Rituximab
Rituximab Uses, Dosage, Side Effects, Food Interaction and all others data.
Rituximab is a chimeric monoclonal antibody to CD20 antigen which regulates cell cycle initiation. It binds to the antigen on the cell surface, activating complement-dependent B-cell cytotoxicity; and to human Fc receptors, mediating cell killing through an antibody-dependent cellular toxicity.
Duration: Detectable in serum 3-6 mth after completion of therapy; B-cell recovery 6-12 mth following completion of therapy.
Rituximab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lymphomas . The antibody leads to selective killing of B-cells. The following are the pharmacodynamic outcomes for various conditions, including non- Hodgkin's Lymphoma :
Non-Hodgkin’s Lymphoma (NHL)In Non-Hodgkin's Lymphoma patients, the administration of rituximab led to the depletion of circulating and tissue-based B cells. Among 166 patients in Study 1, circulating CD19-positive B cells were depleted within the first three weeks, showing sustained depletion for up to 6-9 months post-treatment in 83% of treated patients. B-cell recovery began at approximately 6 months and median B-cell levels returned to normal by 12 months following the completion of treatment . There were sustained and statistically significant decreases in serum IgM and IgG levels measured from 5-11 months following rituximab administration; 14% of patients showed IgM and/or IgG serum levels below the normal range .
Rheumatoid ArthritisIn rheumatoid arthritis (RA) patients, treatment with rituximab induced the depletion of peripheral B lymphocytes, with the majority of patients showing near-complete depletion (CD19 counts below the lower limit of quantification, 20 c-lls/μl) within 2 weeks after the first dose of rituximab. The majority of treated patients showed peripheral B-cell depletion, sustained for a minimum of 6 months. A small percentage of patients (~4%) had peripheral B-cell depletion that was sustained for more than 3 years after one course of treatment. Total serum immunoglobulin levels, IgM, IgG, and IgA were decreased at 6 months with the greatest change observed in IgM. At Week 24 of the first cycle of rituximab treatment, small percentages of patients experienced decreases in IgM (10%), IgG (2.8%), and IgA (0.8%) levels below the lower limit of normal (LLN). When rituximab was administered to RA patients during repeated rituximab treatment, 23.3%, 5.5%, and 0.5% of patients experienced decreases in IgM, IgG, and IgA concentrations below LLN at any time after receiving rituximab, respectively. The clinical consequences of decreases in immunoglobulin levels in RA patients treated with rituximab are not clear at this time. Treatment with rituximab in patients with RA was associated with a decreased level of several biologic markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid protein (SAA), S100 A8/S100 A9 heterodimer complex (S100 A8/9), anti-citrullinated peptide (anti-CCP), and RF and was found to decrease disease symptoms .
| Trade Name | Rituximab |
| Availability | Prescription only |
| Generic | Rituximab |
| Rituximab Other Names | Rituximab, rituximab-abbs, rituximab-arrx, rituximab-pvvr |
| Related Drugs | Calquence, Truxima, Gazyva, Zydelig, Tecartus, Humira, Venclexta, prednisone, methotrexate, hydroxychloroquine |
| Weight | 10mg/ml, abbs10mg/ml, arrx10mg/ml, pvvr10mg/ml, |
| Type | Intravenous Solution, Intravenous |
| Formula | C6416H9874N1688O1987S44 |
| Weight | 143859.7 Da |
| Groups | Approved |
| Therapeutic Class | Cytotoxic immunosuppressants |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Non-Hodgkin's Lymphoma (NHL): Rituximab is used for the treatment of patients with-
- Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
- Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy.
- Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line CVP chemotherapy
- Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
Chronic Lymphocytic Leukemia (CLL): Rituximab is used, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL.
Rheumatoid Arthritis (RA): Rituximab in combination with methotrexate is used for the treatment of adult patients with moderately- to severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.
Granulomatos Is With Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA): Rituximab, in combination with glucocorticoids, is used for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) andMicroscopic Polyangiitis (MPA).
Rituximab is also used to associated treatment for these conditions: Chronic Lymphocytic Leukaemia (CLL), Granulomatosis With Polyangiitis, Granulomatosis With Polyangiitis (GPA), Microscopic Polyangiitis, Microscopic Polyangiitis (MPA), Non-Hodgkin's Lymphoma (NHL), Pemphigus Vulgaris (PV), Moderate Rheumatoid arthritis, Moderate to severe pemphigus vulgaris, Severe Rheumatoid arthritis
How Rituximab works
Rituximab is a monoclonal antibody that targets the CD20 antigen, which is expressed on the surface of pre-B and mature B-lymphocytes , , , . After binding to CD20, rituximab mediates B-cell lysis (or breakdown). The possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) .
Rituximab belongs to the immunoglobulin G1 (IgG1) sub-class, consisting of a murine variable region (Fab region) and a human constant region (Fc region). The Fab region has variable sections that define a specific target antigen, allowing the antibody to attract and secure its exclusive antigen, specifically the binding of rituximab (IgG1) to CD20 on pre-B and mature B lymphocytes. The Fc region is the tail end of the antibody that communicates with cell surface receptors to activate the immune system, in this case, a sequence of events leading to the depletion of circulating B lymphocytes by complement-dependent cell lysis, antibody-dependent cellular cytotoxicity, as well as apoptosis .
