Truxima IV Infusion

Introduction

Truxima IV Infusion 10 mg/ml is a monoclonal antibody used in the treatment of various autoimmune diseases and certain types of cancer, particularly non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL). It targets the CD20 protein found on the surface of B-lymphocytes, leading to the destruction of these cells. It is also used in the management of autoimmune diseases like rheumatoid arthritis and pemphigus vulgaris.

Uses

Truxima IV Infusion 10 mg/ml is primarily used in the treatment of:

Non-Hodgkin lymphoma (NHL)
Chronic lymphocytic leukemia (CLL)
Rheumatoid arthritis (in combination with methotrexate)
Granulomatosis with polyangiitis and microscopic polyangiitis
Pemphigus vulgaris
Other autoimmune disorders involving B-cell dysregulation

Brand Name	Truxima
Type	IV Infusion
Weight	10 mg/ml
Generic	Rituximab
Manufacturer	Celltrion Pharma Inc, Korea
Available in	English বাংলা

Mechanism of Action

Truxima IV Infusion 10 mg/ml specifically binds to the CD20 antigen found on the surface of B-lymphocytes. By targeting CD20, rituximab mediates B-cell lysis through multiple mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and apoptosis. The destruction of B cells helps in treating cancers that involve abnormal B-cell proliferation and autoimmune diseases by reducing the autoimmune response.

How Long Does It Take to Work?

The onset of action of rituximab varies depending on the condition being treated. In cancer treatments such as non-Hodgkin lymphoma, clinical effects may be seen within weeks of treatment initiation. In autoimmune conditions like rheumatoid arthritis, improvements may take several weeks to months, with peak effects often observed after 3 to 4 months.

Absorption

Truxima IV Infusion 10 mg/ml is administered intravenously, and its bioavailability is 100%. After administration, it exhibits a biphasic distribution, first rapidly distributing in the extracellular fluids followed by a slower elimination phase. Peak plasma levels are usually achieved during or immediately after the infusion.

Route of Elimination

Truxima IV Infusion 10 mg/ml is cleared from the body mainly through the reticuloendothelial system via phagocytosis by macrophages. It is not significantly metabolized by the liver or kidneys, and its clearance is dependent on its binding to B cells. As the B-cell count decreases, the drug's clearance rate also decreases.

Dosage

Administration only as an Intravenous Infusion: It should not be administered as an intravenous push or bolus. Rituximab should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur. It should be premedicated before each infusion. Or, as directed by the registered physicians.

First Infusion: Standard Infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.

For Pediatric Patients with mature B-cell NHL/B-AL: Initiate infusion at a rate of 0.5 mg/kg/hr (maximum 50 mg/hr). In the absence of infusion toxicity, increase infusion rate by 0.5 mg/kg/hr every 30 minutes, to a maximum of 400 mg/hr.

Subsequent Infusions: Standard Infusion: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr. For Previously Untreated Follicular NHL and DLBCL adult patients: If patients did not experience a Grade 3 or 4 infusion-related adverse event during Cycle 1, a 90-minute infusion can be administered in Cycle 2 with a glucocorticoid-containing chemotherapy regimen. Initiate at a rate of 20% of the total dose given in the first 30 minutes and the remaining 80% of the total dose given over the next 60 minutes. If the 90-minute infusion is tolerated in Cycle 2, the same rate can be used when administering the remainder of the treatment regimen (through Cycle 6 or 8). Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count greater than or equal to 5,000/mm3 before Cycle 2 should not be administered the 90-minute infusion.

Recommended Dose for Non-Hodgkin’s Lymphoma (NHL): The recommended dose is 375 mg/m 2 as an intravenous infusion according to the following schedules

Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL: It should be administered once weekly for 4 or 8 doses.

Retreatment for Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL: It should be administered once weekly for 4 doses.

