Mitoxantrone - Instructions For Use, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Mitoxantrone

Mitoxantrone: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Mitoxantron

ATX code: L01DB07

Active ingredient: mitoxantrone (mitoxantrone)

Producer: Pharmstandard Biolek (Russia), Lance-Pharm LLC (Russia), Thymoorgan GmbH Pharmazie & Co. KG (Germany), Waet-Lederle (Great Britain)

Description and photo update: 15.06.2018

Mitoxantrone is an antineoplastic drug, an antimetabolite.

Release form and composition

The dosage form of Mitoxantrone is a concentrate for the preparation of a solution for intravenous (IV) and intrapleural administration: dark blue liquid (in vials from a glass tube of 5 ml, in glass vials of 5, 10 or 15 ml; in a cardboard box of 10 vials 5 or 10 ml, 1 bottle of 5, 10 or 15 ml).

Composition of 1 ml of concentrate:

• active substance: mitoxantrone hydrochloride - 0.002 328 g (corresponds to the content of mitoxantrone - 0.002 g);
• auxiliary components: water for injection - up to 1 ml; sodium disulfite - 0.001 g; sodium chloride - 0.004 34 g; sodium acetate - 0.000 606 g; glacial acetic acid - 0.0053 ml.

Pharmacological properties

Pharmacodynamics

Mitoxantrone is a cytostatic agent, a synthetic derivative of anthracenedione. Through hydrogen bonds, it is incorporated into deoxyribonucleic acid (DNA), which causes cross-linking and chain breaking. It also interacts with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II. Mitoxantrone has a cytostatic effect on dividing and non-dividing cells.

According to in vitro data, mitoxantrone disrupts the secretion of tumor necrosis factor alpha and interleukin, interferon gamma, antigen recognition, inhibits the proliferation of B- and T-lymphocytes, and macrophages.

Pharmacokinetics

After intravenous administration, mitoxantrone quickly enters the body and is distributed in the tissues, from where it is then gradually released. In high concentrations, the substance is found in the lungs, liver and in ascending order: in the kidneys, adrenal glands, pancreas, spleen, thyroid gland, heart and bone marrow. Its volume of distribution reaches 1000 liters per 1 m ². It does not penetrate the blood-brain barrier.

The connection with blood plasma proteins is 90%.

After a single intravenous administration, the pharmacokinetics of mitoxantrone can be characterized as a three-phase model:

• average T _1/2 (half-life) α: varies from 6 to 12 minutes;
• average T _1/2 β: varies from 1.1 to 3.1 hours;
• average T _1/2 γ: varies from 23 to 215 hours (75 hours on average).

The metabolism of the substance is carried out in the liver. For 5 days, 13.6–24.8% of mitoxantrone is excreted in the bile, 5.2–7.9% of mitoxantrone is excreted in the kidneys.

With impaired liver function, the rate of elimination of mitoxantrone decreases.

Indications for use

• cancer: breast, ovarian, primary hepatocellular carcinoma, hormone-resistant prostate cancer with pain syndrome;
• acute non-lymphoblastic leukemia (in adult patients);
• malignant non-Hodgkin lymphomas.

Contraindications

Absolute:

• the content of neutrophils is less than 1500 per 1 μl (the exception is the therapy of non-lymphoblastic leukemia);
• age under 18;
• pregnancy and lactation;
• individual intolerance to the components contained in the drug.

Relative (diseases / conditions in the presence of which the appointment of Mitoxantrone requires caution):

• severe liver or kidney dysfunction;
• bronchial asthma;
• heart disease, including severe angina pectoris, tachysystolic arrhythmias, decompensated chronic heart failure, acute period of myocardial infarction;
• oppression of hematopoiesis;
• acute infectious pathologies of a viral (including chickenpox, shingles), fungal or bacterial origin (due to the risk of severe complications and generalization of the process);
• previous irradiation of the mediastinum;
• pathologies, against the background of which there is an increased risk of developing hyperuricemia (gout or urate nephrolithiasis);
• previous therapy with anthracyclines.

Instructions for use of Mitoxantrone: method and dosage

The solution prepared from the concentrate is injected intrapleurally, intravenously slowly over 5 minutes (at least), or intravenously drip over 15-30 minutes. It is preferable to slowly inject the drug into the tube of the infusion set with a rapid infusion of 5% dextrose solution or 0.9% sodium chloride solution.

