rituxan is no longer present in the blood.
What are the important side effects of Rituxan (rituximab)?
- The most common side effect of rituximab is a constellation of symptoms (fever, rigors and chills) that occur during administration of the first dose of drug.
- More than 80% of patients experience these side effects, and it is severe in 4-7 out of every 10,000 patients.
- The side effects appear only 40% of the time with the second dose of drug and become less frequent with the last two doses.
Other common side effects related to rituximab are
- Difficulty breathing due to bronchospasm
- A sensation of swelling of the tongue or throat
- Runny nose
- Decreased blood pressure
- Pain at the site of the tumor
After rituximab is administered, large numbers of tumor cells are immediately destroyed (lysed) and eliminated from the body.
In 4-5 out of every 10,000 patients the products from the dead cells cannot be eliminated quickly enough and a syndrome called tumor lysis syndrome occurs. This is characterized by a rapid decline in kidney function and a sudden accumulation or decrease in minerals such as potassium, calcium and phosphate to dangerous levels.
Tumor lysis syndrome occurs when the size of the tumor or the number of tumor cells circulating in the blood is large, usually within 12-24 hours after the first dose of rituximab.
- Irregular heart rhythms and infection are two other rarely-occurring side effects that may be severe.
- The irregular heart rhythm usually begins soon after the administration of the drug, while infection may develop from 30 days to 11 months after the end of therapy.
- Severe decreases in red or white blood cells and platelets (thrombocytopenia) may occur rarely with rituximab therapy. Rituximab suppresses the immune system.
- Therefore, serious fungal, bacterial, and new or reactivated viral infections (for example, hepatitis B or C, shingles) can occur during or after treatment with rituximab.
- Generally, rituximab is avoided in the presence of active, significant infections.
- Rituximab may also cause severe skin reactions within 1 to 13 weeks after treatment is started.
- Rituximab therapy is not recommended if there is an allergy to mice or rats since rituximab is made in mice or rats and may contain minute amounts of rat or mice proteins that can lead to severe allergic reactions.
Rituxan (rituximab) side effects list for healthcare professionals
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
- Infusion reactions
- Severe mucocutaneous reactions
- Hepatitis B reactivation with fulminant hepatitis
- Progressive multifocal leukoencephalopathy
- Tumor lysis syndrome
- Cardiovascular adverse reactions
- Renal toxicity
- Bowel obstruction and perforation
Clinical Trials Experience In Lymphoid Malignancies
- 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 clinical practice.
- The data described below reflect exposure to Rituxan in 2783 patients, with exposures ranging from a single infusion up to 2 years.
- Rituxan was studied in both single-arm and controlled trials (n=356 and n=2427).
- The population included 1180 patients with low grade or follicular lymphoma, 927 patients with DLBCL, and 676 patients with CLL. Most NHL patients received Rituxan as an infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses.
- CLL patients received Rituxan 375 mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination with fludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy.
- The most common adverse reactions of Rituxan (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia.
- The most common adverse reactions of Rituxan (incidence ≥25%) observed in clinical trials of patients with CLL were: infusion reactions and neutropenia.
- In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion.
- Infusion reactions typically 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, and intravenous saline).
- The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion.
- In patients with previously untreated follicular NHL or previously untreated DLBCL, who did not experience a Grade 3 or 4 infusion-related reaction in Cycle 1 and received a 90-minute infusion of Rituxan at Cycle 2, the incidence of Grade 3-4 infusion-related reactions on the day of, or day after the infusion was 1.1% (95% CI [0.3%, 2.8%]). For Cycles 2-8, the incidence of Grade 3-4 infusion reactions on the day of or day after the 90-minute infusion, was 2.8% (95% CI [1.3%, 5.0%).
- Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%).
- In randomized, controlled studies where Rituxan was administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan.
Cytopenias And Hypogammaglobulinemia
- In patients with NHL receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients.
- These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1-588 days) and of neutropenia was 13 days (range, 2-116 days).
- A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies.
- In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients.
- In CLL trials, the frequency of prolonged neutropenia and late-onset neutropenia was higher in patients treated with R-FC compared to patients treated with FC.
- Prolonged neutropenia is defined as Grade 3-4 neutropenia that has not resolved between 24 and 42 days after the last dose of study treatment. Late-onset neutropenia is defined as Grade 3-4 neutropenia starting at least 42 days after the last treatment dose.
