Oncotrone, vial 2mg/ml, 10ml

Composition

1 ml of concentrate contains:

Active ingredients:  

mitoxantrone hydrochloride 2.328 mg, which corresponds to the content of mitoxantrone 2 mg.

Auxiliary substances:  

sodium chloride,

sodium acetate,

ice-cold acetic acid

, d/i water.

Pharmacological action

Pharmacodynamics

Oncotrone is a cytostatic drug, a synthetic derivative of anthracenedione. The mechanism of antitumor action is not fully elucidated, but preliminary data indicate that the drug, being embedded between the bases of the DNA molecule, blocks the processes of replication and transcription. In addition, mitoxantror inhibits topoisomerase II and has a non-specific effect on the cell cycle.

After intravenous use, mitoxantrone quickly penetrates and is distributed in the tissues, from where it is then gradually released. It is found in high concentrations in the liver, lungs, and in descending order: in the bone marrow, heart, thyroid, spleen, pancreas, adrenal glands, and kidneys. It does not penetrate the BBB.

Binding to plasma proteins is 90%. It is metabolized in the liver. Within 5 days,13.6-24.8% of the drug is excreted from the body with bile and from 5.2% to 7.9% with urine. Terminal T_1/2 reaches 9 days.

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

Indications

• Acute non-lymphoblastic leukemia in adults;
• breast cancer;
• malignant non-Hodgkin’s lymphoma;
• primary hepatic cell carcinoma;
• ovarian cancer;
• hormone-resistant prostate cancer with pain syndrome.

Use during pregnancy and lactation

It is contraindicated during pregnancy and lactation.

Contraindications

• Neutrophil count less than 1500 / µl (except for the treatment of non-lymphoblastic leukemia);
• lactation;
• pregnancy;
• hypersensitivity to mitoxantrone or any other components of the drug.

With caution: use Oncotrone in patients with heart disease, with previous mediastinal irradiation, with hematopoiesis suppression, with severe liver or kidney function disorders, with bronchial asthma, with acute infectious diseases of viral (including chickenpox, 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 with previously treated with anthracyclines.

Side effects

From the hematopoietic 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; rarely-increased activity of hepatic transaminases, impaired liver function.

From the cardiovascular system: ECG changes, tachycardia, arrhythmias, myocardial ischemia, decreased left ventricular ejection fraction, congestive heart failure. Toxic myocardial damage, in particular congestive heart failure, can develop both during treatment with mitoxantrone, and months or years after the end of therapy. The risk of cardiotoxic effects increases when a total dose of 140 mg/m2 is reached.

From the respiratory system: cases of interstitial pneumonitis have been described.

Allergic reactions: pruritus of the skin. rash, urticaria, shortness of breath, decreased blood pressure, anaphylactic reactions (including anaphylactic shock).

Local reactions: phlebitis, with estravasation-erythema, edema, pain, burning, necrosis of surrounding tissues. Cases of intense blue staining of the veins into which the drug was injected and the surrounding tissues are described.

Others: alopecia, fatigue, general weakness, fever, non-specific neurological symptoms, back pain, headache, menstrual disorders, amenorrhea; rarely-blue staining of the skin and nails; very rarely-nail dystrophy and reversible blue staining of the sclera, secondary infections, hyperuricemia, hypercreatininemia.

Interaction

Pharmaceutical interaction

Do not mix the drug with other drugs when administered intravenously (precipitation may occur).

Pharmacodynamic interaction

Oncotrone potentiates the action of many cytotoxic drugs, such as cytarabine, cisplatin, cyclophosphamide,5-fluorouracil, methotrexate, vincristine, dacarbazine.

Simultaneous use of Oncotrone with other antitumor agents or irradiation of the mediastinal region may increase its cardio – and myelotoxicity.

Concomitant use of drugs that block tubular secretion (including uricosuric anti-gout agents-sulfinpyrazone) may increase the risk of developing nephropathy.

Pharmacokinetic interaction

No dangerous interactions with other drugs were detected.

How to take, course of use and dosage

Mitoxantrone is part of many chemotherapeutic treatment regimens, and therefore, when choosing the route of use, regimen and doses in each individual case, you should be guided by the data of the specialized literature.

The drug is administered intravenously slowly, for at least 5 minutes, or intravenously drip for 15-30 minutes. It is preferable to introduce Oncotrone into the tube of the infusion system slowly against the background of rapid infusion with 0.9% sodium chloride solution or 5% glucose solution.

Intrathecal, intra-arterial, i / m, subcutaneous use of the drug is prohibited

The maximum total dose of Oncotrone is 200 mg/m2 of body surface.

