Arzerra - instructions for use, dose, side effects, contraindications

Active substanceOfatumoumabOfatumoumab

Similar drugsTo uncover

Arzerra®

concentrate d / infusion

Glaxo United Kingdom Limited United Kingdom

Dosage form: & nbsp

concentrate for solution for infusion.

Composition:

1 ml of the preparation contains:

Active substance
Ofatumoumab	20.0 mg
Excipients
Sodium acetate trihydrate	6.80 mg
Disodium Edetate	0.019 mg
Polysorbate 80	0.20 mg
Arginine	10.00 mg
Sodium chloride	2.98 mg
Hydrochloric acid	q.s. to pH 5.5
Water for injections	q.s. up to 1 ml

Description:

Transparent or opalescent, colorless or pale yellow liquid. After filtering through the attached built-in filter with a pore diameter of 0.2 μm, visible particles should be absent.

Pharmacotherapeutic group:Monoclonal antibodies.

ATX: & nbsp

L.01.X.C.10 Ofatumoumab

Pharmacodynamics:

Mechanism of action

Ophatumumab is a human monoclonal antibody (isotype IgG1), specifically binding to the epitope, which includes both small and large extracellular loops of the molecule CD20. Molecule CD20 is a transmembrane phosphoprotein that is expressed on B lymphocytes, from pre-B cells to mature B lymphocytes, as well as on cells of B-cell tumors. B-cell tumors include chronic lymphocytic leukemia (CLL) (usually accompanied by a lower degree of expression CD20) and non-Hodgkin's lymphomas (in> 90% of tumors expression level CD20 tall).When bound to an antibody, the molecule CD20 remains on the cell membrane, is not removed from its surface (shedding) and does not enter the cell (internalization).

Binding ofatumumab with a specific epitope of the molecule located near the membrane CD20 causes binding and activation of complement on the surface of the cell, which leads to the development of a complement-dependent cytotoxic reaction and lysis of the tumor cell. It was shown that ofatumumab causes a pronounced lysis of the cells, accompanied by a high level of expression of the protective complement proteins. In addition, the binding of ofatumumab causes cell death and the mechanism of antibody-dependent cellular cytotoxicity. It was also shown that ofatumumab causes lysis of cells with both high and low expression CD20, as well as cells resistant to rituximab.

Pharmacodynamic properties

In patients with hematological tumor diseases, the B-cell content in the blood decreased after the first administration of ofatumumab. In patients with CLL, resistant to previous treatment, the mean reduction in B-cell content in the blood after the first administration was 22%, and after the eighth weekly administration, 92%.In most patients, the B-cell content in the blood remained low throughout the course of treatment and remained low for almost 15 months after the last administration of the drug in patients responding to therapy.

In patients with CLL who had not previously received treatment, the median decrease in the number of B lymphocytes after the first cycle and before the start of the sixth monthly cycle was 94% and> 99% for ofatumumab in combination with chlorambucil and 73% and 97% with chlorambucil alone. Six months after the last drug administration, the median decrease in B-lymphocyte count was> 99% for ofatumumab in combination with chlorambucil and 94% for chlorambucil alone.

Immunogenicity

Protein preparations like ofatumumab may elicit an immune response. As part of the CLL clinical study, serum samples from 440 patients were tested for antibodies to ophatumum during and after treatment for 4 to 45 weeks (using enzyme-linked immunosorbent assay or electrochemiluminescence). In patients with CLL, after therapy with ophatumum, no antibodies to ophatumumab were detected.

Pharmacokinetics:

Suction

Ophatumumab is administered by intravenous infusion, so the term "absorption" is not applicable.

