Belimumab (Belimumabum)

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

Immunosuppressive drugs

Included in the formulation
  • Benlist®
    lyophilizate d / infusion 
    GlaxoSmithKline SpA     Italy
    • АТХ:

    L.04.A   Immunosuppressive drugs

    Pharmacodynamics:

    Belimumab is a stimulator of B-lymphocytes (BLyS, also known as BAFF and TNFSF13). It belongs to the group of ligands of the family of tumor necrosis factor (TNF). Has suppressive apoptosis of B-lymphocytes and stimulates the differentiation of B-lymphocytes into plasma cells that produce immunoglobulin.

    Excess expression of BLyS is observed in patients with systemic lupus erythematosus (SLE). There is a correlation between the degree of SLE activity and the level of BLyS in the blood plasma. Belimumab - fully human monoclonal antibodies of class IgGλ, which specifically bind to soluble human BLyS and inhibit its biological activity. Belimumab binds to B-lymphocytes indirectly, but by binding to BLyS belimumab suppresses the viability of B-lymphocytes, incl. autoreactive clones, and reduces the differentiation of B-lymphocytes into plasma cells that produce immunoglobulin.


    Pharmacokinetics:

    After intravenous administration of belimumab at a dose of 10 mg / kg, the maximum concentration of substance in blood plasma leaves 313 μg / ml.

    Area under the kinetic curve (area under curve) "concentration - time" - 3,083 days × μg / ml

    Half-life in the phase of distribution - 1,75 days

    Half-life in the terminal phase - 19.4 days

    Systemic clearance - 215 ml per day, Vss - 5.29 l.


    Indications:

    Treatment of systemic lupus erythematosus in the active phase in the presence of autoantibodies - in adults receiving standard therapy.

    ICD-10

    XIII.M30-M36.M32   Systemic lupus erythematosus

    Contraindications:

    Increased sensitivity of the body to belimumab and the components of the drug.

    Carefully:

    With caution should decide on the use of belimumab in patients with chronic infections, as well as in patients receiving any therapy for chronic infections.

    It is necessary to consider the possibility of interrupting the treatment with belimumab in the case of a new infection with the treatment with belimumab and carefully monitor the condition of these patients.

    Caution should be applied belimumab in elderly patients.

    Pregnancy and lactation:

    The safety of the use of belimumab during pregnancy and lactation (breastfeeding) has not been studied.

    Adequate and strictly controlled clinical studies of belimumab in pregnant women were not conducted. Antibodies to immunoglobulin G, incl.to belimumab, are able to penetrate the placental barrier. The use of belimumab in pregnancy is possible only in cases where the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

    Women of childbearing age should use reliable contraceptive methods during treatment with belimumab and at least 4 months after the end of therapy. Patients should inform the doctor of the planned or onset of pregnancy, as well as the planned breastfeeding.

    Influence on fertility has not been studied.

    If you need to use belimumab during lactation, breastfeeding should be discontinued.

    AT experimental research shown, that belimumab penetrates the placental barrier in monkeys of the genus Synomolgus. No direct or indirect teratogenic effect was observed. No cases of death of the fetus or newborn were noted. The significance of this data for a person is unknown. In the monkeys belimumab excreted in breast milk.

    Dosing and Administration:

    Enter by intravenous infusion.

    The recommended dose is 10 mg / kg with an interval of 2 weeks with the first three infusions, with subsequent infusions the interval is 4 weeks.

    With the development of infusion reactions, the rate of administration should be reduced or interrupted by infusion.

    When developing severe reactions of hypersensitivity, the infusion should be discarded.

    Prior to the administration of belimumab, premedication should be performed to avoid infusion reactions and hypersensitivity reactions.

    Side effects:

    Immunological reactions: antibodies against belimumab can not be excluded (clinical significance is unknown).

    Allergic reactions: in postmarketing observations, anaphylactic reactions with a lethal outcome were noted.

    From the digestive system: nausea, diarrhea, viral infections of the gastrointestinal tract.

    From the respiratory system: nasopharyngitis, bronchitis, pharyngitis.

    From the nervous system: insomnia, depression, migraine.

    Common reactions: pyrexia, pain in the limbs.

    Other: cystitis, and leukopenia.

    Overdose:

    Treatment is symptomatic. There is no special antidote.

    Interaction:

    There were no special studies of the drug interaction of belimumab.

    The influence of belimumab on the pharmacokinetics of other drugs has not been studied.

    In clinical studies in patients who received standard therapy for systemic lupus erythematosus, belimumab were administered in combination with other drugs, including corticosteroids, antimalarial drugs, immunomodulators and immunosuppressants, incl. azathioprine, methotrexate, mycophenolate, antihypertensives, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, HMG-CoA reductase inhibitors (statins), and non-steroidal anti-inflammatory drugs; while no clinically significant effects of these drugs on the pharmacokinetics of belimumab.

    Special instructions:

    The efficacy of belimumab in patients with severe active lupus nephritis or severe lupus erythematosus of the central nervous system has not been established. The effectiveness of belimumab in combination with other biological preparations or with cyclophosphamide (intravenously) has not been studied. The use of belimumab in such cases is not recommended.

    In clinical studies, mortality with the use of belimumab was comparable to that in placebo. The causes of deaths were infections, cardiovascular diseases and suicide.

    Belimumab should be administered under conditions that allow emergency treatment if allergic, anaphylactic and infusion reactions develop.

    Against the background of the use of belimumab, side reactions from the psyche (severe depression, suicidal behavior) in most cases were observed in patients with a history of depression or other serious mental disorders; these patients in most cases received psychotropic drugs. It is not known whether belimumab risk of these disorders.

    Patients receiving belimumab, should be warned about the need to consult a doctor with worsening depression, suicidal thoughts or mood changes.

    Live vaccines should not be administered 30 days before and during treatment with belimumab, clinical safety of simultaneous application is not established.

    There is no data on the possibility of secondary infection of patients receiving belimumab, from people who have been injected with live vaccines, or about the effect of belimumab on new immunizations. Given the mechanism of action, belimumab may interfere with the development of an immune response.

    There were no cases of malignancy with the use of belimumab.

    Belimumab is not recommended to be combined with biological medications or cyclophosphamide for intravenous administration.

    Long-term preclinical studies on the carcinogenicity of belimumab were not conducted. The mutagenic potential of belimumab was not evaluated.

    Use in Pediatrics

    The safety and effectiveness of the use of belimumab in children have not been studied.

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