Mitoxantrone (Mitoxantron)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMitoxantroneMitoxantrone
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    • Dosage form: & nbspconcentrate for solution for intravenous and intrapleural administration
    Composition:

    1 ml of concentrate contains:

    active substance: mitoxantrone hydrochloride 2.328 mg (mitoxantrone 2.00 mg);

    Excipients: acetic acid ice - 0.0053 ml, sodium acetate - 0.606 mg, sodium chloride - 4.34 mg, sodium disulfite 1.00 mg, water for injection - up to 1.00 ml

    Description:

    A dark blue liquid.

    Pharmacotherapeutic group:Antitumor agent - antimetabolite
    ATX: & nbsp

    L.01.D.B.07   Mitoxantrone

    L.01.D.B   Anthracyclines and related drugs

    Pharmacodynamics:

    Mitoxantrone is a cytostatic drug, a synthetic derivative of anthracenedione. It is embedded in DNA through hydrogen bonds, causing cross-linking and breaking of chains. Mitoxantrone It also interacts with RNA and is a potent topoisomerase inhibitor II (an enzyme responsible for the despiralization and repair of damaged DNA). Has a cytotoxic effect on both dividing and non-dividing cells (lack of phase-specificity).

    In vitro inhibits the proliferation of B- and T-lymphocytes and macrophages, disrupts the recognition of antigens, the secretion of interferon gamma, tumor necrosis factor alpha and interleukin.

    Pharmacokinetics:

    After intravenous administration mitoxantrone quickly penetrates and is distributed in tissues, from which then its gradual release occurs. It is found in high concentrations in the liver, lungs and in descending order: in the bone marrow, heart, thyroid gland, spleen, pancreas, in the adrenal gland and kidney.

    The volume of distribution reaches 1000 l / m 2. Does not penetrate the blood-brain barrier.

    Connection with blood plasma proteins - 90%. The mitoksantrone pharmacokinetics after a single intravenous administration can be characterized as a three-phase model: mean T1/2 alpha - 6-12 min, medium T1/2 beta - 1.1-3.1 h, medium T1/2 gamma - 23-215 h (an average of 75 h). Metabolised in the liver. Within 5 days of excretion from the bile is derived from 13,6% to 24,8% and with the kidney from 5,2% to 7,9% mitoxantrone.

    In patients with impaired liver function, there was a decrease in the rate of elimination of mitoxantrone.

    Indications:

    - Acute non-lymphoblastic leukemia in adults;

    - mammary cancer;

    - malignant non-Hodgkin's lymphomas;

    - primary hepatocellular carcinoma;

    - ovarian cancer;

    - hormone-resistant prostate cancer with pain syndrome.
    Contraindications:

    - Hypersensitivity to mitoxantrone or other components of the drug;

    - the neutrophil count is less than 1500 / μl (excluding the treatment of non-lymphoblastic leukemia);

    - pregnancy and the period of breastfeeding;

    - age to 18 years.

    Carefully:

    Pexchange mitoxantrone in patients with heart diseases (including acute period of myocardial infarction, decompensated CHF, tachysystolic forms of arrhythmia, severe angina), with previous mediastinal irradiation, with oppression of hematopoiesis, with marked violations of the liver or kidney function, with bronchial asthma, with acute infectious diseases of the viral (including chicken pox, shingles), fungal or bacterial nature (risk of severe complications and generalization of the process), with diseases in which there is an increased risk of hyperuricemia (gout or urate nephrolithiasis) and in patients who had previously received anthracyclines.

    Dosing and Administration:

    A drug Mitoxantrone is included in many chemotherapy regimens, therefore, when choosing the route of administration, regimen and dosage in each individual case, reference should be made to the literature.

    The drug is administered intravenously slowly, for at least 5 minutes or intravenously drip for 15-30 minutes. Preferably administer the drug Mitoxantrone into the tube of the infusion system slowly against a background of rapid infusion with 0.9% sodium chloride solution or 5% dextrose solution. The drug can be administered intrapleurally.

    Intrathecal, intraarterial, intramuscular, subcutaneous injection of the drug is prohibited!

    The maximum total dose of the drug Mitoxantrone - 200 mg / m2 surface of the body.