In regards to the mechanism of action in rheumatoid arthritis, B cells are thought to play a role in the pathogenesis of rheumatoid arthritis (RA) and the associated condition of chronic synovitis. B cells may act at various sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or the production of proinflammatory cytokines . The administration of rituximab in this condition has been shown to result in significant clinical and symptomatic improvements , .
Dosage
Rituximab dosage
Intravenous (Adult)-
Non-Hodgkin's lymphoma, Refractory or relapsed follicular lymphoma: As a single agent, 375 mg/m2 infusion once wkly, for 4 doses at an initial rate of 50 mg/hr. May increase by 50 mg/hr every 30 min. If tolerated, subsequent infusions can be started at 100 mg/hr and increased by 100 mg/hr every 30 min. Max rate: 400 mg/hr. When used with CVP (cyclophosphamide, vincristine and prednisolone) for follicular lymphoma or CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) for diffuse large B-cell lymphoma, 375 mg/m2 given on day 1 of the chemotherapy cycle after corticosteroid regimen, for up to 8 cycles. For patients who were treated with 6-8 cycles of CVP chemotherapy and have not progressed, 375 mg/m2 may be given once wkly for 4 doses, may repeat every 6 mth, for up to 16 doses. Maintenance: 375 mg/m2 given once every 3 mth (those who have responded to induction chemotherapy), once every 2 mth initiated 2 mth after the last dose of induction chemotherapy (previously untreated) for a max period of 2 yr.
Chronic lymphocytic leukaemia: 375 mg/m2, given on the day prior to chemotherapy in cycle 1, followed by 500 mg/m2 on day 1 (every 28 days) of cycles 2-6.
Rheumatoid arthritis: Given as two 1 g IV infusion doses, separated by 2 wk and in combination with methotrexate. Corticosteroids may be given before each infusion to minimise the risk and severity of infusion reactions.
Dilute the appropriate dose with sodium chloride 0.9% or glucose 5% to a final concentration of between 1 and 4 mg/mL.
Side Effects
Reactivation of hepatitis B virus. Fever and rigors. Pruritus, skin rashes, dyspnoea, bronchospasm, angioedema, transient hypotension, and flushing, asthenia, headache, rhinitis, thrombocytopenia, neutropenia, anaemia, abdominal pain, bowel obstruction, and perforation. Exacerbation of heart failure and angina pectoris. Reversible interstitia
Toxicity
Oral LD50: 27 mg/kg (mouse and rat)
Inhalation LD50: 32 mg/m3 (mouse) and 37 mg/m3 (rat)
Skin LD50: 20 mg/kg (rabbit) and 50 mg/kg (rat)
Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of rituximab or to determine potential effects on fertility in males or females .
Embryo-Fetal toxicity: Can cause neonatal harm. Advise of potential risk to neonates and use of effective contraception .
Precaution
Extensive tumour burden, pulmonary insufficiency or pulmonary tumour infiltration; history of cardiac disease. Pregnancy.
Interaction
Increased risk of renal toxicity with cisplatin.
Food Interaction
No interactions found.Rituximab Drug Interaction
Unknown: sulfamethoxazole / trimethoprim, diphenhydramine, celecoxib, mycophenolate mofetil, docusate, duloxetine, apixaban, omega-3 polyunsaturated fatty acids, furosemide, pregabalin, polyethylene glycol 3350, esomeprazole, acetaminophen, hydroxychloroquine, budesonide / formoterol, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol
Rituximab Disease Interaction
Major: autoimmune diseases, cardiac dysfunction, hepatitis B, TLSModerate: bone marrow suppression, infections, renal impairment
Volume of Distribution
3.1 L in Rheumatoid Arthritis
4.5 L in Granulomatosis with polyangitis and microscopic polyangitis
Elimination Route
Following the administration of 2 doses of rituximab in patients with rheumatoid arthritis (RA), the mean (± S.D.; % CV) concentrations after the first infusion (Cmax first) and second infusion (Cmax second) were : 157 ( ± 46; 29%) and 183 ( ± 55; 30%) mcg/mL, and 318 ( ± 86; 27%) and 381 ( ± 98; 26%) mcg/mL for the 2 × 500 mg and 2 × 1000 mg doses, respectively .
Half Life
Non-Hodgkin's Lymphoma: Based on a population pharmacokinetic analysis of data from 298 Non-Hodgkin's Lymphoma (NHL) patients who received rituximab once weekly or once every three weeks, the estimated median terminal elimination half-life was 22 days (range, 6.1 to 52 days) .
Rheumatoid Arthritis: Mean terminal elimination half-life was 18.0 days in patients with rheumatoid arthritis Based on a population pharmacokinetic analysis of data from 2005 RA patients who received rituximab .
