The solution for the sc administration is transparent or opalescent, colorless or yellowish in color.
1 ml
rituximab 120 mg
Auxiliary substances: recombinant human hyaluronidase (rHuPH20) - 2000 ED, L-histidine - 0.53 mg, L-histidine hydrochloride monohydrate - 3.46 mg,?, - trehalose dihydrate - 79.22 mg, L-methionine - 1.49 mg, polysorbate 80 - 0.6 mg, water q / u - up to 1 ml.
11.7 ml - bottles of colorless glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Antitumor and immunomodulating agent. Rituximab is a chimeric mouse / human monoclonal antibody that specifically binds to the transmembrane CD20 antigen.This antigen is located on pre-B lymphocytes and mature B lymphocytes, but is absent on stem hemopoietic cells, pro-B cells, normal plasma cells, cells of other tissues and is expressed in more than 95% of cases with B-cell non-Hodgkin's lymphomas. The CD20 expressed on the cell after binding to the antibody is not internalized and ceases to flow from the cell membrane to the extracellular space. CD20 does not circulate in the plasma as a free antigen, and therefore does not compete for binding to the antibody.
Rituximab binds to the CD20 antigen on B lymphocytes and initiates immunological reactions mediating lysis of B cells. Possible mechanisms of cell lysis include complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis. Rituximab increases the sensitivity of human B-cell lymphoma lines to the cytotoxic effect of certain chemotherapeutic drugs in vitro.
The number of B cells in the peripheral blood after the first administration of the drug is lower than normal and begins to recover in patients with hematologic malignancies after 6 months, reaching normal values ​​12 months after completion of therapy, however, in some cases, the duration of the recovery period of the number of B cells can be more.
Antimony antibodies in the examined patients were not identified. The data obtained show that after the administration of the drug MabThera in the drug form, the solution for the s.c. administration of antibodies to rituximab (anti-chimeric antibodies) is comparable with the MabThera preparation in the form of a drug for the preparation of a solution for infusions .
With the introduction of the drug MabThera in the form of a drug for administration to patients with non-Hodgkin's lymphoma, the incidence of the formation / increase of antibodies to rituximab as a result of therapy was low and similar to that with intravenous administration (2% vs. 1%, respectively) . The frequency of formation / increase of antibodies to recombinant human hyaluronidase (rHuPH 20) with the administration of the drug MabThera in the drug form of the solution for SC administration to patients with non-Hodgkin's lymphoma was 9% compared to 6% with IV introduction. Neither of these patients showed neutralizing antibodies.The total proportion of patients with antibodies to rHuPH20 as a whole did not change during the follow-up period.
The clinical significance of the formation of antibodies to rituximab or antibodies to rHuPH20 after treatment with MabThera in the drug form is not known for the s.c. injection.
The presence of antibodies to rituximab or antibodies to rHuPH20 did not affect the safety or effectiveness of the drug in the study.
PHARMACOKINETICS
Data on pharmacokinetics in patients with non-Hodgkin's lymphoma are given.
Suction
In patients with follicular lymphoma who responded to induction therapy with MabThera in an IV preparation, during maintenance treatment that included at least one MabThera treatment cycle in the I / O form, the median C max rituximab in the blood serum with the subsequent use of MabThera in the dosage form for the SC administration at a fixed dose of 1400 mg every 2 months was 201 Ојg / ml, with the introduction of 189 Ојg / ml every 3 months. Median T max - 3 days.
In previously untreated patients with follicular lymphoma during the 7 cycle of induction therapy, which included one cycle of the MabThera preparation in the IV administration form with the further use of the MabThera preparation in a dosage form for administration at a fixed dose of 1400 mg every 3 weeks in combination with chemotherapy, the geometric mean C max is 236.82 Ојg / ml (coefficient of variation 29.41%).
According to the population-based pharmacokinetic analysis, absolute bioavailability after injection of MabThera in the drug form of the solution for SC administration is 71%.
