Oncotron, 2 mg/ml 10 ml

Pharmacodynamics

Oncotron is a cytostatic drug, a synthetic derivative of anthracenedione. The mechanism of antitumor action is not fully understood, but preliminary data shows that the drug, being inserted between the bases of DNA molecule, blocks the processes of replication and transcription. In addition, mitoxanthror inhibits topoisomerase II and has a nonspecific effect on the cell cycle.

Pharmacokinetics

Mitoxantrone quickly penetrates and distributes into tissues after IV administration, from where it is then gradually released. It is found in high concentrations in the liver, lungs and in descending order: bone marrow, heart, thyroid, spleen, pancreas, adrenal glands and kidneys. It does not penetrate the GEB.

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

In patients with hepatic dysfunction, a decrease in the elimination rate of the drug has been noted.

Indications

Active ingredient

Composition

1 ml of the concentrate contains:

The active ingredients:

Mitoxantrone hydrochloride 2.328 mg, corresponding to a mitoxantrone content of 2 mg.

Auxiliary substances:

Sodium chloride,

Sodium acetate,

Led acetic acid,

water d/i.

How to take, the dosage

Mitoxantrone is part of many chemotherapeutic treatment regimens, therefore, when choosing the route of administration, regimen and doses in each individual case, the data of the special literature should be followed.

The drug is administered by IV slowly for at least 5 minutes or by IV drip for 15-30 minutes. It is preferable to inject Oncotron into a tube infusion system slowly against the background of rapid infusion with 0.9% sodium chloride solution or 5% glucose solution.

Intrathecal, intra-arterial, intramural, intramural, p/u administration of the drug is prohibited

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

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

In case of decreased neutrophil counts in previous courses of < 1500 and/or platelet counts of 50,000 cells/μl of blood, the Oncotron dose is reduced by 2 mg/msup>2 when neutrophil count < 1,000 and/or platelet count < 25,000 cells/µl of blood is decreased, subsequent doses of Oncotron are reduced by 4 mg/m2.

In the treatment of acute non-lymphoblastic leukemia in adults, Oncotron is administered at a dose of 10-12 mg/m2 daily for 5 days to a total dose of 50-60 mg/m2 to induce remission. High doses of Oncotron 14 mg/m2 or more daily for 3 days may be used.

To treat hormone-resistant prostate cancer, Oncotron is prescribed at a dose of 12-14 mg/m2 once every 21 days in combination with daily low-dose glucocorticosteroids (prednisolone) 10 mg/day or hydrocortisone 40 mg/day).

In intrapleural instillation, for metastases to the pleura (in breast cancer and non-Hodgkin’s lymphoma), the recommended single dose is 20-30 mg.

For intrapleural injection Oncotron is diluted in 50 ml of 0.9% sodium chloride solution. Evacuate pleural exudate, if possible, before starting therapy. Oncotron diluted in 50 ml of 0.9% sodium chloride solution is warmed to body temperature and injected slowly for 5-10 min, without applying force. The retention period of the first dose of Oncotron in the pleural cavity is 48 hours. H

Patients should move during this period to ensure optimal intrapleural distribution of the drug. After the specified time (48 h) the pleural cavity is drained again. If the amount of effusion is less than 200 ml, the 1st cycle of treatment is stopped. If the amount of effusion exceeds 200 ml, a repeated instillation of 30 mg Oncotron is prescribed. Hematological parameters should be checked before repeated instillation of the drug. The 2nd dose of Oncotron may remain in the pleural cavity.

The maximum dose for the 1st cycle of treatment is 60 mg. If neutrophil and platelet counts are within normal limits, the intrapleural instillation may be repeated after 4 weeks. Systemic therapy with cytostatic agents should be avoided for 4 weeks before and 4 weeks after intrapleural injection of Oncotron.

Interaction

Pharmaceutical Interactions

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

Pharmacodynamic interaction

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

The concomitant use of Oncotron with other anticancer drugs or mediastinal irradiation may increase its cardio- and myelotoxicity.

The concomitant use of agents that block tubular secretion (including uricosuric antipodagric agents – sulfinpyrazone) may increase the risk of nephropathy.

Pharmacokinetic interactions

No dangerous interactions with other medicinal products have been found.

