What is Vortuxi
Composition
Rituximab (r-DNA Origin) 500 mg, Sodium chloride I.P. 450 mg, Tri sodium citrate dihydrate I.P. 367.5 mg, Polysorbate 80 I.P.35.0 mg, Water for Injections I.P. q.s. to 50ml.
Description
Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.
The antibody is an IgG1 kappa immunoglobulin containing murine light and heavy-chain variable region sequences and human constant region sequences.Rituximab is composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids.
Undesired Effects
RA (≥10%): upper respiratory tract infection, nasopharyngitis, urinary tract infection, and bronchitis (other important adverse reactions include infusion reactions, serious infections, and cardiovascular events)
Storage Condition
Should be stored in a refrig¬erator at 2oC to 8oC. Keep the container in the outer carton in order to protect from light.
Presentation: Rituximab Injection: 500 mg Rituximab Injection 50 ml single dose vial. Each 50 ml contains 500 mg of Rituximab (10mg/ml).
Drug Interaction
Currently, there are limited data on possible drug interactions with rituximab.
In clinical trials of patients with RA, concomitant administration of methotrexate or cyclophosphamide did not alter the pharmacokinetics of rituximab.
Contraindications
Rituximab is contraindicated in patients with: Hypersensitivity to the active substance or to murine proteins, or to any of the excipients. Active, severe infections, patients in a severely immunocompromised state, Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease, Patients who have or had progressive multifocal leukoencephalopathy (PML).
Mechanism of Action
B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis via complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). The antibody induced apoptosis in the DHL 4 human B cell lymphoma cell line In this setting, B cells may be acting at multiple sites in the autoimmune/ inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production.
Indications & Dosage
Rheumatoid Arthritis: Rituximab in combination with methotrexate is indicated 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.
Recommended dose for RA: Administer rituximab as two- 1000 mg intravenous infusions separated by 2 weeks.
Glucocorticoids administered as methylprednisolone 100 mg intravenous or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions.
Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks.
Rituximab is given in combination with methotrexate.
First infusion: The recommended initial rate for infusion is 50 mg/h; after the first 30 minutes, it can be escalated in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h.
Subsequent infusions: Subsequent doses of rituximab can be infused at an initial rate of 100 mg/h, and increased by 100 mg/h increments at 30 minute intervals, to a maximum of 400 mg/h.
Special Warnings and Precautions
Tumor lysis syndrome: Administer aggressive intravenous hydration, anti-hyperuricemic agents, monitor renal function, Infections: Withhold Vortuxi and institute appropriate anti-infective therapy, Cardiac arrhythmias and angina: Discontinue infusions in case of serious or life-threatening events, Bowel obstruction and perforation: Consider and evaluate for abdominal pain, vomiting, or related symptoms, Live virus vaccines: Do not administer live virus vaccines prior to or during Vortuxi, Cytope¬nias: Monitor blood counts at regular intervals
Use in Pregnancy and Location
Pregnancy : Category C. There are no adequate and well-controlled studies of rituximab in pregnant women.
Women of childbearing potential should use effective contraception while receiving rituximab and for 12 months following treatment.
Rituximab should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lactation: It is not known whether rituximab is secreted into human milk.
However, rituximab is secreted in the milk of lactating cynomolgus monkeys, and IgG is secreted in human milk.
Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts.
The unknown risks to the infant from oral ingestion of rituximab should be weighed against the known benefits of breastfeeding.