Distribution
In patients with follicular lymphoma who responded to induction therapy with MabThera in an intravenous drug form during the 2 cycle of maintenance treatment, which included at least one MabThera treatment cycle in an IV preparation, the median the geometric values ​​of the minimum concentration (C trough ) of rituximab in the blood serum with further use of the MabThera preparation in the dosage form for infusion at a fixed dose of 1400 mg once every 2 months and once every 3 months amounted to 32.2 and 12.1 μg / ml, respectively. The average geometric values ​​of AUC within the dosing interval t (AUC t ) were 5430 and 5320 μg / day. In previously untreated patients with follicular lymphoma using MabThera in a dosage form for administration at a fixed dose of 1400 mg every 3 weeks in combination with chemotherapy to the 8 cycle of induction therapy that included one MabThera cycle for IV administration, the geometric mean C trough was 134.6 μg / ml, the AUC t was 3778 μg / day.
Excretion
The median of the final T 1/2 is 29.7 days. With an increase in body surface area, the parameters characterizing the clearance and V d increase. Antibodies to the drug have no clinically significant effect on clearance.
Pharmacokinetics in special clinical cases
With age, the central V d increases and the rate of absorption decreases (in patients older than 60 years), with age not affecting the exposure of rituximab.
Pharmacokinetic data in patients with renal and hepatic insufficiency are absent.
INDICATIONS
Non-Hodgkin's Lymphoma:
- recurrent or chemically resistant B-cell, CD20-positive non-Hodgkin's lymphoma of low grade or follicular;
- follicular lymphoma of III-IV stage - in combination with chemotherapy in previously untreated patients;
- follicular lymphoma - as maintenance therapy after responding to induction therapy;
- CD20-positive diffuse B-large-cell non-Hodgkin's lymphoma - in combination with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone).
DOSING MODE
Before using MabThera В® , you should carefully read the instructions and make sure that the dosage form of the drug (concentrate for the preparation of the infusion solution or solution for the SC administration) and the dosage are appropriate for the patient.
MabTheraВ® solution for administration of 1400 mg is intended only for therapy of non-Hodgkin's lymphoma.
MabThera В® is always administered only if there are necessary conditions for carrying out resuscitation measures under the careful supervision of an oncologist or hematologist.
MabThera drug in the drug form solution for SC administration is not intended for intravenous administration.
The needle for the SC administration should be attached to the syringe immediately before the administration of the drug to prevent possible blockage of the needle .
MabThera preparation in the drug form solution for SC administration should be administered SC only in the anterior abdominal wall. Data on the experience of drug administration in any other zones are absent. Do not enter the drug into the hematoma, places with seals, hypersensitivity, redness, birthmarks, scar tissue.
The drug MabThera in the drug form solution for SC administration and other drugs, also intended for SC administration, should, if possible, be administered at different locations. If the injection is interrupted, it can be resumed in the same place or, if necessary, changed the injection site.
Rules for storing the solution for the s / s injection after fetching into the syringe
After the solution is taken into the syringe, MabTheraВ® solution for IV administration 1400 mg / 11.7 ml is physically and chemically stable for 48 hours at a temperature of 2 В° to 8 В° C or 8 hours at 30 В° C and daylight scattered light. For reasons of microbiological safety, the drug should be used immediately. If the drug is not used immediately, the time and storage conditions of the drug are the responsibility of the user and should not exceed 48 hours at a temperature of 2 В° to 8 В° C or 8 hours at 30 В° C and daylight scattered light - provided that the solution was prepared in controlled and validated aseptic conditions.
Standard dosing regimen
Non-Hodgkin's lymphoma of low grade or follicular
Before each use of MabThera В® it is necessary to perform premedication (analgesic / antipyretics, for example, paracetamol, antihistamine, eg diphenhydramine). If MabThera is not used in combination with chemotherapy containing glucocorticosteroids, then SCS is also part of the premedication.
The first dose of MabTheraВ® should be given to all patients by means of intravenous infusion of the drug in the dosage form with a concentrate for the preparation of a solution for infusions. MabThera drug in the drug form solution for SC administration should be used only in the second and / or subsequent cycles of therapy.