Mitoxantrone is used in many chemotherapeutic treatment regimens, therefore, when choosing the route of administration and dosage regimen, they are individually guided by the data of special literature.

It is forbidden to inject the drug subcutaneously, intramuscularly, intraarterially or intrathecally.

The total maximum dose of the solution is 0.2 g per 1 m ² of body surface.

Recommended dosage regimen:

• ovarian cancer, breast cancer, non-Hodgkin's lymphomas, primary hepatocellular carcinoma (monotherapy): 0.014 g per 1 m ² 1 time per day for 21 days. The dose of the drug in patients who previously received chemotherapy, as well as when combined with other anticancer drugs, is reduced to 0.01–0.012 g per 1 m ². With repeated courses, the selection of the dose of the drug is carried out taking into account the severity and duration of the inhibition of bone marrow hematopoiesis;
• acute non-lymphoblastic leukemia (for the purpose of inducing remission): 0.01–0.012 g per 1 m ² per day for 5 days to a total dose of 0.05–0.06 g per 1 m ². Allowed the introduction of high doses of the drug - 0.014 g per 1 m ² or more per day for 3 days;
• hormone-resistant prostate cancer with pain syndrome: 0.012–0.014 g per 1 m ² once every 21 days in combination with daily intake of glucocorticosteroids in low doses (0.01 g of prednisolone or 0.04 g of hydrocortisone per day);
• metastases in the pleura against the background of breast cancer and non-Hodgkin's lymphomas: the drug is administered through intrapleural instillations in a single dose of 0.02–0.03 g. Before use, Mitoxantrone is diluted in 50 ml of 0.9% sodium chloride solution. Pleural exudate should be evacuated as far as possible before starting treatment. In a diluted form, the drug is warmed to body temperature and injected slowly over 5-10 minutes. The period of its exposure in the pleural cavity is 48 hours, during which the patient must move in order to ensure optimal intrapleural distribution of the agent. After 48 hours, the pleural cavity is re-drained. The first cycle of therapy is stopped if the amount of effusion is 200 ml. Repeated instillation of 0.03 g of the drug is prescribed when the amount of effusion is> 200 ml. Before the introduction of re-instillation, hematological parameters are monitored. The second dose of Mitoxantrone may remain in the pleural space. For one cycle of therapy, the maximum dose of the drug is 0.06 g. It is possible to carry out repeated intrapleural instillation after 28 days, if the number of neutrophils and platelets is within normal limits. Within 28 days before and 28 days after intrapleural administration of the drug, it is important to avoid systemic treatment with cytostatics. Within 28 days before and 28 days after intrapleural administration of the drug, it is important to avoid systemic treatment with cytostatics. Within 28 days before and 28 days after intrapleural administration of the drug, it is important to avoid systemic treatment with cytostatics.

With a decrease in the number of neutrophils against the background of previous courses <1500 and / or platelets <50,000 cells per 1 μl of blood, the dose of the drug is reduced by 0.002 g per 1 m ²; if the number of neutrophils is <1000 and / or platelets <25000 cells per 1 μl of blood, subsequent doses of the drug are reduced by 0.004 g per 1 m ².

Side effects

Possible adverse reactions (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):

• hematopoietic system: leukopenia, erythrocytopenia, thrombocytopenia, neutropenia; rarely - anemia;
• digestive system: impaired liver function, increased activity of hepatic transaminases, vomiting, nausea, stomatitis, gastrointestinal bleeding, constipation, abdominal pain, diarrhea, decreased appetite, anorexia;
• cardiovascular system: congestive heart failure, decreased left ventricular ejection fraction, myocardial ischemia, arrhythmias, tachycardia, changes in the electrocardiogram; during the period of therapy, as well as months and years after its end, the development of toxic damage to the myocardium, in particular chronic heart failure, is possible;
• respiratory organs: interstitial pneumonitis;
• allergic reactions: anaphylactic reactions, including anaphylactic shock, shortness of breath, decreased blood pressure, urticaria, skin rash, itching;
• local reactions: phlebitis; with extravasation - necrosis of surrounding tissues, burning, pain, edema, erythema; there are reports of intense staining of the veins into which the drug was injected and the tissues surrounding them in blue;
• others: hypercreatininemia, hyperuricemia, secondary infections, reversible blue staining of the sclera, dystrophy of nails, blue staining of the skin and nails, amenorrhea, menstrual irregularities, headache, back pain, nonspecific neurological symptoms, fever, general weakness, increased fatigue, alopecia.

