Redditux 10 mg/ml 10 ml

Rituximab is a chimeric mouse/human monoclonal antibody that binds specifically to the transmembrane antigen CD20. This antigen is located on pre-B-lymphocytes and mature B-lymphocytes, but is absent on hematopoietic stem cells, pre-B cells, normal plasma cells, cells of other tissues and is expressed in more than 95% of B-cell non-Hodgkin lymphomas.

CD20 expressed on the cell after binding to the antibody is not internalized and ceases to enter the extracellular space from the cell membrane. CD20 does not circulate in plasma as a free antigen and therefore does not compete for binding to antibodies.

Rituximab binds to the CD20 antigen on B-lymphocytes and initiates immunological reactions mediating B-cell lysis. Possible mechanisms of cell lysis include complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and apoptosis induction. Rituximab increases the sensitivity of human B-cell lymphoma cell lines to the cytotoxic effects of some chemotherapeutic agents in vitro.

B-cell counts in peripheral blood decrease below normal after the first drug administration and begin to recover in patients with hematological malignancies after 6 months, reaching normal values after 9-12 months after completion of therapy.

Antibodies to rituximab were not detected in 67 patients examined during treatment of CD20-positive B-cell non-Hodgkin’s lymphoma with Redditux®.

Pharmacokinetics:

Non-Hodgkin’s Lymphoma

In patients with recurrent B-cell lymphoma, the serum concentration of rituximab and its half-life (T1/2) increase with increasing dose. After the first intravenous infusion of 375 mg/m2, the T1/2 of rituximab was 76.3 h and 205.8 h after the fourth infusion; maximum concentration (Cmax) was 205.6 µg/mL after the first infusion and 464.7 µg/mL after the fourth infusion; plasma clearance was 0.0382 L/h and 0.0092 L/h, respectively. Individual differences in serum concentrations of the drug are quite pronounced.

With effective treatment, serum concentrations of rituximab are significantly higher. Drug concentrations are negatively correlated with tumor burden. Traces of rituximab can be detected in the body for 3-6 months after the last infusion.

In patients with diffuse B-cell lymphoma, serum concentrations of rituximab are comparable to those of patients with non-Hodgkin’s lymphoma of low malignancy or follicular lymphoma receiving the same doses of the drug.

Pharmacokinetics in selected patient groups

Gender. The volume of distribution and clearance of rituximab adjusted for body surface area is slightly greater in males than in females, no adjustment of rituximab dose is required.

Patients with renal and hepatic impairment. There are no pharmacokinetic data in patients with renal and hepatic impairment.

Indications

Active ingredient

Composition

1 ml of the drug contains:

the active ingredient:

rituximab – 10.00 mg;

excipients:

Sodium citrate dihydrate – 7.35 mg,

sodium chloride – 9.00 mg,

Polysorbate 80 – 0.70 mg,

water for injection up to 1.00 ml.

How to take, the dosage

Rules for preparation and storage of infusion solution

The required amount of the drug is taken under aseptic conditions and diluted to the calculated concentration (1-4 mg/ml) in an infusion bottle (bag) with 0.9% sodium chloride solution for injection or 5% dextrose solution (solutions must be sterile and apyrogenic). For stirring carefully turn the bottle (package) to avoid foaming. Before administering, the solution should be inspected to make sure there are no foreign impurities or color changes.

The physician is responsible for the preparation, conditions and storage time of the prepared solution prior to use.

Because Redditux® contains no preservatives, the prepared solution should be used immediately.

The prepared Redditux® infusion solution is stable for 24 h at room temperature (up to 25 °C) or for 48 h at 2 to 8 °C. Redditux® is administered intravenously, by drip through a separate catheter. The drug should not be administered intravenously by trickle or bolus!

The recommended initial infusion rate for the first infusion is 50 mg/h, which may be increased by 50 mg/h every 30 minutes thereafter, up to a maximum rate of 400 mg/h. Subsequent infusions can be started at 100 mg/h and increased by 100 mg/h every 30 minutes to a maximum rate of 400 mg/h.