First intravenous administration
The first dose of MabTheraВ® (375 mg / m 2 ) should be given to the patients in the form of an IV infusion of the drug in the form of a drug for the preparation of a solution for infusion. For intravenous administration, use the MabThera preparation in the dosage form of a concentrate for the preparation of a solution for infusion (see the appropriate instructions for medical use).
The recommended initial speed of the first infusion is 50 mg / h, then it can be increased by 50 mg / h every 30 minutes, bringing to a maximum speed of 400 mg / h.
Subsequent w / o introduction
Patients who failed to receive the full dose of the MabThera preparation in the form of a concentrate for the preparation of a solution for infusion should continue to receive MabThera in a drug form for IV administration in subsequent cycles. For more information, see "Special instructions".
Patients who received a full dose of the MabThera preparation in a dosage form concentrate for the preparation of a solution for infusion, in the following cycles, MabThera preparation can be prepared in a dosage form intended for administration.
The injections of the MabThera preparation in the drug form for the SC administration are carried out for approximately 5 minutes.
Initial therapy:
in combination with chemotherapy: 1 cycle MabThera preparation IV at a dose of 375 mg / m 2 , then MabThera preparation at a fixed dose of 1400 mg regardless of body surface area, on the first day of the chemotherapy cycle after intravenous administration of GCS as a component of therapy, during:
- 1 cycle MabThera preparation IV in combination with CVP (cyclophosphamide, vincristine, prednisolone) + 7 cycles MabThera preparation in combination with CVP (cycle: 21 days);
- 1 cycle MabThera IV in combination with MCP (mitoxantrone, chlorambucil, prednisolone) + 7 cycles MabThera preparation in combination with MCP (cycle: 28 days);
- 1 cycle MabThera preparation IV / in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) + 7 cycles MabThera preparation in combination with CHOP (cycle: 21 days); in case of achieving complete remission after 4 cycles, it is possible to limit to 6 cycles (1 cycle MabThera В® IV, then 5 cycles MabThera В® p / k);
- 1 cycle MabThera preparation IV / in combination with CHVP-Interferon (cyclophosphamide, doxorubicin, teniposide, prednisolone + interferon) + 5 cycles MabThera preparation in combination with CHVP-Interferon (cycle: 21 days).
Supportive therapy (after responding to induction therapy):
- in previously untreated patients: MabThera В® at a fixed dose of 1400 mg regardless of body surface area 1 time in 2 months, not more than 2 years (12 injections). If signs of disease progression appear, MabThera should be discontinued;
- with relapsing or chemically resistant lymphoma: MabThera preparation at a fixed dose of 1400 mg irrespective of body surface area once in 3 months, not more than 2 years. If signs of disease progression appear, MabThera should be discontinued.
Correction of dose during therapy
It is not recommended to reduce the dose of MabThera В® .
If MabThera is used in combination with chemotherapy, standard dose reduction regimens for chemotherapeutic drugs
Diffuse B-Large-Cell Non-Hodgkin's Lymphoma
Before each use of MabThera В® it is necessary to perform premedication (analgesic / antipyretics, for example, paracetamol, antihistamine, eg diphenhydramine). If MabThera is not used in combination with chemotherapy containing glucocorticosteroids, then SCS is also part of the premedication.
The first dose of MabTheraВ® all patients should be prepared by iv administration of the drug in a dosage form with a concentrate to prepare a solution for infusion. MabThera drug in the drug form solution for SC administration should be used only in the second and / or subsequent cycles of therapy.
First intravenous administration
The first dose of MabTheraВ® (375 mg / m 2 ) should be given to the patients in the form of an IV infusion of the drug in the form of a drug for the preparation of a solution for infusion. For intravenous administration, MabThera should be used in the form of a drug concentrate for the preparation of a solution for infusions (see the appropriate instructions for medical use).
The recommended initial speed of the first infusion is 50 mg / h, then it can be increased by 50 mg / h every 30 minutes, bringing to a maximum speed of 400 mg / h.
Subsequent w / o introduction
Patients who failed to receive the full dose of the MabThera preparation in the form of a concentrate for the preparation of a solution for infusion should continue to receive MabThera in a drug form for IV administration in subsequent cycles . For more information, see "Special instructions".