Overdose

The main symptoms: increased, first of all, myelotoxicity and dose-dependent side effects of the drug, an increase in the concentration of urea in the blood, the development of shortness of breath.

Therapy: careful monitoring of the patient's condition, symptomatic treatment (if necessary).

special instructions

Drug therapy should be carried out under the supervision of a physician who has experience with antineoplastic agents.

During the treatment period, the peripheral blood picture is systematically monitored (before each administration, a complete blood count is mandatory, including platelet count), laboratory indicators of liver function, heart activity (electrocardiogram, echocardiography with determination of the left ventricular ejection fraction). Upon reaching the total dose of the drug 0.1 g per 1 m ^{2, the} determination of the values for determining the ejection fraction of the left ventricle is mandatory before each next administration of Mitoxantrone.

An increased risk of toxic heart damage is possible in the following cases:

• cardiovascular pathology in an active or inactive phase;
• radiation therapy to the pericardial or mediastinal region, previously or in combination with mitoxantrone treatment;
• previous treatment with other anthracyclines or anthracenediones;
• concomitant treatment with other cardiotoxic drugs.

The risk of cardiotoxicity increases when the total dose of the drug is exceeded by 0.14 g per 1 m ², but toxic damage to the heart is possible even at lower total doses.

In cases of leukemia therapy, hyperuricemia may develop as a result of the rapid disintegration of tumor cells. If necessary, the appointment of hypouricemic drugs is recommended.

With extravasation, the administration of the drug is stopped, and the infusion, if necessary, is continued into another vein.

It is important to take into account that the use of topoisomerase II inhibitors, including mitoxantrone, in combination with other antineoplastic agents and / or radiation therapy, may lead to the development of acute myelodysplastic syndrome or myeloblastic leukemia.

During the period of drug treatment, as well as for months after its termination, it is recommended to use reliable methods of contraception.

It is important to avoid contact of the drug with mucous membranes or skin, as tissue necrosis is possible. In case of accidental contact, the skin is thoroughly washed with warm water.

Since Mitoxantrone reduces the effectiveness of vaccination, it is possible to carry it out only 3 months after the end of treatment with the drug.

Influence on the ability to drive vehicles and complex mechanisms

Patients during the period of therapy should be careful when driving or conducting potentially hazardous activities.

Application during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation.

Pediatric use

According to the instructions, Mitoxantrone is contraindicated in children under the age of 18.

With impaired renal function

The drug is prescribed with caution to patients with severe renal impairment.

For violations of liver function

Mitoxantrone is used with caution in severe liver dysfunction.

Drug interactions

When administered intravenously, mitoxantrone cannot be mixed with other solutions, since precipitation is possible, with the exception of 5% dextrose solution or 0.9% sodium chloride solution.

Mitoxantrone when combined with dacarbazine, vincristine, methotrexate, fluorouracil, cyclophosphamide, cisplatin, cytarabine and other cytotoxic drugs potentiates their action.

An increase in the cardio- and myelotoxicity of mitoxantrone is possible with its combined use with other anticancer drugs or irradiation of the mediastinal region.

With the simultaneous use of mitoxantrone with drugs that block tubular secretion, including uricosuric anti-gout agents (sulfinpyrazone), the risk of developing nephropathy may increase.

Since the drug has an immunosuppressive effect and can cause severe infections, it is not recommended to use live vaccines during chemotherapy.

No dangerous interactions of mitoxantrone with other medicinal substances / preparations used simultaneously were found.

Analogs

Mitoxantrone analogs are: Oncotron, Mitoxantrone-LENS.

Terms and conditions of storage

Store in a place protected from light and moisture at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Mitoxantrone

According to reviews, long-term use of Mitoxantrone (over 2 years) effectively reduces the number of relapses and the rate of increase in neurological symptoms. In general, reviews about the effectiveness of the drug are ambiguous, because it can be assessed no earlier than after 1 year from the start of using the drug or at the end of the course of treatment. Among the disadvantages, the development of complications from the heart and the risk of female infertility are noted.

Price for Mitoxantrone in pharmacies

The approximate price of Mitoxantrone concentrate (10 ml in vials) is 2360 rubles.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!