The maximum concentrations of ofatumumab in the serum were usually observed at the end of the injection or immediately afterwards. Data on the pharmacokinetics of the drug were obtained for 215 patients with CLL, resistant to previous treatment. The geometric mean for the maximum concentration in the blood plasma (C_mOh) after the first administration (300 mg) was 61 μg / ml, after the eighth weekly administration (the seventh dose of 2000 mg), the geometric mean for C_mOh was 1391 μg / ml, and the geometric mean for the area under the pharmacokinetic curve of the concentration-time relationship (AUQ_(o-∞)) was 463.418 μg-h / ml; after the twelfth administration (the fourth monthly dose of 2000 mg), the geometric mean for C_mOh was 827 μg / ml, and the geometric mean for AUC (about-∞) was 203.536 μg∙h / ml. In patients with CLL who had not previously received therapy, after treatment with ofatumumab and chlorambucil, the average geometric values of C_mOh after the first administration (300 mg), administration of 1000 mg on day 8, and administration of 1000 mg in the fourth monthly cycle were 52 μg / ml, 241 μg / ml and 285 μg / ml, respectively; geometric mean values AUQ_(o_-_∞₎ in the fourth monthly cycle were 65,100 μg∙h / ml.

Distribution

The volume of distribution of ophatumumab is small. The average value of the volume of distribution in the stationary state (ORSS), depending on the dose, the number of administration and in different studies varied from 1.7 liters to 8.1 liters.

Metabolism

Ophatumumab is a protein for which the usual pathway of metabolism is the destruction of proteolytic enzymes to peptides and individual amino acids. Therefore, biotransformation studies of the drug were not conducted.

Excretion

Ophatumumab is excreted from the body in two ways: not related to the target, like all other molecules IgG, and due to interaction with the target, namely binding to B-cells. Even after the first administration of ophatumumab, a rapid and persistent decrease in the number CD20⁺ B cells, so when further administration of the drug, it will be associated with a much smaller amount CD20⁺ cells. As a result, with subsequent administration of ofatumumab, the values of its clearance (CR) will be lower, and the value of the half-life (t₁_/2) is significantly higher than when it was first introduced; with repeated weekly administration of the value AUC and C_mOh increased in

much more than was expected for the expected accumulation of ofatumumab, calculated on the basis of the data obtained at its first administration.

In studies conducted in patients with recurrent or resistant XLL, geometric mean values KL and t_1/2 (range: 4.3-1122 ml / h) and 1.3 days (range: 0.2-6.0 days) after the first administration, 8.5 ml / h (range: 1.3 - 41.5 ml / h) and 11.5 days (range: 2.3-30.6 days) after the fourth administration, 11.7 ml / hr (range: 3.9-54.2 ml / h) and 13.6 days (range: 2.4-36.0 days) after the eighth administration and 12.1 ml / h (range: 3.0-233 ml / h) and 11.5 days (range: 1.8- 36.4 days) after the twelfth administration.

In patients with XLL, previously untreated, after therapy with ofatumumab and chlorambucil, average geometric values KL and t₁_/2 for ofatumumab were 15.4 ml / h (range 4.1-146 ml / h) and 18.5 days (range 2.7-82.6 days) after the fourth administration.

Special patient groups

Patients of advanced age (65 years and older)

As was shown in a cross-sectional population analysis of pharmacokinetics in patients aged 21 to 87 years in different studies, age did not have a significant effect on the pharmacokinetics of ofatumumab.

Children and adolescents (up to 18 years of age)

Data on pharmacokinetics of ofatumumab in this age group are absent.

Floor

In a cross-sectional analysis, it was shown that the floor had a moderate effect (12%) on the central volume of the distribution of ofatumumab - in women C_mOh and AUC were higher (in the analyzed group, 48% of patients were men and 52% were women). These differences were considered to be of no clinical significance, so adjusting the dose according to the patient's sex is not recommended.

Patients with impaired renal function

In a cross-sectional population analysis, patients with creatinine clearance rates ranging from 26 to 287 ml / min showed no significant relationship between the creatinine clearance value determined before the administration of ofatumumab and the pharmacokinetics of the latter. Correct the dose of the drug for patients with mild to moderate renal impairment (creatinine clearance> 30 mL / min) is not recommended. For patients with severe renal impairment (creatinine clearance <30 mL / min), data on the pharmacokinetics of ofatumumab are limited.

Patients with impaired hepatic function

Special studies to study the effect of liver function abnormalities were not carried out. Because the ofatumumab, like all other molecules IgG1, catabolized with proteolytic enzymes, the prevalence of which is not limited to liver tissues, liver function disorders can hardly have any effect on the rate of ofatumumab excretion from the body.