Patients who received a full dose of the MabThera preparation in a dosage form concentrate for the preparation of a solution for infusions may receive MabThera in a drug form intended for administration in subsequent cycles.
In combination with chemotherapy according to the CHOP:
1 cycle MabThera preparation IV at a dose of 375 mg / m 2 in combination with CHOP + 7 cycles MabThera preparation at a dose of 1400 mg, regardless of body surface area, in combination with CHOP; on the first day of each cycle of chemotherapy after intravenous administration of GCS as a component of therapy.
Correction of dose during therapy
It is not recommended to reduce the dose of MabThera В® .
If MabThera is used in combination with chemotherapy, standard dose reduction schemes for chemotherapeutic drugs are used.
Special patient groups
In patients older than 65 years, dose adjustment is not required.
SIDE EFFECT
Determination of the frequency of adverse reactions: very often (? 10%), often (? 1% - <10%), infrequently (? 0.1% - <1%).
Experience in the use of the drug in oncohematological diseases
The safety profile of the MabThera preparation in the drug form of the administration solution is comparable with the safety profile of the MabThera preparation in the form of a concentrate for the preparation of a solution for infusions. With SC administration, local skin reactions, including reactions at the site of administration, were very common (in 20% of patients with non-Hodgkin's lymphoma and in 42% of patients with chronic lymphocytic leukemia). Most often local skin reactions in patients with non-Hodgkin's lymphoma included erythema (13%), pain (7%), puffiness (4%), and in patients with chronic lymphatic leukemia - erythema (26%), pain (16%), swelling (5%). In most cases, the events were of mild or moderate severity, except for one patient with non-Hodgkin's lymphoma and two patients with chronic lymphocytic leukemia who had local reactions from the skin of the third degree of severity (rash and erythema, pain, swelling, respectively). Local reactions from the skin of any severity with the introduction of the drug MabThera in the drug form solution for SC administration most often occurred with the first administration of the drug SC (cycle 2), then at the second injection, the incidence was reduced with subsequent injections.
Anaphylaxis and severe hypersensitivity reactions or cytokine release syndrome, tumor lysis syndrome with the use of the drug Mabthera В® in the dosage form solution for s / c administration in clinical trials was not observed.
The reactions observed at / in the introduction of the drug Mabthera В® in the dosage form of the concentrate for solution for infusion
Mabthera В® in the treatment of non-Hodgkin's lymphoma, low-grade or follicular - monotherapy / maintenance therapy
Reported adverse drug reactions received within 12 months after monotherapy and up to 1 months after maintenance therapy MabThera В® .
Infectious and parasitic diseases: very often - bacterial and viral infections; often - respiratory tract infection *, pneumonia *, sepsis, herpes zoster *, infection accompanied by fever *, fungal infections, infections of unknown aetiology.
From hemopoiesis system: very often - leukopenia, neutropenia; often - thrombocytopenia, anemia; infrequently - lymphadenopathy, blood clotting, transient partial aplastic anemia, hemolytic anemia.
The respiratory system: often - rhinitis, bronchospasm, coughing, respiratory problems, shortness of breath, chest pain; infrequently - hypoxia, impaired lung function, obliterative bronchiolitis, asthma.
Immune system:very often - angioedema; often - a hypersensitivity reaction.
On the part of metabolism and nutrition: frequent - hyperglycemia, weight loss, peripheral edema, facial edema, increased LDH, hypocalcaemia.
From the digestive system: very often - nausea; often - vomiting, diarrhea, indigestion, anorexia, dysphagia, stomatitis, constipation, abdominal pain, sore throat; Infrequent - abdominal enlargement.
Cardio-vascular system:often - a decrease in blood pressure, increased blood pressure, orthostatic hypotension, tachycardia, arrhythmia, atrial fibrillation *, myocardial infarction *, cardiac pathology *; infrequently - left ventricular heart failure *, ventricular and supraventricular tachycardia *, bradycardia, myocardial ischemia * * angina.