    In breast cancer, non-Hodgkin's lymphoma, primary hepatic-cell carcinoma and ovarian cancer in the monotherapy of the drug Mitoxantrone used in a dose of 14 mg / m2 1 time in 3 weeks. In patients who received chemotherapy earlier, and also when combined with other antitumour agents, the dose of the drug is reduced to 10-12 mg / m2. With repeated courses of dose of the drug Mitoxantrone are selected taking into account the degree of severity and duration of oppression of bone marrow hematopoiesis.

    In case of a decrease in the number of neutrophils at previous courses <1500 and / or platelets <50,000 cells / μl of blood, the dose of the drug Mitoxantrone decreases by 2 mg / m2, with a decrease in the number of neutrophils <1000 and / or platelets <25,000 cells / μl of blood subsequent doses of the drug Mitoxantrone decrease by 4 mg / m2.

    In the treatment of acute non-lymphoblastic leukemia in adults for remission induction remedy Mitoxantrone prescribe in a dose of 10-12 mg / m2 daily for 5 days to a total dose of 50-60 mg / m2. It is possible to administer high doses of the drug Mitoxantrone - 14 mg / m2 and more daily for 3 days.

    For treatment hormone-resistant prostate cancer with pain syndrome drug Mitoxantrone prescribe in a dose of 12-14 mg / m2 1 every 21 days in combination with daily intake of low doses of glucocorticosteroids (prednisolone 10 mg / day or hydrocortisone 40 mg / day).

    When intrapleural instillation with metastases in the pleura (for breast cancer and non-Hodgkin's lymphomas) the recommended single dose is 20-30 mg. For intrapleural instillation, the drug Mitoxantrone dilute in 50 ml of 0.9% solution of sodium chloride. Before the beginning of therapy evacuate, whenever possible, pleural exudate. A drug Mitoxantrone, diluted in 50 ml of 0.9% sodium chloride solution, warmed to body temperature and injected slowly for 5-10 minutes. Exposure period of the preparation Mitoxantrone in the pleural cavity is 48 hours. During this period, patients should move to ensure optimal intrapleural distribution of the drug. After this time (48 hours), the pleural cavity is re-drained. If the amount of effusion is less than 200 ml, the first treatment cycle is stopped. If the amount of effusion is greater than 200 ml, a repeated instillation of 30 mg of the drug Mitoxantrone. Before carrying out the repeated instillation of the drug, hematological parameters should be monitored. The second dose of the drug Mitoxantrone can remain in the pleural cavity. The maximum dose for one treatment cycle is 60 mg. If the number of neutrophils and platelets is within normal limits, intrapleural instillation can be repeated after 4 weeks.

    For 4 weeks before and 4 weeks after intrapleural administration of the drug Mitoxantrone should avoid systemic cytotoxic therapy.

    Side effects:

    On the part of the hematopoiesis system, leukopenia (usually on day 6-15, recovery on day 21): neutropenia, thrombocytopenia, erythrocytopenia, rarely anemia.

    From the digestive system: nausea, vomiting, anorexia, decreased appetite, diarrhea, abdominal pain, constipation, gastrointestinal bleeding, stomatitis, increased activity of "liver" transaminases, impaired liver function.

    From the side of the cardiovascular system: changes in the ECG, tachycardia, arrhythmia, myocardial ischemia, reduction of the fraction of the left ventricle ejection, congestive heart failure. Toxic myocardial damage, in particular chronic heart failure (CHF), can develop both during treatment with mitoxantrone, and in months and years after the end of therapy. The risk of a cardiotoxic effect increases when the total dose is 140 mg / m2.

    On the part of the respiratory system: cases of interstitial pneumonitis are described.

    Allergic reactions: pruritus, rash, hives, lowering of blood pressure, dyspnea, anaphylactic reactions (including anaphylactic shock).

    Local Reactions: phlebitis; when extravasation - erythema, swelling, pain, burning, necrosis of surrounding tissues. Cases of intense blue staining of veins, into which the preparation was administered and surrounding tissues, are described.

    Other: alopecia, fatigue, general weakness, fever, nonspecific neurological symptoms, back pain, headache, menstrual disorder, amenorrhea, blue skin and nail coloration, nail dystrophy and reversible blue staining of sclera, secondary infections, hyperuricemia, hypercreatininaemia .