Indications:

Chronic lymphocytic leukemia (XLL) in patients who had not previously received treatment

Ophatumumab is intended for use in combination therapy based on alkylating agents in patients with CLL who have not previously received treatment and who are not eligible for fludarabine therapy.

Recurrent or resistant CLL

Treatment of patients with CLL with ineffectiveness of previous therapy with the inclusion of fludarabine and / or alemtuzumab.

Contraindications:

- Hypersensitivity to ofatumumab or any other component,

included in the preparation;

- children and adolescents under 18;

- severe renal dysfunction (creatinine clearance <30 mL / min);

- pregnancy and the period of breastfeeding.

Carefully:Hepatitis B in history, pulmonary dysfunction and heart disease in the anamnesis.

Pregnancy and lactation:contraindicated

Dosing and Administration:

Ophatumumab should be administered under the supervision of a physician with experience in the use of antitumor drugs. In connection with the potential for the development of anaphylactoid reactions, the administration of ofatumumab should be carried out in the conditions of immediate availability of equipment and medicines needed to provide emergency assistance in such situations.

The drug is administered as an intravenous infusion and must be diluted before use. Concentrated solution should be mixed only with 0.9% solution of sodium chloride for infusions (see subsection "Method of use"). It is not recommended to mix ofatumumab with other drugs in the infusion tanks.

Premedication

In the period from 30 minutes to 2 hours before each administration, patients should receive as a premedication the drugs listed below.

CLL in patients who have not previously received treatment

paracetamol (acetaminophen) orally 1000 mg (or analog), and

antihistamine drug (diphenhydramine 50 mg or cetirizine 10 mg or an analogue), orally or intravenously, and

glucocorticosteroid (prednisolone 50 mg or analog) intravenously.

After the first and second administration, if the patient does not have serious adverse reactions (CHF) associated with the administration, the doctor's decision, in subsequent administrations, it is possible to reduce the dose of glucocorticosteroid for premedication or to cancel its administration.

Recurrent or resistant CLL

- paracetamol (acetaminophen) orally 1000 mg (or analog), and

antihistamine drug (diphenhydramine 50 mg or cetirizine 10 mg or an analogue), orally or intravenously, and

- glucocorticosteroid (prednisolone 100 mg or analog) intravenously.

If the second weekly administration is completed without the development of the CHD associated with the administration, then, according to the doctor's decision, the dose of the glucocorticosteroid may be reduced for injections 3-8.

Before the ninth introduction (the first monthly infusion), patients should receive the preparations for premedication indicated above, in a full dose. After the ninth introduction, in the absence of CHP associated with the administration, the dose of the glucocorticosteroid may be reduced to an equivalent 50 mg of prednisolone, as determined by the physician.

Doses

In patients with CLL who had not previously received treatment

The recommended dose is: 300 mg of ophatumumab for the first administration, then, after 1 week, 1000 mg for the 8th day (cycle 1); further 1000 mg on the 1st day of each subsequent cycle until the best response is achieved or for a maximum of 12 cycles (every 28 days).

First introduction

The initial rate of administration of ofatumumab at the first administration should be 12ml / h. During the infusion, the speed should be increased every 30 minutes to a maximum speed of 400 ml / h (see subsection "Method of use").

Subsequent introduction

If the first administration is completed without the development of the CHP associated with the administration, subsequent administrations can be performed at an initial rate of 25 ml / h, which should be increased every 30 minutes until a maximum rate of 400 ml / h is reached. (see subsection "Method of use ").

Recurrent or resistant CLL

The recommended dose is 300 mg of ofatumumab for the first administration and 2000 mg for all subsequent administrations. The introduction scheme provides for 8 consecutive

weekly injections, and 4-5 weeks later - 4 consecutive monthly (ie every 4 weeks) administration.

First and second introduction

The initial rate of administration of ophatumum at the first and second administration should be 12 ml / h.During the infusion, the speed should be increased every 30 minutes to a maximum speed of 200 ml / h (see subsection "Method of use ").