Chronic Lymphocytic Leukemia (CLL): Pharmacokinetics were studied in 21 patients with CLL receiving rituximab according to the recommended dose and schedule. The estimated median terminal half-life of rituximab was 32 days (range, 14-62 days) .
Granulomatosis with Polyangitis and Microscopic Polyangitis: Based on the population pharmacokinetic analysis of data in 97 GPA and MPA patients who received 375 mg/m2 rituximab once weekly by intravenous infusion for four weeks, the estimated median terminal elimination half-life was 23 days (range, 9 to 49 days) .
Clearance
Rheumatoid Arthritis: 0.335 L/day
Granulomatosis with Polyangitis and Microscopic Polyangitis: 0. 312 L/day
Patients with higher CD19-positive cell counts or larger measurable tumor lesions at pretreatment had a higher clearance .
Elimination Route
Likely eliminated through the reticuloendothelial system .
Pregnancy & Breastfeeding use
Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Contraindication
Hypersensitivity to murine proteins. Patients with active, severe infections. Severely immunocompromised state. Concomitant use with live viral vaccines. Lactation.
Storage Condition
Store between 2-8° C.
Innovators Monograph
You find simplified version here Rituximab
Rituximab contains Rituximab see full prescribing information from innovator Rituximab Monograph, Rituximab MSDS, Rituximab FDA label
FAQ
What is Rituximab used for?
Rituximab used alone or with other medications to treat various types of non-Hodgkin's lymphoma, a type of cancer that begins in a type of white blood cells that normally fights infection.
How safe is Rituximab?
Over 540,000 patients worldwide have now received Rituximab and serious adverse reactions have occurred in a small minority of patients, but for the great majority of patients, Rituximab is safe and well tolerated.
How does Rituximab work?
Rituximab work by helping your own immune system destroy the cancer cells. By destroying the cancer cells on its own.
What are the common side effects of Rituximab?
Common side effects of Rituximab include:
- headache,
- fever,
- chills,
- stomach pain,
- nausea,
- diarrhea,
- heartburn,
- flushing,
- night sweats,
- weakness,
- muscle or joint pain,
- back pain, or
- dizziness.
Is Rituximab safe during pregnancy?
Rituximab may not be completely safe during pregnancy and should be stopped at least 12 months before attempting to conceive. Rituximab may be used in early pregnancy for exceptional cases, but it should be avoided in the last trimester.
Is Rituximab safe during breastfeeding?
Rituximab is barely detected in breast milk of women with relapsing-remitting multiple sclerosis who took the therapy while breastfeeding their child, small study shows. Results suggest that women with RRMS can continue with a disease-modifying treatment while breastfeeding.
Can I drink alcohol with Rituximab?
You can drink alcohol while on Rituximab, but you should keep within the recommended limits for adults of no more than 14 units per week.
Does Rituximab affect sleep?
Rituximab can affect the nervous system. You may feel anxious or restless, have problems sleeping or feel dizzy.
Can I drive after taking Rituximab?
It is not recommended that you drive any motor vehicle for up to 24 hours following a dose of Rituximab.
How many times can Rituximab be given?
Administer Rituximab as a single-agent every 8 weeks for 12 doses. Following completion of 6−8 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses.
Does Rituximab lower immune system?
Rituximab suppresses the immune system.
How long can you be on Rituximab?
Rituximab can provide up to 6 months of symptom improvement from 1 course of treatment .
How long does Rituximab take to work?
Rituximab takes about 4-6 weeks to work and depending on your renal disease, your other immunosuppressant drugs need to be continued for 4-8 weeks, or stopped on the first dose. The effect of Rituximab usually lasts for between six and nine months.
Can Rituximab cause kidney damage?
Rituximab can cause severe kidney problems that lead to death.
Does Rituximab affect memory?
Rituximab may cause memory problems, confusion, sight loss and difficulty walking.
Does Rituximab affect the heart?
It is advised that Rituximab infusion may cause infusion reactions and adverse cardiac effects including arrhythmia and angina, especially in patients with prior history of cardiovascular diseases.
Does Rituximab affect the liver?
Rituximab has been linked to many cases of severe and even fatal liver injury as a result of reactivation of inactive or previously resolved hepatitis B.
Can Rituximab cause lung problems?
Rituximab induced lung disease is a rare but potentially fatal pulmonary toxicity which requires a high index of suspicion for early diagnosis and treatment.
Does Rituximab cause joint pain?
Brand can cases joint pain also with other side effects.
Will Rituximab affect my fertility?
Rituximab has not known to cause infertility and appears to be a safe and effective alternative. The use of Rituximab before pregnancy is well tolerated. It is advised to stop the drug 12 months before attempting to conceive.
What Happens If I stop taking Rituximab?
This could lead to liver failure or even death. The risk continues for more than a month after you stop taking Rituximab. If you become jaundiced Rituximab or develop viral hepatitis while taking Rituximab, you should tell your doctor immediately.
What happens if I miss a dose of Rituximab?
Contact your physician immediately if you miss a dose of Rituximab. Your health-care professional will be able to assist you in rescheduling your appointment or determining another way to handle the missed dose.
What happens if I overdose?
Since Rituximab is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.