Previously Untreated, Follicular, CD20-Positive, B-Cell NHL: It should be administered on Day 1 of each cycle of chemotherapy for up to 8 doses. In patients with complete or partial response, initiate Rituximab maintenance eight weeks following completion of a rituximab product in combination with chemotherapy. It should be administered as a single-agent every 8 weeks for 12 doses.

Non-progressing, Low-Grade, CD20-Positive, B-Cell NHL, after first-line CVP chemotherapy: Following completion of 6-8 cycles of CVP chemotherapy, It should be administered once weekly for 4 doses at 6-month intervals to a maximum of 16 doses.

Diffuse Large B-Cell NHL: It should be administered on Day 1 of each cycle of chemotherapy for up to 8 infusions.

Pediatric patients aged 6 months and older with previously untreated mature B-cell NHL/B-AL: Rituximab is given in combination with systemic Lymphome Malin B (LMB) chemotherapy. In total, six infusions of Rituximab are given, two doses during each of the induction courses, COPDAM1 and COPDAM2, and one dose during each of the two consolidation courses of CYM/CYVE.

Recommended Dose for Chronic Lymphocytic Leukemia (CLL): The recommended dose is 375 mg/m 2 the day prior to the initiation of FC chemotherapy, then 500 mg/m 2 on Day 1 of cycles 2-6 (every 28 days).

Recommended Dose for Rheumatoid Arthritis (RA): Rituximab should be administered as two-1,000 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-related 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.

Recommended Dose for Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA): Rituximab should be administered as a 375 mg/m 2 intravenous infusion once weekly for 4 weeks for patients with active GPA or MPA. Glucocorticoids administered as methylprednisolone 1,000 mg intravenously per day for 1 to 3 days followed by oral prednisone as per clinical practice. This regimen should begin within 14 days prior to or with the initiation of Rituximab and may continue during and after the 4 week induction course of Rituximab treatment.

Recommended Dose for Pemphigus Vulgaris (PV): Rituximab should be administered as two-1,000 mg intravenous infusions separated by 2 weeks in combination with a tapering course of glucocorticoids.

Maintenance treatment: Rituximab should be administered as a 500 mg intravenous infusion at Month 12 and every 6 months thereafter or based on clinical evaluation.

Treatment of relapse: Rituximab should be administered as a 1,000 mg intravenous infusion on relapse, and consider resuming or increasing the glucocorticoid dose based on clinical evaluation. Subsequent infusions of Rituximab may be administered no sooner than 16 weeks following the previous infusion.

The dosage of rituximab depends on the condition being treated:

Non-Hodgkin Lymphoma: Typically 375 mg/m² per infusion, usually given weekly for 4 to 8 weeks, depending on the regimen.
Chronic Lymphocytic Leukemia: 375 mg/m² on the first infusion, followed by 500 mg/m² for subsequent infusions in combination with chemotherapy.
Rheumatoid Arthritis: 1000 mg administered as two infusions separated by two weeks, in combination with methotrexate.
Granulomatosis with Polyangiitis and Microscopic Polyangiitis: 375 mg/m² once weekly for 4 weeks.

Administration

Truxima IV Infusion 10 mg/ml is administered via intravenous infusion. The initial infusion is given slowly to monitor for infusion reactions, with subsequent doses infused at faster rates depending on patient tolerance. Pre-medications such as corticosteroids, acetaminophen, and antihistamines are often given to reduce the risk of infusion reactions.

Side Effects

Common side effects of rituximab include:

Infusion-related reactions (fever, chills, hypotension)
Fatigue
Nausea
Headache
Infections, due to immunosuppression
Cough or throat irritation

Serious side effects include:

Progressive multifocal leukoencephalopathy (PML)
Severe infusion reactions
Tumor lysis syndrome
Severe infections
Hepatitis B reactivation

Toxicity

Toxicity from rituximab can lead to severe infusion reactions, infections, or immune suppression. Overdose is rare but can lead to increased risk of infections and other complications due to excessive B-cell depletion. In case of toxicity, supportive care and discontinuation of treatment are recommended.