Interaction

The risk of allergic reactions increases when used with other monoclonal antibodies for diagnostic or therapeutic purposes in patients who have antibodies to mouse proteins or anti-chimeric antibodies.

When administered with cyclophosphamide, doxorubicin, vincristine, prednisolone no increase in the incidence of toxic effects has been noted.

Drugs that depress medullary hematopoiesis increase the risk of myelosuppression.

Redditux® is compatible with polyvinyl chloride or polyethylene infusion systems or bags.

Special Instructions

The drug Redditux® is administered under the close supervision of an oncologist or hematologist, with the necessary conditions for resuscitation.

Infusion reactions

The development of infusion reactions may be due to the release of cytokines and/or other mediators. Severe infusion reactions are difficult to distinguish from hypersensitivity reactions or cytokine release syndrome. There have been reports of fatal infusion reactions described during the post-registration use of rituximab. Most patients experience fever with chills or shivering within 30 minutes to 2h after the start of the first rituximab infusion.

Serious reactions include pulmonary symptoms, decreased or increased blood pressure, urticaria, angioedema, nausea, vomiting, weakness, headache, itching, tongue irritation or pharyngeal edema (swelling), rhinitis, hot flashes, pain in the foci and, in some cases, signs of rapid tumor lysis syndrome. Infusion reactions disappear after interruption of rituximab administration and drug therapy (intravenous administration of 0.9% sodium chloride solution, diphenhydramine and acetaminophen, bronchodilators, glucocorticosteroids, etc.).

In most cases, once symptoms have completely disappeared, the infusion can be resumed at a rate that is 50% of the previous rate (e.g., 50 mg/h instead of 100 mg/h). In most patients with non-life-threatening infusion reactions, treatment with rituximab has been completed. Continuation of therapy after complete disappearance of symptoms is rarely accompanied by a recurrence of severe infusion reactions.

30-60 minutes before each infusion it is recommended to perform premedication (analgesics and antihistamines). The prepared solution for infusion should not be administered by jetting.

Pulmonary side effects

Possible increase in symptoms over time or clinical deterioration after initial improvement. Patients with pulmonary symptoms or other severe infusion reactions should be closely monitored until symptoms have resolved. Acute respiratory failure may be accompanied by formation of interstitial lung infiltrates or pulmonary edema, often manifested within the first 1-2 h after the start of the first infusion. If severe pulmonary reactions develop, rituximab infusion should be stopped immediately and intensive symptomatic therapy should be administered. Because initial improvement in clinical symptoms may be followed by worsening, patients should be closely monitored until pulmonary symptoms resolve.

Rituximab mediates the rapid lysis of benign or malignant CD20-positive cells. Tumor lysis syndrome is possible after the first infusion of rituximab in patients with a high number of circulating malignant lymphocytes. Tumor lysis syndrome includes: hyperuricemia, hyperkalemia, hypocalcemia, hyperphosphatemia, acute renal failure, increased LDH activity. Patients at risk (patients with a high tumor burden or a high number of circulating malignant cells (> 25 x 109/l), such as those with chronic lympholeukemia or mantle cell lymphoma) require close medical monitoring and regular laboratory examination. If symptoms of rapid tumor lysis develop, appropriate therapy is given.

In a limited number of cases, rituximab therapy is continued in combination with prophylaxis for rapid lysis syndrome after complete resolution of symptoms. For patients with large numbers of circulating malignant cells (> 25 x 109/L) or high tumor burden (e.g., chronic lympholeukemia or mantle cell lymphoma) in whom the risk of extremely severe infusion reactions may be particularly high, Redditux® should be administered with extreme caution, under close monitoring. The first infusion of the drug should be given at a lower rate in such patients or the dose of Redditux® should be divided over two days during the first cycle of therapy and every subsequent cycle thereafter if the circulating malignant cell count remains >25 x 109/L.

Cardiovascular side effects

Watchful monitoring of patients with a history of cardiovascular disease during infusion is required due to the possibility of low blood pressure, angina pectoris or arrhythmias (atrial flutter and fibrillation). Because of the possibility of development of hypotension at least 12 h before infusion of Redditux® , antihypertensive drugs should be cancelled.

Contraindications

Side effects

Overdose

Pregnancy use