Vorinostat (Vorinostatum)

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

Antineoplastic agents

Included in the formulation
  • Zolinza®
    capsules inwards 
    Merck Sharp and Doum B.V.     Netherlands
    • АТХ:

    L.01.X.X.38   Vorinostat

    Pharmacodynamics:

    Inhibits histone-deacetylase class I (HDAC1, HDAC2 and HDAC3) and class II (HDAC6), resulting in the accumulation of acetyl groups on histone-lysine radicals, which leads to chromatin spreading. Violation of the cell cycle leads to apoptosis.

    Pharmacokinetics:

    After ingestion, up to 33% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 2 hours. The connection with plasma proteins is 71%.

    Metabolism in the liver with the formation of two metabolites: O-glucuronide vorinostat and 4-anilino-4-oxobutanoic acid.

    The half-life of vorinostat and O-glucuronic metabolite is 2 hours, 4-anilino-4-oxobutanoic acid is 11 hours. Elimination with feces.

    Indications:It is used to treat T-cell lymphoma, resistant to systemic therapy.

    ICD-10

    II.C81-C96.C84   Peripheral and cutaneous T-cell lymphomas

    Contraindications:Hepatic and renal failure, expressed myelosuppression, individual intolerance, children under 18 years of age.

    Carefully:

    Thrombocytopenia, leukopenia, hypoalbuminemia, hypersensitivity.

    Pregnancy and lactation:

    Recommendations for FDA - category D. Contraindicated in pregnancy and lactation.

    Dosing and Administration:

    Inside, 400 mg once a day after meals. It is possible to reduce the dose to 300 mg in case of intolerance.

    The highest daily dose: 400 mg.

    The highest single dose: 400 mg.

    Side effects:

    Central and peripheral nervous system: fatigue, dizziness, headache, syncope.

    Hemopoietic system: anemia, thrombocytopenia, and leukopenia.

    Respiratory system: cough, rapid breathing, lobar pneumonia, pulmonary embolism.

    The cardiovascular system: phlebitis, thrombophlebitis, myocardial infarction, ischemic stroke.

    Digestive system: dry mouth, anorexia, nausea, rarely - melena, diarrhea.

    Musculoskeletal system: muscle spasms, spinal cord injury.

    urinary system: nephropathy, proteinuria, obstruction of the urinary tract.

    Dermatological reactions: alopecia, itching, exfoliative dermatitis.

    Allergic reactions.

    Overdose:

    Increased side effects.

    Treatment is symptomatic.

    Interaction:

    Enhances the effects of anticoagulants.

    With simultaneous use with valproic acid, thrombocytopenia develops, which leads to bleeding in the gastrointestinal tract.

    Special instructions:

    The use of vorinostat should be discontinued two weeks before the planned surgical intervention.

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

    Instructions
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