Subsequent introduction

If the second administration is completed without the development of the CHP associated with the administration, subsequent administrations can be carried out at an initial rate of 25 ml / h, which should be increased every 30 minutes until a maximum rate of 400 ml / h is reached (see subsection "Method of use").

Dose change and resumption of treatment in patients with CLL who had not previously received treatment and in patients with relapsed or resistant CLL

The development of adverse reactions associated with the administration of ofatumumab may necessitate a reduction in the rate of administration.

- In case of development of mild or moderate unwanted reactions, the administration should be stopped and, if the patient's condition remains stable, restart again at a rate equal to half that at which the introduction was interrupted. If, at the time of discontinuation of ophatumumab administration, the rate did not increase from the initial rate of 12 ml / h due to the development of unwanted reactions, then with the resumption of administration, it should be carried out at a standard initial rate of 12 ml / h.Further, the rate of administration, taking into account the patient's tolerance of the drug and at the discretion of the doctor, can be increased according to the standard scheme (so that the speed is doubled no faster than every 30 minutes).

- In the case of CHP development, administration should be discontinued and, if the patient remains stable, resume again at a rate of 12 ml / h. Further, the rate of administration, taking into account the patient's tolerance of the drug and at the discretion of the doctor, can be increased according to the standard scheme (so that the speed is doubled no faster than every 30 minutes).

Method of use

1) Before the cultivation of ophatumumab

Before breeding check ofatumumab concentrate for the presence of particles in it and color changes. The preparation is colorless or pale yellowidkAwn. Do not use ofatumumab if its color is changed. The concentrate may contain a small amount of visible particles. These particles will be removed by the filters included in the insertion kit.

Do not shake vial with the drug before carrying out the described check.

2) How to prepare a solution for infusions

Before administration concentrate ofatumumab must be diluted in 0.9% solution of sodium chloride for infusions in aseptic conditions.

300 mg dose with the use of vials containing 5 ml of the preparation

Use 3 vials (15 ml in total, 5 ml each in a vial):

- from a container with 1000 ml of a 0.9% solution of sodium chloride for infusions, select and dispose of 15 ml of solution;

- from each of the 3 vials with ophatumumab, take 5 ml of concentrate (total 15 ml) and enter them into a container with 985 ml of 0.9% sodium chloride solution for infusion;

- do not shake the container - Mix the contents by cautious overturning.

Dose 1000 mg with the use of vials containing 50 ml of the preparation Use 1 bottle:

- from a container with 1000 ml of 0.9% sodium chloride solution for infusions, select and dispose of 50 ml of the solution;

- take 50_ml of concentrate and enter them into a container with 985 ml of 0.9% sodium chloride solution for infusion;

- do not shake the container - Mix the contents by cautious overturning.

A dose of 2000 mg

A dose of 2000 mg from vials containing

5 ml of the drug

50 ml of the drug

To receive a dose of 2000 mg, use 20 vials (total - 100 ml, 5 ml in a vial):

- from a container with 1000 ml of 0.9% sodium chloride solution for infusions, remove and remove 100 ml of solution;

- from each of the 20 vials with ophatumumab, take 5 ml of concentrate (total-100 ml) and insert them into a container with 900 ml of 0.9% sodium chloride solution for infusion;

- do not shake the container - mix the contents by cautious overturning.

To obtain a dose of 2000 mg, use 2 vials (total - 100 ml, 50 ml in a vial):

- from a container with 1000 ml of 0.9% sodium chloride solution for infusions, remove and remove 100 ml of solution;

- from each of 2 vials with ofatumumab take 50 ml of concentrate (total - 100 ml) and enter them into a container with 900 ml of 0.9% solution of sodium chloride for infusions;

- do not shake the container -

mix the contents by cautious overturning.

3) Introduction

Ophatumumab should not be administered intravenously quickly or bolusily. For

Intravenous administration, the infusion systems with built-in filters attached to the preparation are used.

Concentrate of ofatumumab for the preparation of solution for infusions does not contain preservatives, therefore, its dilution should be carried out under aseptic conditions. The prepared infusion solution must be stored at a temperature of no higher than 25 ° C and used within 24 hours after preparation.After this period, the unused solution should be destroyed.