- In patients with previously untreated CLL, the frequency of prolonged neutropenia was 8.5% for patients who received R-FC (n=402) and 5.8% for patients who received FC (n=398). In patients who did not have prolonged neutropenia, the frequency of late-onset neutropenia was 14.8% of 209 patients who received R-FC and 4.3% of 230 patients who received FC.
- For patients with previously treated CLL, the frequency of prolonged neutropenia was 24.8% for patients who received R-FC (n=274) and 19.1% for patients who received FC (n=274). In patients who did not have prolonged neutropenia, the frequency of late-onset neutropenia was 38.7% in 160 patients who received R-FC and 13.6% of 147 patients who received FC.
Relapsed Or Refractory, Low-Grade NHL
- Adverse reactions presented in Table 1 occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. Most patients received Rituxan 375 mg/m2 weekly for 4 doses.
Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Low-Grade or Follicular NHL, Receiving Single-agent Rituxan (N=356)a,b
|All Grades (%)||Grade 3 and 4 (%)|
|Any Adverse Reactions||99||57|
|Body as a Whole||86||10|
|Heme and Lymphatic System||67||48|
|Skin and Appendages||44||2|
|Metabolic and Nutritional Disorders||38||3|
|a Adverse reactions observed up to 12 months following Rituxan.|
b Adverse reactions graded for severity by NCI-CTC criteria.
- In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to 6 months after Rituxan infusion.
Previously Untreated, Low-Grade Or Follicular, NHL
- In Study 4, patients in the R-CVP arm experienced a higher incidence of infusional toxicity and neutropenia compared to patients in the CVP arm. The following adverse reactions occurred more frequently (=5%) in patients receiving R-CVP compared to CVP alone:
In Study 5, detailed safety data collection was limited to serious adverse reactions, Grade ≥ 2 infections, and Grade ≥ 3 adverse reactions.
- In patients receiving Rituxan as single-agent maintenance therapy following Rituxan plus chemotherapy, infections were reported more frequently compared to the observation arm (37% vs. 22%).
- Grade 3-4 adverse reactions occurring at a higher incidence (≥ 2%) in the Rituxan group were infections (4% vs. 1%) and neutropenia (4% vs. <1%).
In Study 6, the following adverse reactions were reported more frequently (= 5%) in patients receiving Rituxan following CVP compared to patients who received no further therapy:
- fatigue (39% vs. 14%),
- anemia (35% vs. 20%),
- peripheral sensory neuropathy (30% vs. 18%),
- infections (19% vs. 9%),
- pulmonary toxicity (18% vs. 10%),
- hepato-biliary toxicity (17% vs. 7%),
- rash and/or pruritus (17% vs. 5%),
- arthralgia (12% vs. 3%), and
- weight gain (11% vs. 4%).
Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (=2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%).
In Studies 7 and 8, the following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone:
- pyrexia (56% vs. 46%),
- lung disorder (31% vs. 24%),
- cardiac disorder (29% vs. 21%), and
- chills (13% vs. 4%).
Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse reactions and serious adverse reactions.
In Study 8, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP).
The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm:
- thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%).
Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 8), neutropenia (Studies 8 and 9), and anemia (Study 9).
- The data below reflect exposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 patients with CLL in Study 11 or Study 12. The age range was 30-83 years and 71% were men. Detailed safety data collection in Study 11 was limited to Grade 3 and 4 adverse reactions and serious adverse reactions.
- Infusion-related adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea.
- In Study 11, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC-treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%).
- In Study 12, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC-treated patients compared to FC-treated patients:
- Fifty-nine percent of R-FC-treated patients experienced an infusion reaction of any severity.
Clinical Trials Experience In Rheumatoid Arthritis
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 data presented below reflect the experience in 2578 RA patients treated with Rituxan in controlled and long-term studies with a total exposure of 5014 patient-years.
- 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, patients received 2 x 500 mg or 2 x 1000 mg intravenous infusions of Rituxan or placebo, in combination with methotrexate, during a 24-week period. From these studies, 938 patients treated with Rituxan (2 x 1000 mg) or placebo have been pooled (see Table 2).
- Adverse reactions reported in ≥ 5% of patients were hypertension, nausea, upper respiratory tract infection, arthralgia, pyrexia and pruritus (see Table 2). The rates and types of adverse reactions in patients who received Rituxan 2 x 500 mg were similar to those observed in patients who received Rituxan 2 x 1000 mg.