From the nervous system: often - dizziness, paresthesia, hypoesthesia, insomnia, anxiety, agitation, vasodilatation; infrequently - dysgeusia.
On the part of the psyche: rarely - nervousness, depression.
On the part of the musculoskeletal system: often - myalgia, arthralgia, muscle hypertonicity, back pain, pain in the neck.
Skin and subcutaneous tissue disorders:very often - itching, rash; often - urticaria, sweating night, sweating, alopecia *.
From a sight organ: often - disorders lacrimation, conjunctivitis.
On the part of the organ of hearing and balance: often - pain and tinnitus.
From the laboratory parameters: often - reduction in the concentration of immunoglobulin G (IgG).
General disorders and reactions at the injection site: very often - headache, fever, chills, fatigue; often - pain in the foci of the tumor, flu-like symptoms, flushing, weakness; rarely - pain at the injection site.
* rate is valid only for adverse reactions? 3 degrees of severity according to the criteria of the National Cancer Institute Common Toxicity (NCI-CTC).
MabThera В®in combination with chemotherapy (CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), CVP (cyclophosphamide, vincristine, prednisone)) for non-Hodgkin's lymphoma and chronic lymphocytic leukemia (FC (fludarabine, cyclophosphamide)
severe adverse reactions following are additional to those observed with monotherapy / maintenance therapy and / or occurring at a higher frequency.
Infectious and parasitic diseases: very often - bronchitis often - acute bronchitis, sinusitis, hepatitis B * (HBV reactivation and primary infection).
From hemopoiesis system: very often - neutropenia **, febrile neutropenia, thrombocytopenia, and often - pancytopenia, granulocytopenia.
Skin and subcutaneous tissue disorders:very often - alopecia; often - skin diseases.
General reactions: often - fatigue, chills.
* contains frequency based on observations in the treatment of recurrent / chronic lymphocytic leukemia himioustoychivogo scheme R-FC (rituximab, fludarabine, cyclophosphamide).
** prolonged and / or delayed by neutropenia was observed after R-FC circuit completion of therapy in previously untreated patients or in patients with recurrent / chronic lymphocytic leukemia himioustoychivym.
Below are undesirable phenomena encountered during therapy with Mabthera В®with the same frequency (or less) as compared with the control group: hematotoxicity, neutropenic infection, urinary tract infection, septic shock, superinfection lung, implant infection, staphylococcal septicemia, mucous nasal, pulmonary edema, heart failure, sensory disturbances, venous thrombosis , including deep vein thrombosis limbs, mucositis, edema of lower extremities, decreased left ventricular ejection fraction, increased body temperature, general health deterioration, drop, multiple organ failure, bacteremia, decompensation of diabetes.
The safety profile of the drug Mabthera В® in combination with chemotherapy regimens MCP, CHVP-IFN is not different from that in the drug combination with CVP, CHOP or FC in relevant populations.
Responses associated with administration of the drug
monotherapy Mabthera В® (for 4 weeks),
more than 50% of patients were observed phenomenon resembling infusion reactions, most often - at the first infusion. Infusion reactions include chills, shaking, weakness, shortness of breath, nausea, rash, "tides", lowering blood pressure, fever, itching, hives, feeling tongue irritation or swelling of the throat (angioneurotic edema), rhinitis, vomiting, pain in the foci of the tumor, headache , bronchospasm. It reported on the development of symptoms of tumor lysis syndrome.
MabThera В®in combination with chemotherapy for the following schemes: R-CVP (rituximab, cyclophosphamide, vincristine, prednisone) for non-Hodgkin's lymphoma; R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with diffuse large non-Hodgkin's lymphoma
Infusion reactions 3 and 4 severity during infusion or within 24 hours after infusion MabThera В® were noted during the first cycle of chemotherapy in 12% patients. The frequency of infusion reactions decreased with each subsequent cycle and the 8th cycle frequency chemotherapy infusion reactions was less than 1%. Infusion reactions, in addition to the above (with monotherapy Mabthera В®) Include: dyspepsia, rash, increased blood pressure, tachycardia, features of tumor lysis syndrome, in some cases - myocardial infarction, atrial fibrillation, pulmonary edema and acute reversible thrombocytopenia.