Ophatumum should not be mixed or administered concomitantly with other drugs or solutions for intravenous administration. To avoid this, before and after the administration of ofatumumab, it is necessary to wash the system for administration with 0.9% sodium chloride solution.

CLL the patients who had not previously received treatment

The first administration is carried out for 4.5 hours (see section "Method of administration and dose") through the infusion system or through a permanent catheter, in accordance with the following scheme.

Infusion Scheme for 1 administration

Time, min	Infusion rate, ml / h
0-30	12
31-60	25
61-90	50
91 - 120	100
121 -150	200
151-180	300
More than 180	400

If the first introduction has passed without the development of the NDS, then the remaining administration (2-13) of 1000 mg should be administered within 4 hours (see section "Method of administration and dose"), through the infusion system or through a permanent catheter, in accordance with the following scheme.

The infusion scheme for the administration of ofatumumab from 2 to 13

Time, min	Infusion rate, ml / h
0-30	25
31-60	50

61-90	100
91 - 120	200
More than 121	400

Recurrent or resistant CLL

The first and second administration of the drug is carried out for 6.5 hours {cm. section "Method of administration and dose") through the infusion system or through a permanent catheter in accordance with the following scheme.

Infusion Scheme for 1 and 2 injections

Time, min	Infusion rate, ml / h
0-30	12
31-60	25
61-90	50
91-120	100
More than 121	200

If the second introduction is without the development of CHP, the remaining administration (3-12) should be performed within 4 hours (see section "Method of administration and dose") through the infusion system or through a permanent catheter in accordance with the following scheme.

The infusion scheme for the administration of ophatumumab from 3 to 12

The infusion scheme for the administration of ofatumumab from 3 to

Time, min	Infusion rate, ml / h
0-30	25
31-60	50
61-90	100
91-120	200
More than 121	400

Special patient groups

Children

The safety and effectiveness of ofatumumab in children younger than 18 years of age have not been investigated.

Elderly patients

There was no significant effect of age on the efficacy and safety of the drug. Given the available data on the effectiveness and safety of the drug in the elderly, dose adjustment in this group is not required.

Patients with impaired renal function

No special studies of ofatumumab in patients with impaired renal function have been performed. Nevertheless, it is unlikely that the dose of the drug will need to be adjusted for patients with impaired renal function.

Patients with impaired hepatic function

No special studies of ofatumumab have been conducted in patients with impaired liver function.However, it is unlikely that patients with a dysfunction of the liver will need to adjust the dose of the drug.

Side effects:

Adverse events recorded with the use of the preparation Arzerra® in the form of monotherapy or in combination with an alkylating agent are presented below and listed in accordance with the damage to organs and organ systems and frequency of occurrence (classification MedDRA). Frequency of occurrence is defined as follows: Often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1 000 and <1/100), rarely (> 1/10 000 and <1/1 000). Frequency categories were formed on the basis of clinical studies of the drug.

Violations of the blood and lymphatic system

Very often: neutropenia, anemia.

Often: febrile neutropenia, thrombocytopenia, leukopenia.

Infrequently: agranulocytosis, coagulopathy, lymphopenia, aplasia of erythrocyte

germ.

Immune system disorders Often: hypersensitivity *.

Infrequently: anaphylactic reactions, including anaphylactic shock *.

Disorders from the metabolism and nutrition Infrequently: a tumor lysis syndrome.

Heart Disease Often: tachycardia *.

Vascular disorders

Often: arterial hypertension *, arterial hypotension *.

Disturbances from the respiratory system, chest and mediastinal organs

Often: pain in the throat-pharyngeal region *, shortness of breath *, cough *, bronchospasm *,

discomfort in the thorax *, nasal congestion *, hypoxia *.

Disorders from the gastrointestinal tract

Very often: nausea.

Often: diarrhea *.

Infrequent: the obstruction of the small intestine.

Disturbances from the skin and subcutaneous tissues Very often: rash *.

Often: itching *, urticaria *, "hot flashes" *.

Disturbances from musculoskeletal and connective tissue Often: back pain.