Table 2* Incidence of All Adverse Reactions** Occurring in ≥2% and at Least 1% Greater than Placebo Among Rheumatoid Arthritis Patients in Clinical Studies Up to Week 24 (Pooled)
|Adverse Reactions||Placebo + MTX|
|Rituxan + MTX|
|Hypertension||21 (5)||43 (8)|
|Nausea||19 (5)||41 (8)|
|Upper Respiratory Tract Infection||23 (6)||37 (7)|
|Arthralgia||14 (4)||31 (6)|
|Pyrexia||8 (2)||27 (5)|
|Pruritus||5 (1)||26 (5)|
|Chills||9 (2)||16 (3)|
|Dyspepsia||3 ( < 1)||16 (3)|
|Rhinitis||6 (2)||14 (3)|
|Paresthesia||3 ( < 1)||12 (2)|
|Urticaria||3 ( < 1)||12 (2)|
|Abdominal Pain Upper||4 (1)||11 (2)|
|Throat Irritation||0 (0)||11 (2)|
|Anxiety||5 (1)||9 (2)|
|Migraine||2 ( < 1)||9 (2)|
|Asthenia||1 ( < 1)||9 (2)|
|*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.|
**Coded using MedDRA.
- In the Rituxan RA pooled placebo-controlled studies, 32% of Rituxan-treated patients experienced an adverse reaction during or within 24 hours following their first infusion, compared to 23% of placebo-treated patients receiving their first infusion.
- The incidence of adverse reactions during the 24-hour period following the second infusion, Rituxan or placebo, decreased to 11% and 13%, respectively.
- Acute infusion-related 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-treated patients following their first infusion, compared to 19% of placebo-treated patients receiving their first placebo infusion.
- The incidence of these acute infusion reactions following the second infusion of Rituxan or placebo decreased to 9% and 11%, respectively. Serious acute infusion reactions were experienced by <1% of patients in either treatment group.
- Acute infusion reactions required dose modification (stopping, slowing, or interruption of the infusion) in 10% and 2% of patients receiving rituximab or placebo, respectively, after the first course.
- The proportion of patients experiencing acute infusion reactions decreased with subsequent courses of Rituxan.
- The administration of intravenous glucocorticoids prior to Rituxan infusions reduced the incidence and severity of such reactions, however, there was no clear benefit from the administration of oral glucocorticoids for the prevention of acute infusion reactions. Patients in clinical studies also received antihistamines and acetaminophen prior to Rituxan infusions.
- In the pooled, placebo-controlled studies, 39% of patients in the Rituxan group experienced an infection of any type compared to 34% of patients in the placebo group. 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-treated patients and 1% in the placebo group.
- In the experience with Rituxan in 2578 RA patients, the rate of serious infections 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 remained 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.
- Thirteen serious infections were observed in 186.1 patient years (6.99 per 100 patient years) prior to exposure and 10 were observed in 182.3 patient years (5.49 per 100 patient years) after exposure.
Cardiovascular Adverse Reactions
- In the pooled, placebo-controlled studies, the proportion of patients with serious cardiovascular reactions was 1.7% and 1.3% in the 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).
- In the experience with Rituxan in 2578 RA patients, the rate of serious cardiac reactions was 1.93 per 100 patient years. The rate of myocardial infarction (MI) was 0.56 per 100 patient years (28 events in 26 patients), which is consistent with MI rates in the general RA population. These rates did not increase over three courses of Rituxan.
- Since patients with RA are at increased risk for cardiovascular events compared with the general population, patients with RA should be monitored throughout the infusion and 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 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.
- In the experience with Rituxan in RA patients, newly-occurring hypophosphatemia was observed in 21% (528/2570) of patients and newly-occurring hyperuricemia was observed in 2% (56/2570) of patients. The majority of the observed hypophosphatemia occurred at the time of the infusions and was transient.
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 two, three, and four 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.
Clinical Trials Experience In Granulomatosis With Polyangiitis (GPA) (Wegener’s Granulomatosis) And Microscopic Polyangiitis (MPA)
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 data presented below reflect the experience in 197 patients with GPA and MPA treated with Rituxan or cyclophosphamide in a single controlled study, which was conducted in two phases: a 6 month randomized, double-blind, double-dummy, active-controlled remission induction phase and an additional 12 month remission maintenance phase.
- In the 6-month remission induction phase, 197 patients with GPA and MPA were randomized to either Rituxan 375 mg/ m2 once weekly for 4 weeks plus glucocorticoids, or oral cyclophosphamide 2 mg/kg daily (adjusted for renal function, white blood cell count, and other factors) plus glucocorticoids to induce remission.
- Once remission was achieved or at the end of the 6 month remission induction period, the cyclophosphamide group received azathioprine to maintain remission.
- The Rituxan group did not receive additional therapy to maintain remission.