Precautions

Truxima IV Infusion 10 mg/ml should be used with caution in patients with a history of hepatitis B or other chronic viral infections, as it can lead to viral reactivation. Caution is also needed in patients with active infections or compromised immune systems. Infusion reactions are common, especially with the first dose, so close monitoring is required.

Interaction

Truxima IV Infusion 10 mg/ml may interact with other immunosuppressive agents, increasing the risk of infections. Live vaccines should be avoided during treatment, and any vaccine administration should be discussed with a healthcare provider. Truxima IV Infusion 10 mg/ml also increases the risk of reactivation of latent viruses such as hepatitis B.

Disease Interaction

Truxima IV Infusion 10 mg/ml is contraindicated in patients with active, severe infections. Patients with a history of hepatitis B infection are at risk of reactivation, and prophylactic antiviral therapy may be required. Truxima IV Infusion 10 mg/ml should also be used cautiously in patients with cardiovascular disease due to the risk of infusion reactions.

Drug Interaction

Truxima IV Infusion 10 mg/ml may interact with other immunosuppressants such as methotrexate or corticosteroids, increasing the risk of infection. Combining rituximab with live vaccines should be avoided. It may also interact with drugs that affect immune function, such as TNF inhibitors.

Food Interactions

There are no significant food interactions with rituximab. Patients are not required to follow any special dietary restrictions while undergoing treatment with rituximab.

Pregnancy Use

Truxima IV Infusion 10 mg/ml is classified as Pregnancy Category C. Animal studies have shown adverse effects on the fetus, but there are limited studies in humans. Truxima IV Infusion 10 mg/ml should be used during pregnancy only if the potential benefits justify the potential risks to the fetus. Women of childbearing age are advised to use effective contraception during and for at least 12 months after treatment.

Lactation Use

It is not known whether rituximab is excreted in human breast milk. Given the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during rituximab treatment and for several months following the final dose.

Acute Overdose

There is limited information on rituximab overdose, but excessive doses may lead to heightened risk of infusion reactions, infections, and immune suppression. Treatment is supportive, and close monitoring of the patient's condition is required. No specific antidote exists for rituximab overdose.

Contraindication

Truxima IV Infusion 10 mg/ml is contraindicated in patients with known hypersensitivity to the drug or any of its components. It should not be used in patients with active, severe infections. Patients with active hepatitis B should avoid rituximab unless under strict antiviral prophylaxis and monitoring.

Use Direction

Truxima IV Infusion 10 mg/ml is given intravenously under the supervision of a healthcare professional. Patients are closely monitored during and after administration for infusion-related reactions. Pre-medications such as antihistamines, acetaminophen, and corticosteroids may be used to reduce the likelihood of adverse reactions.

Storage Conditions

Truxima IV Infusion 10 mg/ml should be stored in a refrigerator at a temperature between 2°C and 8°C (36°F to 46°F). It should not be frozen or shaken, and should be kept in its original packaging to protect it from light. Once diluted for infusion, the solution must be used within a specified time, typically 24 hours, depending on the storage conditions.

Volume of Distribution

Truxima IV Infusion 10 mg/ml has a limited volume of distribution, largely confined to the vascular and interstitial compartments. Its distribution is restricted to extracellular fluids, where it can bind to circulating and tissue-resident B cells.

Half Life

The half-life of rituximab varies depending on the number of circulating B cells. In patients with higher B-cell counts, the half-life is shorter, typically around 76 to 480 hours (approximately 3 to 20 days). In patients with depleted B cells, such as those undergoing repeated doses, the half-life is longer.

Clearance

Truxima IV Infusion 10 mg/ml is cleared primarily through the reticuloendothelial system, where it is degraded by macrophages after binding to CD20-positive B cells. The clearance rate decreases as B cells become depleted, leading to a longer half-life with successive doses.

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