Ofatumoumab (Ofatumumabum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Antineoplastic agents - monoclonal antibodies

Included in the formulation
  • Arzerra®
    concentrate d / infusion 
    Glaxo United Kingdom Limited     United Kingdom
    • АТХ:

    L.01.X.C.10   Ofatumoumab

    Pharmacodynamics:

    The drug is a human monoclonal antibody (isotype of IgG1), and specifically binds to the epitope of the molecule Cd20. CD20 molecule is a transmembrane phosphoprotein that is expressed on B lymphocytes, starting from pre-B cells to mature B-lymphocytes as well as on the cells of B-cell tumors. B-cell tumors include chronic lymphocytic leukemia (usually accompanied by lower degree of CD20 expression) and non-Hodgkin's lymphoma (in> 90% of the tumors CD20 high expression level). Upon binding to the antibody molecule CD20 on the cell membrane is not removed from the surface (shedding) and does not flow into the cell (internalization).

    Binding ofatumumab with membranes positioned near a specific epitope of CD20 molecules cause binding and complement activation on the cell surface, which leads to the development of complement cytotoxic reactions and lysis of the tumor cells. 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 of CD20, as well as cells resistant to rituximab.

    Pharmacokinetics:

    Cmax Ophatumumab in serum was usually observed at the end of the injection or immediately afterwards. Vd okatumumab is small. Average value Vd In the stationary state, depending on the dose, it varied from 1.7 to 5.1 liters. Metabolized as other proteins entering the body, splitting with proteolytic enzymes. Ofatumoumab is removed from the body in two ways: not related to the target, like all other IgG molecules, and due to interaction with the target, namely, binding to B cells. Even after the first administration of ofatumumab, a rapid and persistent decrease in the number of CD20+ B cells, so with further administration of the drug, it will bind already with a much smaller amount of CD20+ cells. As a result, in subsequent ophatumumab administration, its ground clearance will be lower, and the value half-life - significantly higher than when it was first introduced; with repeated weekly administration of the value AUC and Cmax increased to a much greater extent than was expected for the expected accumulation of ofatumumab, calculated on the basis of data obtained at its first administration.

    Indications:

    Chronic lymphocytic leukemia.

    ICD-10

    II.C81-C96.C91.1   Chronic lymphocytic leukemia

    Contraindications:

    - severe kidney disease;

    - bSexuality, breast-feeding;

    - age to 18 years;

    - hypersensitivity.

    Carefully:

    - hepatitis B in the anamnesis;

    - impaired lung function;

    - heart disease.

    Pregnancy and lactation:

    Category FDA - C. The drug is contraindicated in pregnancy and lactation.

    Dosing and Administration:

    Intravenously, in the form of infusions.

    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, infusion of ophatumumab should be carried out in the conditions of immediate availability of equipment and medicines needed to provide emergency care in such situations.

    The recommended dose is 300 mg for the first administration, 2000 mg for subsequent administrations. The course is 8 weekly introductions. After a break of 4-5 weeks, the drug is administered 4 times at a frequency of 1 time per month.

    Side effects:

    From the respiratory system: shortness of breath, bronchospasm, cough, chest discomfort, hypoxia, nasal congestion, pain in the larynx / pharynx.

    From the gastrointestinal tract: an obstruction of an intestine, a nausea, a diarrhoeia.

    From the side of the blood: leukopenia, coagulopathy, agranulocytosis, neutropenia, febrile neutropenia, anemia, aplasia of erythrocyte sprout.

    From the immune system: anaphylactic shock, hypersensitivity.

    From the skin: rash, itching, hot flashes, hives.

    From the cardiovascular system: arterial hypertension, tachycardia, arterial hypotension.

    Other: secondary infections, chills, fatigue, tumor lysis syndrome, hyperhidrosis, hyperthermia, back pain, cytokine release syndrome.

    Secondary infections: very often - bronchitis, pneumonia; often - sepsis, septic shock, infection Herpes zoster, urinary tract infections; frequency unknown - progressive multifocal leukoencephalopathy, hepatitis B.

    Overdose:

    Not described.

    Interaction:

    When the drug is combined with drugs that have an immunosuppressive effect, it is possible to increase the likelihood of infectious diseases.

    Special instructions:

    During the application of the drug, it is necessary to have immediate access to the means for resuscitation and first aid in the case of anaphylaxis.

    Cardiovascular diseases

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

    Bowel obstruction

    In patients treated with anti-CD20 monoclonal antibodies, in particular ofatumum, the development of intestinal obstruction was sometimes noted.

    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

    Because the ofatumumab binds to all CD20-positive lymphocytes (both tumor and normal), during the treatment with ofatumum, hemogram monitoring is necessary at regular intervals; If patients develop cytopenia, the study should be done more often. With the development of cytopenia it is necessary to conduct appropriate therapy.

    Impact on the ability to drive vehicles and manage mechanisms

    Not found. When considering a patient's ability to perform actions that require an increased concentration of attention and speed of psychomotor reactions,should take into account its clinical status and profile of undesirable reactions of ofatumumab.

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