- The primary analysis was at the end of the 6 month remission induction period and the safety results for this period are described below.
Adverse reactions presented below in Table 3 were adverse events which occurred at a rate of greater than or equal to 10% in the Rituxan group. This table reflects experience in 99 GPA and MPA patients treated with Rituxan, with a total of 47.6 patient-years of observation and 98 GPA and MPA patients treated with cyclophosphamide, with a total of 47.0 patient-years of observation. Infection was the most common category of adverse events reported (47-62%) and is discussed below.
Table 3 Incidence of All Adverse Reactions Occurring in ≥ 10% of Rituxan-treated GPA and MPA Patients in the Clinical Study Up to Month 6*
|Nausea||18 (18%)||20 (20%)|
|Diarrhea||17 (17%)||12 (12%)|
|Headache||17 (17%)||19 (19%)|
|Muscle spasms||17 (17%)||15 (15%)|
|Anemia||16 (16%)||20 (20%)|
|Peripheral edema||16 (16%)||6 (6%)|
|Insomnia||14 (14%)||12 (12%)|
|Arthralgia||13 (13%)||9 (9%)|
|Cough||13 (13%)||11 (11%)|
|Fatigue||13 (13%)||21 (21%)|
|Increased ALT||13 (13%)||15 (15%)|
|Hypertension||12 (12%)||5 (5%)|
|Epistaxis||11 (11%)||6 (6%)|
|Dyspnea||10 (10%)||11 (11%)|
|Leukopenia||10 (10%)||26 (27%)|
|Rash||10 (10%)||17 (17%)|
|*The study design allowed for crossover or treatment by best medical judgment, and 13 patients in each treatment group received a second therapy during the 6 month study period.|
- Infusion-related reactions in the active-controlled, double-blind study were defined as any adverse event occurring within 24 hours of an infusion and considered to be infusion-related by investigators.
- Among the 99 patients treated with Rituxan, 12% experienced at least one infusion-related reaction, compared with 11% of the 98 patients in the cyclophosphamide group. 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 pre-medicated 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.
- In the active-controlled, double-blind study, 62% (61/99) of patients in the Rituxan group experienced an infection of any type compared to 47% (46/98) patients in the cyclophosphamide group 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% in the Rituxan-treated patients and 10% in the cyclophosphamide treated patients, with rates of approximately 25 and 28 per 100 patient-years, respectively. The most common serious infection was pneumonia.
- 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 the cyclophosphamide group.
Retreatment In Patients With GPA And MPA
- In the active-controlled, double-blind study, subsequent courses of Rituxan were allowed for patients experiencing a relapse of disease. The limited data preclude any conclusions regarding the safety of subsequent courses of Rituxan with GPA and MPA.
- As with all therapeutic proteins, there is a potential for immunogenicity.
- The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
- Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
- For these reasons, comparison of the incidence of antibodies to Rituxan in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
- Using an ELISA assay, anti-rituximab antibody was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response.
- 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 rates of infusion-related reactions or other adverse events.
- Upon further treatment, the proportions of patients with infusion 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 reactions, and the temporal relationship between anti-rituximab antibody positivity and infusion reaction was variable.
- A total of 23/99 (23%) Rituxan-treated patients with GPA and MPA tested positive for antirituximab antibodies by 18 months. The clinical relevance of anti-rituximab antibody formation in Rituxan-treated patients is unclear.
The following adverse reactions have been identified during post-approval 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 drug exposure.
- Hematologic: prolonged pancytopenia, marrow hypoplasia, Grade 3-4 prolonged or late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia, prolonged hypogammaglobulinemia.
- Cardiac: fatal cardiac failure.
- Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash.
- Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections.
- Neoplasia: disease progression of Kaposi’s sarcoma.
- Skin: severe mucocutaneous reactions.
- Gastrointestinal: bowel obstruction and perforation.
- Pulmonary: fatal bronchiolitis obliterans and fatal interstitial lung disease.
- Nervous system: Posterior Reversible Encephalopathy Syndrome (PRES) / Reversible Posterior Leukoencephalopathy Syndrome (RPLS).
What drugs interact with Rituxan (rituximab)?
Formal drug interaction studies have not been performed with Rituxan.
In patients with CLL, Rituxan did not alter systemic exposure to fludarabine or cyclophosphamide.
In clinical trials of patients with RA, concomitant administration of methotrexate or cyclophosphamide did not alter the pharmacokinetics of rituximab.