General disorders and disorders at the site of administration Very often hyperthermia *.

Often: fatigue *, chills *, hyperhidrosis *, cytokine release syndrome *.

Secondary Infections

Very often: bronchitis, pneumonia.

Often: sepsis, septic shock, infection Herpes zoster, infections

urinary tract.

Unknown: progressive multifocal leukoencephalopathy.

* These phenomena are probably associated with the use of ofatumumab, and are infusion reactions that usually occur after the start of the drug administration or within 24 hours after its completion (see section "Special instructions").

Post-registration data

Infections and parasitic diseases

Rarely: hepatitis B (infection or reactivation) (see section "Special instructions").

Overdose:

The results of clinical studies of the preparation Arzerra® do not contain any data on cases of overdose of ophatumumab.

Interaction:

Ophatumumab does not have a clinically significant effect on the pharmacokinetics of chlorambucil or its active metabolite, phenylacetic mustard. When ofatumumab is used together with drugs that have immunosuppressive activity, an increased risk of developing infectious diseases is possible.

Special instructions:

Reactions to administration

With the use of ofatumumab, there may be reactions to the administration requiring temporary discontinuation of treatment or its withdrawal. To weaken the reaction to the administration, premedication can occur, but even in this case the reactions can develop, mainly during the first administration. Reactions to administration may include: anaphylactic reactions, adverse cardiac events, chills, cough, cytokine release syndrome, diarrhea, dyspnea, fatigue, hot flashes, increased or decreased blood pressure, nausea, pain, fever, rash, and urticaria.Cases of CHF development for the administration of ofatumumab, including cytokine release syndrome, have been described even with premedication. In the case of the development of CHR for the introduction should immediately stop the introduction of the drug and conduct symptomatic treatment (recommendations for changing the rate of administration of the drug after the development of reactions to the introduction are given in the section "Method of administration and dose"). Most often, reactions to administration develop on the day of the first administration, and with subsequent administration their severity decreases. In patients with a history of lung function disorder, the risk of complications from the respiratory system due to the development of serious reactions to the administration may be increased, therefore, during the administration of ophatumum, the respiratory function should be carefully monitored. Tumor lysis syndrome

In patients with CLL, ophatumumab may develop tumor lysis syndrome (SLO). Medical measures in the SLO include correction of electrolyte balance, control of kidney function, maintenance of water balance and symptomatic treatment.

Progressive multifocal leukoencephalopathy

In patients with CLL treated with cytotoxic drugs, including ofatumum, progressive multifocal leukoencephalopathy (PMLEP) may occur, including death. The diagnosis of PMOLEP should be excluded in all patients who report a development of neurological symptoms or a change in the nature of the neurologic symptoms that existed earlier. If suspected of PIMEP, treatment with ophatumumab should be discontinued and consult a neurologist.

Vaccination

The safety of vaccination with live attenuated or inactivated vaccines and the ability to form a primary or secondary immune response to them during treatment with ofatumum has not been investigated. Since the quantitative content of B cells decreases, the response to vaccination can be weakened. Before vaccinating patients undergoing treatment with ophatumum, it is necessary to assess the risk-to-vaccination ratio of these patients. Due to the risk of infection, live attenuated vaccines should be avoided during or after treatment with ofatumum until the normalization of B-lymphocyte counts. Infection or reactivation of hepatitis B

Infection or reactivation of the hepatitis B virus (HBV), leading in some cases to the development of fulminant hepatitis, hepatic insufficiency and death, developed in patients receiving medications, including ofatumumab, which are classified as cytolytic antibodies directed against CD20. Cases of the disease have been reported in patients with a positive response to the surface antigen of hepatitis B (HBsAg), as well as in patients with a positive response to antibodies to the nuclear antigen of the hepatitis B virus (anti-HBc), but with a negative reaction to HBsAg. Also, reactivation was noted in patients who had the infection resolved (ie having a negative reaction to HBsAg, positive response to anti-HBc and a positive response to antibodies to the surface antigen of the hepatitis B virus [anti-HBs]).