In breast cancer, non-Hodgkin’s lymphoma, liver cancer and ovarian cancer in monotherapy, Oncotrone is used at a dose of 14 mg / m2 1 time in 3 weeks. In patients who have previously received chemotherapy, as well as in combination with other antitumor agents, the dose of the drug is reduced to 10-12 mg/m2. With repeated courses, the dose of Oncotrone is selected taking into account the severity and duration of inhibition of bone marrow hematopoiesis.

In the case of a decrease in the number of neutrophils with previous courses < 1500 and/or platelets 50,000 cells/µl of blood, the dose of Oncotrone is reduced 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 Oncotrone are reduced by 4 mg/m2.

In the treatment of acute non-lymphoblastic leukemia in adults, Oncotrone is prescribed to induce remission at a dose of 10-12 mg / m2 daily for 5 days up to a total dose of 50-60 mg/m2. It is possible to use high doses of Oncotrone 14 mg/m2 or more daily for 3 days.

For the treatment of hormone-resistant prostate cancer, Oncotrone is prescribed at a dose of 12-14 mg / m2 1 time in 21 days in combination with a daily intake of low doses of glucocorticosteroids (prednisone 10 mg / day or hydrocortisone 40 mg/day).

For intrapleural insertion, pleural metastases (breast cancer and non-Hodgkin’s lymphoma), the recommended single dose is 20-30 mg.

For intrapleural installation, Oncotrone is diluted in 50 ml of 0.9% sodium chloride solution. Before starting therapy, the pleural exudate is evacuated, as far as possible. Oncotrone, diluted in 50 ml of 0.9% sodium chloride solution, is warmed to body temperature and administered slowly for 5-10 minutes, without effort. The delay period of the first dose of Oncotrone in the pleural cavity is 48 h

. During this period, patients should move to ensure optimal intrapleural distribution of the drug. After the end of the specified time (48 hours), repeated drainage of the pleural cavity is performed. If the amount of effusion is less than 200 ml, then the 1st treatment cycle is stopped. If the amount of effusion exceeds 200 ml, a second installation of 30 mg of Oncotrone is prescribed. Before re-installing the drug, monitoring of hematological parameters is necessary. The 2nd dose of Oncotrone may remain in the pleural cavity.

The maximum dose for the 1st treatment cycle is 60 mg. If the number of neutrophils and platelets is within the normal range, intrapleural installation can be repeated after 4 weeks. Systemic cytostatic therapy should be avoided for 4 weeks before and 4 weeks after intrapleural use of Oncotrone.

Overdose

Symptoms: increased, first of all, myelotoxicity and the above-mentioned side effects.

Treatment: dialysis is not effective. In case of overdose, the patient should be carefully monitored and, if necessary, symptomatic therapy should be carried out. The specific antidote for mitoxantrone is unknown.

Special instructions

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

During treatment, it is necessary to systematically monitor the picture of peripheral blood (before each injection, a complete blood test is performed, including platelet counting), laboratory parameters of liver function, as well as heart activity (ECG, echocardiography with determination of the left ventricular ejection fraction (LVEF)). After reaching the total dose of mitoxantrone in 100 mg/m2, the determination of LVEF values should be carried out before each regular use of the drug.

Active or inactive cardiovascular diseases, mediastinal/pericardial radiation therapy performed earlier or simultaneously with mitoxantrone treatment, previous treatment with other anthracyclines or anthracenediones, and concomitant treatment with other cardiotoxic drugs may increase the risk of toxic heart damage. The risk of cardiotoxicity increases when the total dose of mitoxantrone exceeds 140 mg/m2, however, toxic heart damage can also develop at lower total doses of the drug.

Since some patients with acute leukemia may develop severe stomatitis, it is recommended to take preventive measures.

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

In case of extravasation, it is necessary to stop the drug use 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 may lead to the development of acute myeloblastic leukemia or myelodysplastic syndrome.

Due to the immunosuppressive effect of the drug and the possibility of developing severe infections, it is not recommended to use live vaccines during chemotherapy. Vaccination should be carried out 3 months after the end of therapy.

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

Avoid contact of the drug with the skin or mucous membranes, as tissue necrosis may occur. The skin, in case of contact with the drug, should be thoroughly rinsed with warm water.

If necessary, an undiluted solution of Oncotrone (with aseptic withdrawal of the drug from the bottle) can be used in parts for 7 days, provided that it is stored at a temperature not exceeding 25°C.

After dilution, the Oncotrone solution should be used for 4 days (aseptic sampling conditions, storage at a temperature of 4-25°C), after 96 hours, the unused drug should not be used.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

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

Form of production

Concentrate for solution preparation for intravenous and intrapleural use

Storage conditions

At a temperature not exceeding 25 °C (do not freeze)

Shelf life

3 years

Active ingredient

Mitoxantrone

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution