Vero-Cladribine (Vero-Cladribine)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceCladribineCladribine
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  • Vero-Cladribine
    solution d / infusion 
    VEROPHARM SA     Russia
    • Dosage form: & nbspconcentrate for solution for infusion
    Composition:

    Composition (per 1 ml of concentrate)

    Active substance:

    Cladribine - 1 mg

    Excipients:

    Sodium chloride 9 mg

    Potassium dihydrogen phosphate solution and sodium hydrogen phosphate solution to pH 6.3

    Water for injection up to 1 ml

    Description:

    Transparent colorless or slightly yellowish liquid.

    Pharmacotherapeutic group:Antitumour agent, antimetabolite
    ATX: & nbsp

    L.01.B.B.04   Cladribine

    Pharmacodynamics:

    Cladribine (2-chloro-2'-deoxyadenosine) is an analog of 2'-deoxyadenosine, which is part of the DNA molecule. Lymphoid cells are more sensitive to cladribine than non-lymphoid cells, since the former have a higher level of deoxycytidine kinase and a low level of 5'-nucleotidase activity. Cladribine has cytotoxic effects on fissionable and non-dividing cells, inhibiting DNA synthesis and repair.

    The cytotoxic effect is due to the action of the active metabolite - 5'-triphosphate of 2-chloro-2'-deoxyadenosine.

    The effect of the drug is associated with inhibition of ribonucleotide reductase, catalyzing the formation of deoxynucleoside triphosphates, necessary for DNA synthesis. The termination of DNA synthesis also occurs as a result of inhibition of the DNA polymerase.In addition, 5'-triphosphate of 2-chloro-2'-deoxyadenosine activates a specific endonuclease, which leads to single-strand breaks in the DNA. These phenomena are the cause of subsequent cell death.

    Pharmacokinetics:

    When administered intravenously, the half-life (T1/2) - from 5.7 to 19.7 hours. The concentration of the drug in the cerebrospinal fluid is 25% of its concentration in the plasma. The drug is mainly excreted in the urine (up to 35%), a small amount (less than 1%) is excreted with feces.

    The drug is subjected to intracellular metabolism. At the initial stage of phosphorylation to the 5'-monophosphate carries deoxycytidine. Since the level of deoxycytidine kinase activity is higher than that of 5'-nucleotidase, and also due to cladribine resistance to adenosine deaminase, all three phosphorylated forms of 2-chloro-2'-deoxyadenosine rapidly accumulate in the cell, including. 5'-triphosphate of 2-chloro-2'-deoxyadenosine.
    Indications:

    Hairy cell leukemia.

    Contraindications:

    Hypersensitivity to cladribine or any other component of the drug.

    Pregnancy and lactation.

    Children's age (safety and effectiveness of cladribine in children are not sufficiently studied).

    Carefully:PIn oppression of bone marrow function, kidney and / or liver failure, infectious complications of the underlying disease (the doctor must assess the risk-benefit relationship with the introduction of cladribine in patients with infectious complications), elderly.
    Dosing and Administration:

    Intravenously drip in the form of 2 hour or 24 hour infusion.

    Dosages and duration of treatment are determined by the attending physician depending on the characteristics of the course of the disease and the severity of the condition.

    The recommended dose is 0.09-0.1 mg / kg / day for 7 days. Usually only one course of therapy is given. Data on the increase in the antitumor effect in the course of additional courses are not available.

    Before the introduction, the necessary amount of concentrate is diluted in 0.5-1 L of a 0.9% solution of sodium chloride, while the infusion solution for long (24 hour) infusions uses a bacteriostatic 0.9% solution of sodium chloride (containing benzyl alcohol as a preservative).

    To prepare the infusion solution, it is not recommended to use a 5% dextrose solution due to the increased degradation of cladribine.

    Side effects:

    From the side of bone marrow hematopoiesis: leukopenia, neutropenia, thrombocytopenia, anemia, pancytopenia, anaplastic anemia, hemolytic anemia; very rarely - myelodysplastic syndrome.

    From the side of the digestive system: nausea, vomiting, anorexia, diarrhea, constipation, abdominal pain, increased bilirubin and / or transaminase levels.

    From the nervous system: headache, dizziness, insomnia, peripheral sensory neuropathies.

    From the side of the cardiovascular system: edema, tachycardia.

    From the respiratory system: cough, changes in percussion sound and auscultatory characteristics of breathing, rapid breathing, interstitial pneumonitis.

    From the skin and subcutaneous tissue: rash, skin peeling, skin itching, hives.

    From the musculoskeletal system: myalgia, arthralgia.

    Local Reactions: erythema, pain, swelling, thrombosis, phlebitis.

    Other: fever, weakness, asthenia, increased fatigue, pain of different locations, purpura, petechiae,nosebleeds, decreased immunity; predisposition to infections, opportunistic infections caused by Herpes simplex, Herpes zoster, Cytomegalovirus.

    Overdose:

    The use of high doses of cladribine was associated with the occurrence of irreversible neurotoxicity (paraparesis / tetraparesis), acute nephrotoxicity and severe oppression of bone hemopoiesis (neutropenia, anemia, thrombocytopenia).

    Treatment is symptomatic. The antidote to cladribine is not known.

    Interaction:

    When administered simultaneously or immediately after other myelotoxic drugs, additive inhibition of bone marrow function is possible.

    In the case of cladribine administration in high (exceeding standard) doses, in combination with cyclophosphamide and radiation therapy, neurotoxicity (irreversible para- and tetraparesis) and nephrotoxicity (acute renal failure) increase.

    Combination with allopurinol and antibiotics enhances skin rash.

    When mixed with a 5% solution of dextrose - increased degradation of cladribine.

    Special instructions:

    Treatment with cladribine should be carried out under the supervision of a doctor who has experience in the use of antitumor therapy.

    The myelosuppression observed during cladribine therapy is dose-dependent and usually reversible. The effects of myelosuppression of cladribine mainly appear within a month from the moment of treatment. During treatment and at least 4-8 weeks after, careful monitoring of blood hematologic parameters is necessary. Particular care should be taken in patients with initial oppression of bone marrow function of any origin because of the risk of prolonged hypoplasia.

    Treatment with cladribine can lead in some cases to severe forms of immunosuppression with a decrease in the level Cd4 white blood cells.

    If a febrile condition occurs against a background of neutropenia, careful monitoring of the general condition of patients during the first month of treatment and, if necessary, the appointment of antibiotic therapy, are necessary. In the case of neurotoxicity, treatment with the drug should be suspended until the resolution of neurological symptoms.

    Treatment of patients with renal and / or liver failure should be carried out under the direct control of kidney and liver function. Treatment should be discontinued in case of nephro- or hepatotoxicity.

    In the absence of data on pharmacokinetics in the elderly, careful monitoring of such patients is necessary.

    Form release / dosage:Concentrate for the preparation of solution for infusions, according to 10 mg / 10 ml (1 mg / ml).
    Packaging:

    10 ml in bottles.

    1 bottle with instructions for use in a pack of cardboard.

    For 6, 7 or 10 vials, together with instructions for use in a pack with partitions or special cardboard sockets.

    For 36 bottles with an equal number of instructions for use in a cardboard box (for hospitals).

    Storage conditions:

    In the dark place at a temperature of no higher than 8 ° C. Do not freeze.

    Keep out of the reach of children.
    Shelf life:

    3 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-002019/07
    Date of registration:09.08.2007 / 12.08.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia
    Manufacturer: & nbsp
    Information update date: & nbsp31.01.2017
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