Trastuzumab emtanzine (Trastuzumab emtansine)

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
  • Kadsila®
    lyophilizate d / infusion 
    Hoffmann-La Roche Ltd.     Switzerland
    • АТХ:

    L.01.X.C.14   Trastuzumab emtanzine

    Pharmacodynamics:

    Complex preparation, the activating antibody dependent cytotoxicity in tumor cells in cancer human breast, accompanied by overexpression of epidermal growth receptor type 2 (HER2).

    Trastuzumab

    The humanized monoclonal antibody exerts a cytostatic effect on cells expressing the transmembrane glycoprotein from the family of epidermal growth receptors of type 2 (HER2).

    Has a high affinity for the receptors of epidermal growth factor, which is a transmembrane glycoprotein from the family of Type I tyrosine kinase receptors. The epidermal growth factor receptor stimulates the growth of normal epithelial cells and is expressed on tumor cells.

    It binds to the ligand-binding domain of epithelial growth factor, as a result of which it inhibits autophosphorylation processes induced by transmembrane glycoproteins from the family of tyrosine kinase receptors of type 1, which leads to inhibition of cell growth, decrease in the production of vascular endothelial growth factor, interleukin-8, induction of apoptosis.

    The maytansine derivative

    It is released after proteolytic degradation of trastuzumab emtansine in lysosomes of tumor cells, which determines the selective cytotoxicity of the drug against cells with overexpression HER2. Inhibits the polymerization of tubulin, blocking the cell cycle in the phase G2M, which leads to apoptosis.

    Pharmacokinetics:

    After intravenous infusion, the elimination half-life is 4 days. Elimination with bile and kidney.

    Indications:

    It is used for the treatment of metastatic breast cancer. Used as a monotherapy after previous chemotherapy with taxanes in combination with trastuzumab or with disease progression for 6 months after adjuvant treatment, as well as in patients with metastatic or locally advanced inoperable HER2-positive breast cancer.

    ICD-10

    II.C50   Malignant neoplasm of breast)

    Contraindications:

    Interstitial pneumonitis, nodular regenerative liver hyperplasia, severe cardiac (myocardial infarction, unstable angina), hepatic and renal failure, individual intolerance, children under 18 years of age.

    Carefully:

    Thrombocytopenia, blood clotting disorders, acute infectious diseases, hypersensitivity.

    Pregnancy and lactation:

    Recommendations for FDA - Category X. Contraindicated in pregnancy. Contraindicated breastfeeding during treatment, and also within 7 months after the end of chemotherapy.

    Dosing and Administration:

    Intravenously infuzionalno at 3.6 mg / kg 1 every 3 weeks for 1 hour, with a dose of more than 1 g - for 1.5 hours.

    The highest daily dose: 3.6 mg / kg.

    The highest single dose: 3.6 mg / kg.

    Side effects:

    Central and peripheral nervous system: asthenia, headache, insomnia, dizziness, peripheral neuropathy, cognitive impairment.

    Hematopoietic system: thrombocytopenia.

    The cardiovascular system: dysfunction of the left ventricle, epistaxis, arterial hypertension.

    Respiratory system: shortness of breath, cough, rarely pneumonitis.

    Digestive system: stomatitis, nausea, diarrhea, constipation, abdominal pain, vomiting, bleeding gums.

    Musculoskeletal system: arthralgia, myalgia.

    Dermatological reactions: acne-like dermatitis, exfoliative rash, hirsutism, paronychia, hypertrichosis, alopecia, palmar-plantar erythrodysesthesia, impaired nail structure.

    Sense organs: dry eyes, conjunctivitis, irritation and hyperemia of the eyes, blurred vision.

    Urinary system: urinary tract infections.

    Allergic reactions.

    Overdose:

    Thrombocytopenia, diarrhea, dehydration, increased skin reactions.

    Treatment is symptomatic.

    Interaction:

    Contraindicated concurrent use with calcium folinate, irinotecan, fluorouracil (increased toxicity).

    Special instructions:

    The purpose of the drug is possible only with laboratory confirmation of the presence of tumor expression of the protein HER2.

    Monitoring the content of plasma electrolytes.

    If there is and progression of interstitial lung diseases should be canceled application of the drug.

    In the treatment it is not recommended to drive vehicles and work with moving mechanisms.

    Instructions
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