Special Instructions

The treatment with Mitoxantrone should be done under the supervision of a physician experienced in the use of antitumor drugs.

The treatment requires systematic monitoring of the peripheral blood picture (a complete blood count, including platelet count, is mandatory before each administration), laboratory parameters of liver function, and cardiac activity (ECG, EchoCG with determination of left ventricular ejection fraction (LVEF)). After a total dose of mitoxantrone of 100 mg/m2 has been reached, determination of RVEF values should always be performed before each subsequent drug administration.

Cardiovascular disease in the active or inactive phase, radiation therapy to the mediastinal/pericardial area, previous or concomitant treatment with mitoxantrone, prior treatment with other anthracyclines or anthracenedione, and concomitant treatment with other cardiotoxic agents may increase the risk of toxic cardiac damage. The risk of cardiotoxicity is increased when the total dose of mitoxantrone exceeds 140 mg/m2; however, toxic cardiac damage can also develop at lower total doses of the drug.

Because severe stomatitis may develop in some patients with acute leukemia, prophylactic measures are recommended.

Hyperuricemia may occur during treatment of leukemia as a result of rapid decay of tumor cells. Hypouricemic drugs should be prescribed if necessary.

In case of extravasation, the drug administration should be stopped and, if necessary, the infusion should be continued in another vein.

The use of topoisomerase II inhibitors, including mitoxantrone, in combination with other anticancer drugs and/or radiotherapy may lead to acute myeloblastic leukemia or myelodysplastic syndrome.

Because of the immunosuppressive effect of the drug and the possibility of severe infections, live vaccines are not recommended during chemotherapy. Vaccination should be done 3 months after completion of therapy.

Women and men should use reliable contraceptive methods during treatment with mitoxantrone and for 6 months after withdrawal.

Contact of the drug with the skin or mucous membranes should be avoided because tissue necrosis may occur. The skin, if in contact with the drug, should be rinsed thoroughly with warm water.

If necessary, the undiluted Oncotron solution (with aseptic withdrawal of the drug from the vial) can be used in portions over 7 days provided that it is stored at a temperature not exceeding 25°C.

After dilution, Oncotron solution should be used within 4 days (aseptic withdrawal conditions, storage at 4-25°C), after 96 h the unused drug should not be used.

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

At the time of treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

With caution: use Oncotron in patients with heart disease, with prior mediastinal irradiation, with suppression of hematopoiesis, with significant liver or renal dysfunction, with bronchial asthma, with acute infectious diseases of viral (including varicella pox), with acute viral diseases.

In patients with acute infectious diseases of viral (including varicella, shingles), fungal or bacterial nature (risk of severe complications and generalization), diseases with increased risk of hyperuricaemia (gout or urate nephrolithiasis) and patients previously treated with anthracyclines.

Side effects

Blood system: leukopenia (usually on day 6-15, recovery on day 21), neutropenia. thrombocytopenia, erythrocytopenia; rarely – anemia.

In the digestive system: nausea, vomiting, anorexia, decreased appetite, diarrhea, abdominal pain, constipation, gastrointestinal bleeding, stomatitis; rarely – increased liver transaminases activity, liver function impairment.

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

Respiratory system: cases of interstitial pneumonitis have been described.

Allergic reactions: skin itching. rash, urticaria, dyspnea, decreased BP, anaphylactic reactions (including anaphylactic shock).

Local reactions: phlebitis, in estravation – erythema, edema, pain, burning, necrosis of the surrounding tissues. Cases of intense blue staining of the veins into which the drug was injected and the surrounding tissues have been described.

Others: alopecia, increased fatigue, general weakness, increased body temperature, nonspecific neurological symptoms, back pain, headache, menstrual cycle disorders, amenorrhea; rarely – blue staining of skin and nails; very rarely – nail dystrophy and reversible blue staining of sclerae, secondary infections, hyperuricemia, hypercreatininemia.

Overdose

Symptoms: aggravation, primarily myelotoxicity and the above mentioned side effects.

Treatment: the use of dialysis is not effective. In case of overdose, the patient should be closely monitored and, if necessary, symptomatic therapy should be administered. A specific antidote for mitoxantrone is not known.

Pregnancy use

It is contraindicated during pregnancy and lactation.