    Overdose:

    In case of an overdose, it is possible to intensify, primarily, myelotoxicity and the above-mentioned dose-dependent side effects, the occurrence of dyspnea, an increase in the concentration of urea in the blood.

    The use of dialysis is ineffective. AT In case of overdose, careful monitoring of the patient should be established and, if necessary, symptomatic therapy should be provided. The specific antidote for mitoxantrone is not known.

    Interaction:

    - Pharmaceutical: Do not mix the drug with other agents (with the exception of 0.9% solution of sodium chloride or 5% solution of dextrose) with intravenous administration (mayprecipitation occurs).

    - Pharmacodynamic: a drug Mitoxantrone potentiates the effect of many cytotoxic drugs, such as cytarabine, cisplatin, cyclophosphamide, fluorouracil, methotrexate, vincristine, dacarbazine.

    - With the simultaneous use of the drug Mitoxantrone with other antitumour agents or irradiation of the mediastinal region, it is possible to increase its cardio- and myelotoxicity.

    - Simultaneous use of drugs blockinganalEgg secretion (including uricosuric antidotal drugs - sulfinpyrazone), may increase the risk of developing nephropathy.

    - In connection with the immunosuppressive effect of the drug and the possibility of developing severe infections, it is not recommended during chemotherapy to apply live vaccine.

    - Pharmacokinetic: there were no dangerous interactions with other drugs.

    Special instructions:

    Treatment with mitoxantrone should be performed under the supervision of a doctor who has experience with antitumor drugs.

    In the process of treatment, a systematic control of the pattern of peripheral blood is necessary, (before each introduction, a complete blood test,including platelet counts), laboratory parameters of liver function as well as activity of the heart (electrocardiogram, echocardiogram with the determination of left ventricular ejection fraction (LVEF)). After reaching the total dose of mitoxantrone in 100 mg / m2 determination of LVEF values ​​should be made before each next injection. Cardiovascular disease in the active or inactive phase, radiotherapy to the mediastinal area / pericardial area, previous held or carried out simultaneously with the treatment of mitoxantrone prior treatment with other anthracyclines or anthracenediones, as well as concomitant treatment with other cardiotoxic drugs may increase the risk of toxic damage to the heart. The risk of cardiotoxicity increases when the total dose of mitoxantrone exceeds 140 mg / m2, however, toxic heart damage can develop at lower total doses of the drug.

    In the treatment of leukemia, hyperuricemia may occur as a result of rapid disintegration of tumor cells. If necessary, hypouricemic drugs should be prescribed.

    In the case of extravasation, it is necessary to stop the administration of the drug and, if necessary, continue the infusion into another vein.

    The use of topoisomerase II inhibitors, including mitoxantrone, in combination with other antitumor drugs and / or radiotherapy, can lead to the development of acute myeloblastic leukemia (AML) or myelodysplastic syndrome (MDS).

    Women and men during treatment with mitoxantrone, and also within 6 months after its withdrawal should use reliable methods of contraception.

    Avoid contact with the skin or mucous membranes; possibly the emergence of tissue necrosis. The skin, in case of contact with the drug, must be thoroughly rinsed with warm water.

    The drug reduces the effectiveness of vaccination. Vaccination should be carried out 3 months after the completion of therapy.

    Effect on the ability to drive transp. cf. and fur:

    During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Concentrate for the preparation of a solution for intravenous and intrapleural administration, 2 mg / ml.

    Packaging:

    For 20 mg / 10 ml of the drug in orange glass vials, sealed with rubber plugs of gray color and a capsule of the "flip-top"(an aluminum capsule of silver color with a disc of red plastic). each bottle stick the label.

    1 bottle with instructions for use in a cardboard box.

    Storage conditions:

    Store in a dark place at a temperature of 5 to 25 ° C. Do not freeze.

    Keep out of the reach of children.

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:П N013628 / 01
    Date of registration:23.07.2010 / 23.12.2013
    Expiration Date:Unlimited
    The owner of the registration certificate:VALEANT, LLC VALEANT, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspVALEANT LLC VALEANT LLC Russia
    Information update date: & nbsp09.06.2018
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