Rituxan (rituximab) is a monoclonal antibody used to treat B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis. Rituxan also is combined with methotrexate to treat rheumatoid arthritis. Common side effects of Rituxan include fever, rigors, and chills that occur during administration of the first dose of drug. Other side effects of Rituxan include nausea, hives, fatigue, headache, itching, difficulty breathing, a sensation of swelling of the tongue or throat, runny nose, vomiting, decreased blood pressure, flushing, and pain at the site of the tumor. There are not enough studies to draw conclusions about the safety of Rituxan in pregnant women. Since Rituxan is an antibody that can be secreted into breast milk and absorbed by the infant, it has the potential to harm nursing infants.
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Related Disease Conditions
Rheumatoid Arthritis (RA)
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints, the tissue around the joints, as well as other organs in the body. Early RA signs and symptoms include anemia, both sides of the body affected (symmetric), depression, fatigue, fever, joint deformity, joint pain, joint redness, joint stiffness, joint swelling, joint tenderness, joint warmth, limping, loss of joint function, loss of joint range of motion, and polyarthritis.
Leukemia is a type of cancer of the blood cells in which the growth and development of the blood cells are abnormal. Strictly speaking, leukemia should refer only to cancer of the white blood cells (the leukocytes) but in practice, it can apply to malignancy of any cellular element in the blood or bone marrow, as in red cell leukemia (erythroleukemia).
Pain Management and Rheumatoid Arthritis
Second Source article from WebMD
16 Early Rheumatoid Arthritis (RA) Signs & Symptoms
Early rheumatoid arthritis (RA) symptoms and signs vary differently from person to person. The most common body parts that are initially affected by RA include the small joints of the hands, wrists, and feet, and the knees and hip joints. Joint inflammation causes stiffness. Warmth, redness, and pain may vary in degree.
What Is Non-Hodgkin's Lymphoma?
Non-Hodgkin's lymphoma (NHL) is cancer of the lymphatic system, a vital part of the body's immune system. Symptoms include swollen lymph nodes, fever, night sweats, coughing, weakness, chest pain, unexplained weight loss, and abdominal pain.
Mantle Cell Lymphoma (MCL)
Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin's lymphoma. It is not known what causes MCL. MCL signs and symptoms include fever, enlarged spleen and liver, fatigue, and weight loss. Treatment of MCL incorporates radiotherapy and chemotherapy. MCL has a poor prognosis as it typically is diagnosed in a late stage.
What Is Burkitt Lymphoma?
There are multiple types of Burkitt lymphoma. Burkitt lymphomas are types of non-Hodgkin's lymphoma that affect the bone marrow and central nervous system. Symptoms of Burkitt lymphoma may include nausea, vomiting, headache, fatigue, enlarged lymph nodes, and many other symptoms. Diagnosis involves lab testing, imaging studies, patient history, and cytogenic evaluation. There are multiple staging systems used to stage Burkitt lymphoma. Treatment consists of chemotherapy. The prognosis tends to be more favorable in children than in adults.
Rheumatoid Arthritis vs. Fibromyalgia
Though rheumatoid arthritis (RA) and fibromyalgia have similar symptoms, RA is an autoimmune disease and fibromyalgia is a chronic pain syndrome. RA symptoms include joint redness, swelling, and pain that lasts more than 6 weeks. Fibromyalgia symptoms include widespread pain, tingling feet or hands, depression, and bowel irritability. Home remedies for both include stress reduction, exercise, and getting enough sleep.
Hodgkin's vs. Non-Hodgkin's Lymphoma
Both Hodgkin's disease (sometimes referred to as Hodgkin's lymphoma) and non-Hodgkin's lymphoma are cancers that originate in a type of white blood cell known as a lymphocyte, an important component of the body's immune system.
Rheumatoid Arthritis vs. Arthritis
Arthritis is a general term used to describe joint disease. Rheumatoid arthritis (RA) is a type of arthritis in which the body’s immune system mistakenly attacks the joints, causing chronic inflammation.
Juvenile Rheumatoid Arthritis (JRA)
Juvenile rheumatoid arthritis (JRA) annually affects one child in every thousand. There are six types of JRA. Treatment of juvenile arthritis depends upon the type the child has and should focus on treating the symptoms that manifest.
Osteoarthritis vs. Rheumatoid Arthritis
Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic joint disorders. RA is also an autoimmune disease. OA and RA symptoms and signs include joint pain, warmth, and tenderness. Over-the-counter pain relievers treat both diseases. There are several prescription medications that treat RA.
Treatment & Diagnosis
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- Chronic Myelogenous Leukemia (CML)
Medications & Supplements
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.