Dosage form solution for s / c administration
risk of acute reactions associated with the administration of the drug using a formulation for n / k administration was evaluated in three clinical trials.
In one study in patients with non-Hodgkin's lymphoma, severe reactions associated with the administration of the drug is not registered.
In another study in patients with non-Hodgkin's lymphoma severe reactions associated with administration of the drug (? 3rd severity), it was reported in two patients (2%) after s / c injection and included rash in the site of injection and dry mouth 3 th degree.
In a study of patients with chronic lymphocytic leukemia severe reactions associated with administration of the drug (? 3rd severity) were reported in four patients (5%) after the s / c injection (thrombocytopenia 4th severity and anxiety, erythema injection site and urticaria 3rd severity).
Infections
monotherapy Mabthera В® (within 4 weeks)
Mabthera В®pool causes depletion of B cells in 70-80% of patients and reducing the concentration of immunoglobulins in serum of a small number of patients. Bacterial, viral, fungal infections, and infections unspecified etiology (all, regardless of the cause) developed 30.3% of patients. Severe infection (grade 3 and 4 severe), including sepsis, marked in 3.9% of patients.
Supportive therapy (non-Hodgkin's lymphoma) to 2 years
When therapy with MabThera В®We observed an increase in the overall frequency of infections, including Grade 3-4 infections. No increase in the incidence of infectious complications in maintenance therapy lasting 2 years. Cases of progressive multifocal leukoencephalopathy (PML) with a fatal outcome in patients with non-Hodgkin's lymphoma after disease progression and retreatment.
Mabthera В® in combination with chemotherapy for the following schemes: R-CVP with non-Hodgkin's lymphoma; R-CHOP with diffuse large non-Hodgkin's lymphoma
When therapy with Mabthera В®scheme R-CVP was no increase in the frequency of infections or infestations. The most common were upper respiratory infection (12.3% in the group R-CVP). Serious infections occurred in 4.3% of patients receiving chemotherapy scheme R-CVP; life-threatening infections are not logged in. The proportion of patients with infections of 2-4 severity and / or febrile neutropenia in the R-CHOP group was 55.4%. The total rate of infection of 2-4 severity in R-CHOP group was 45.5%. The frequency of fungal infections severity 2-4 in R-CHOP group was higher than in the CHOP group, due to the higher frequencies of the local candidosis and amounted 4.5%. Frequency of HSV infection 2-4 severity was higher in the group R-CHOP versus CHOP and the group was 4.5%.
From the hematopoietic system
Monotherapy drug Mabthera В® (within 4 weeks)
Severe thrombocytopenia (3 and 4 severity) was observed in 1.7% of patients, severe neutropenia - in 4.2% of patients, severe severity of anemia (3 and 4 severity) - in 1.1% of patients.
Supportive therapy (non-Hodgkin lymphoma) aged 2
Leukopenia (3 and 4 severity) was observed in 5% of patients, neutropenia (grade 3 and 4 severe) - 10% of patients receiving the drug Mabthera В® . The incidence of thrombocytopenia (Grade 3-4) during therapy with Mabthera В® was low and was <1%.
Approximately 50% of patients for whom data were available for recovery of B cells after the induction therapy with Mabthera В® took 12 months or more for recovery of B cells to normal levels.
Mabthera В® in combination with chemotherapy for the following schemes: R-CVP with non-Hodgkin's lymphoma; R-CHOP with diffuse large non-Hodgkin's lymphoma
Severe neutropenia and leukopenia (3 and 4 severity) in patients receiving the drug Mabthera В®in combination with chemotherapy, leukopenia 3 and 4 severity was observed more frequently than patients receiving chemotherapy alone. The frequency of severe leucopenia was 88% in patients treated with R-CHOP. The frequency of severe neutropenia was 24% in the R-CVP, 97% in the R-CHOP. The higher incidence of neutropenia in patients treated with the drug Mabthera В® and chemotherapy was not associated with an increased frequency of infections and infestations when compared to patients receiving chemotherapy alone.
