Rubomycin (Lyophilisate) Instructions for Use

ATC Code

L01DB02 (Daunorubicin)

Active Substance

Daunorubicin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antineoplastic antibiotic

Pharmacotherapeutic Group

Antineoplastic agent, antibiotic

Pharmacological Action

An antineoplastic agent from the group of anthracycline antibiotics, produced by Streptomyces coeruleorubidis. The cytotoxic action is due to its ability to inhibit the synthesis of DNA, RNA, and proteins.

The mechanism of action is based on the intercalation of the anthracycline between adjacent base pairs of the DNA double helix, which prevents its “unwinding” for subsequent replication.

Pharmacokinetics

After intravenous administration, it is rapidly distributed in the body, especially in the kidneys, spleen, liver, and heart. It does not penetrate the blood-brain barrier.

It is metabolized in the liver to form the active metabolite daunorubicinol.

The half-life (T_1/2) in the initial phase is 45 minutes; in the terminal phase – for daunorubicin it is 18.5 hours, for daunorubicinol 26.7 hours, and for other metabolites 55 hours. It is excreted by the kidneys and with bile.

Indications

Acute leukemia, lymphogranulomatosis (Hodgkin’s disease), uterine chorioepithelioma, neuroblastoma, Ewing’s sarcoma, Wilms’ tumor, non-Hodgkin lymphomas.

ICD codes

Dosage Regimen

Determine the dosage individually based on the specific disease, its stage, the patient’s hematological status, and the chosen antineoplastic therapy regimen.

Administer the lyophilisate intravenously only. Do not administer intramuscularly or subcutaneously.

Reconstitute the lyophilisate immediately before use with the provided solvent to achieve the required concentration.

For acute non-lymphoblastic leukemia in adults, use a dose of 30-60 mg/m² of body surface area daily for 3 consecutive days. Repeat the cycle every 3-4 weeks.

For acute lymphoblastic leukemia in adults, use a dose of 30-45 mg/m² daily for 3 days in combination with other cytostatics.

For pediatric patients, calculate the dose based on body surface area. The total cumulative dose in children must not exceed 300 mg/m² to minimize the risk of cardiotoxicity.

In adults, strictly monitor the total cumulative dose. Do not exceed a cumulative dose of 400-550 mg/m².

Reduce the dosage in patients with impaired hepatic function or renal function. Do not use in cases of severe hepatic or renal impairment.

Assess the patient’s complete blood count, cardiac function via ECG and echocardiography, and hepatic and renal function before initiating therapy and before each subsequent cycle.

Discontinue treatment immediately if signs of cardiotoxicity appear.

Adverse Reactions

From the hematopoietic system: anemia, leukopenia, thrombocytopenia.

From the digestive system: nausea, vomiting, diarrhea, stomatitis.

From the cardiovascular system: heart failure, arrhythmias; rarely – myocarditis, pericarditis.

From the reproductive system: amenorrhea, azoospermia.

Other: alopecia, allergic reactions, headache.

Local reactions: pain at the injection site, tissue necrosis (if the injection technique is violated).

Contraindications

Leukopenia (white blood cell count below 4000/µL), thrombocytopenia (platelet count below 120,000/µL), chronic heart failure in the stage of decompensation, severe impairment of liver and/or kidney function, peptic ulcer of the stomach and duodenum in the acute phase, pregnancy, hypersensitivity to daunorubicin.

Use in Pregnancy and Lactation

Daunorubicin is contraindicated during pregnancy. If it is necessary to use it during lactation, breastfeeding should be discontinued.

Women of childbearing potential should use reliable methods of contraception during therapy with daunorubicin.

In experimental studies, the teratogenic and embryotoxic effects of daunorubicin have been established.

Use in Hepatic Impairment

Contraindicated in severe liver function impairment. Use with caution in patients with impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal function impairment. Use with caution in patients with impaired kidney function.

Pediatric Use

The frequency of cardiotoxic side effects in children increases if the total cumulative dose of daunorubicin exceeds 300 mg/m².

Impairments of myocardial contractility, symptoms of chronic heart failure, and other cardiotoxic effects of daunorubicin in children may appear several months or even years after the end of treatment, therefore, monitoring of the functional state of the cardiovascular system should be carried out for a long time.

Special Precautions

Use with caution in patients with impaired renal and/or liver function, with heart disease (including in the anamnesis), gout or nephrolithiasis (including in the anamnesis), as well as in patients who have received or are currently receiving combined chemotherapy with other antineoplastic drugs that have a myelotoxic effect, or a course of radiation therapy.

The use of daunorubicin is not recommended in patients with chickenpox (including those who have recently had it or after contact with sick people), with herpes zoster, or other acute infectious diseases.

Before starting and during treatment, monitoring of the peripheral blood count, functional state of the kidneys, liver, chest X-ray, ECG, echocardiography, and determination of cardiac stroke volume are necessary.

The frequency of cardiotoxic side effects increases if the total cumulative dose of daunorubicin exceeds 400 mg/m² in adults and 300 mg/m² in children.

Impairments of myocardial contractility, symptoms of chronic heart failure, and other cardiotoxic effects of daunorubicin may appear several months or even years after the end of treatment (especially in children), therefore, monitoring of the functional state of the cardiovascular system should be carried out for a long time.

Vaccination of the patient or family members is not recommended.

It is not recommended to use Daunorubicin in patients who have previously received full cumulative doses of doxorubicin. If the received course dose of doxorubicin is below the cumulative dose, then the total dose of daunorubicin and doxorubicin should not exceed 550 mg/m².

In the first few days of using daunorubicin, urine may turn red.

Drug Interactions

With simultaneous use with drugs that have a myelotoxic effect, an increase in toxic effects is possible.

When used with cyclophosphamide or doxorubicin, the risk of cardiotoxicity increases.

With combined use with methotrexate (or with other drugs with hepatotoxic action), the likelihood of hepatotoxicity increases.

The use of daunorubicin with uricosuric drugs increases the risk of nephropathy.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.