Reactivation HBV is defined as a sharp increase in replication HBV, which manifests itself in the form of a rapid increase in serum DNA concentration HBV or identify HBsAg in a patient who previously had a negative reaction to HBsAg and positive for anti-HBc. Reactivating replication HBV often accompanied by hepatitis, i.e. an increase in the activity of transaminases and, in severe cases, an increase in bilirubin concentration, liver failure and fatal outcome.

Before starting treatment with ofatumumab, all patients should be examined for infection HBV by defining the content HBsAg and anti-HBc. Specialists with experience in the treatment of hepatitis B should consult patients who have previously been identified with hepatitis B virus infection (a negative reaction to HBsAg, positive reaction to anti-HBc), concerning monitoring of the disease and initiation of antiviral therapy for hepatitis B. Treatment with ofatumumab in patients with signs of current infection (positive reaction to HBsAg) Do not start until HBV-Infected patient will not receive adequate treatment.

In patients with HBV-infection in history should be monitored for clinical and laboratory signs of hepatitis or reactivation HBV in the treatment with ofatumumab and for 6-12 months after the last administration of the drug. On cases of reactivation HBV should be reported within 12 months after completion of therapy. Termination of antiviral therapy HBV should be discussed with specialists with experience in the treatment of hepatitis B.

In case of reactivation HBV During ophatumumab treatment, ofatumumab should be discontinued immediately, as well as any concomitant chemotherapy, and appropriate treatment should begin. At present, there is insufficient data on the safety of the resumption of treatment with ofatumumab in patients who have developed reactivation HBV. The resumption of treatment with ofatumumab in patients with HBV resolved after reactivation, should be discussed with specialists with experience in the treatment of hepatitis B.

Cardiovascular diseases

The condition of patients with heart disease in a history should be carefully observed. If patients develop serious or life-threatening heart rhythm disturbances, treatment with ophatumumab should be discontinued.

Bowel obstruction

In patients treated with anti-CD20 monoclonal antibodies, in particular ofatumumab, sometimes marked the development of intestinal obstruction. Patients with complaints of abdominal pain, especially those developing at the beginning of the course of treatment with ophatumum, should be examined and prescribed appropriate therapy.

Laboratory examination

During treatment with ofatumumab, cytopenia was described, including prolonged neutropenia and neutropenia with a late onset during treatment with ofatumum needed at regular intervals to monitor hemogram, including determining the number of neutrophils; If patients develop cytopenia, the study should be done more often. With the development of cytopenia it is necessary to conduct appropriate therapy.

Effect on the ability to drive transp. cf. and fur:

Studies of the effect of ophatumumab on the ability to drive vehicles or work on automatic equipment have not been conducted. Based on the pharmacology of ofatumumab, there is no reason to suspect an adverse effect of the drug on these activities. When considering the possibility of the patient to perform actions that require an increased concentration of attention and speed of psychomotor reactions, one should take into account his clinical condition and profile of undesirable reactions of ofatumumab.

Form release / dosage:Concentrate for solution for infusion, 20 mg / ml.

Packaging:

A clear glass vial of type 1, containing 5 ml or 50 ml of concentrate, sealed with a bromobutyl rubber stopper,aluminum roll and polypropylene cap type flipp-of.

3 vials containing 5 ml of concentrate, complete with two infusion systems with built-in filters with a pore diameter of 0.2 μm, placed in a package, with instructions for use in a cardboard bundle. 1 bottle containing 50 ml of concentrate, complete with two infusion systems with built-in filters with a pore diameter of 0.2 μm, placed in a bag, with instructions for use in a cardboard bundle.

Storage conditions:

Store in a dark place at a temperature of 2-8 ° C. Do not freeze.

Keep out of the reach of children.

CONDITIONS OF TRANSPORTATION

Transport at a temperature of 2-8 ° C. Do not freeze.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001550

Date of registration:01.03.2012

The owner of the registration certificate:Glaxo United Kingdom LimitedGlaxo United Kingdom Limited United Kingdom

Manufacturer: & nbsp

GLAXO OPERATIONS UK, Limited United Kingdom

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp05.03.2014

Illustrated instructions

Instructions

Arzerra® (Arzerra)