Severe anemia and thrombocytopenia (grade 3 and 4 severe): a significant difference in the incidence of anemia and thrombocytopenia 3 and 4 in the severity was groups.
Cardio-vascular system
Monotherapy MabThera В®(4 weeks),
side effects of the cardiovascular system were noted in 18.8%. The most frequent rise and fall in blood pressure. In rare cases of cardiac arrhythmias observed 3 and 4 severity (including ventricular and supraventricular tachycardia) and angina.
Supportive therapy (non-Hodgkin lymphoma) aged 2
Frequency cardiovascular disorders 3 and 4 severity was similar in patients treated with the drug Mabthera В® and not receiving it. Severe cardiovascular disorders occur in less than 1% of patients not receiving MabThera В® , and 3% of patients receiving the drug (atrial fibrillation at 1%, myocardial infarction, 1%, left ventricular failure at <1%, myocardial ischemia in < 1%).
Mabthera В® in combination with chemotherapy for the following schemes: R-CVP with non-Hodgkin's lymphoma; R-CHOP with diffuse large non-Hodgkin's lymphoma
incidence of cardiac arrhythmias 3 and 4 severity mainly supraventricular arrhythmia (tachycardia, atrial flutter and atrial fibrillation), the group R-CHOP was higher than CHOP group and was 6.9% . All arrhythmias developed or in connection with the infusion of MabThera В®Or were associated with predisposing conditions such as fever, infection, acute myocardial infarction or accompanying diseases of the respiratory and cardiovascular systems. R-CHOP and CHOP group did not differ between a frequency other cardiac adverse events 3 and 4 severity, including heart failure, myocardial disease and coronary artery disease manifestation.
Nervous system
Mabthera В® in combination with chemotherapy for the following schemes: R-CVP with non-Hodgkin's lymphoma; R-CHOP with diffuse large non-Hodgkin's lymphoma
The patients (2%) of R-CHOP group with cardiovascular risk factors developed thromboembolic disorders of cerebral circulation during the first cycle of therapy, in contrast to patients of CHOP groups in which cerebrovascular evolved during the observation period without treatment. The difference between the groups in the incidence of other thromboembolic events was absent.
IgG Concentration
Supportive therapy (non-Hodgkin lymphoma) to 2 years
After induction therapy IgG concentration was below the lower limit of normal (<7 g / L) in the group receiving the drug Mabthera В® , and in the group not receiving the drug. In the group receiving no drug Mabthera В®Median concentration of IgG sequentially increased and exceeded the lower limit of normal, while the median IgG concentration did not change in group receiving drug Mabthera В® . In 60% of patients receiving the drug Mabthera В® for 2 years, IgG concentration remained below the lower limit. The group without drug treatment Mabthera В® in 2 years IgG concentration remained below the lower limit at 36% of patients.
Specific categories of patients
Monotherapy MabThera В® (for 4 weeks)
Older age (65 years?): The frequency and severity of adverse events and adverse events grade 3 and 4 severity did not differ from that in younger patients.
Combination therapy of
high tumor burden (diameter single foci of more than 10 cm) increased frequency of adverse reactions 3 and 4 degrees.
Repeated therapy: frequency and severity of adverse reactions did not differ from those during initial therapy.
Post-registration application MabThera В® in the dosage form of the concentrate for solution for infusion with non-Hodgkin's lymphoma and chronic lymphocytic leukemia
From the cardiovascular system:severe cardiovascular effects associated with infusion reactions such as heart failure and myocardial infarction, mainly in patients with cardiovascular disease history and / or receiving cytotoxic chemotherapy; very rarely - vasculitis predominantly cutaneous (leukocytoclastic).
The respiratory system: respiratory insufficiency and pulmonary infiltrates caused infusion reactions; in addition to adverse events from the lungs, due to infusion reactions observed interstitial lung disease, in some cases fatal.
From hemopoiesis system: reversible acute thrombus
The information is provided for your information, do not self-medicate, it is dangerous for your health.
