Doxorubicin lyophilisate for preparation of the solution vial 10mg

Mechanism of action

Antitumor agent from the group of anthracycline antibiotics. The mechanism of action is DNA binding and inhibition of nucleic acid synthesis.

The volume of distribution in the equilibrium state is 20-30 l / kg. Does not penetrate the BBB. Biotransformation occurs in the liver to form an active metabolite. The half-life for doxorubicin and doxirubicinol varies from 20 to 48 hours. It is excreted in the bile unchanged (about 40% within 5 days) and the kidneys unchanged and as metabolites (about 5-12% within 5 days).

Indications and usage

Lymphoblastic leukemia, soft tissue sarcoma, osteogenic sarcoma, Ewing's sarcoma, breast cancer, thyroid cancer, Wilms tumor, neuroblastoma, bladder cancer, stomach cancer, ovarian cancer, lymphogranulomatosis, non-Hodgkin's lymphomas, trophoblastic tumors.

The dosage regimen is set individually, depending on the evidence, the patient's condition and the cytotoxic therapy regimen used. Enter only in / in, 60-75 mg / m² 1 time in 3-4 weeks, or 20-30 mg / m² for 3 days every 3-4 weeks, or 30 mg / m² Once a week for 3-4 weeks. The break between courses is 3-4 weeks.
Maximum total dose doxorubicin is 550 mg / m².
When applying doxorubicin in patients with impaired liver function, it should be borne in mind that if the level of bilirubin is increased by 2-3 times, then the dose of doxorubicin is reduced by 50-75%, respectively.

Adverse reactions

Hemic and lymphatic: thrombocytopenia, leukopenia, anemia.
Cardiovascular: cardiomyopathy, heart failure, arrhythmias.
Gastrointestinal: stomatitis, esophagitis, abdominal pain; nausea, vomiting, diarrhea.
From the reproductive system: azoospermia, amenorrhea.
Allergic reactions: urticaria, fever, anaphylactoid reactions.
Other: alopecia, hyperuricemia, nephropathy.
Local reactions: with the introduction into the veins of small diameter or with the re-introduction into the same vein - hardening of the vessel; with extravasation - tissue necrosis.

Contraindications

Severe leukopenia, anemia, thrombocytopenia; severe diseases of the cardiovascular system; acute hepatitis; pregnancy. Doxorubicin is not used in patients who receive a full cumulative dose of daunorubicin, idarubicin and / or other anthracyclines and anthracene.

Pregnancy and breastfeeding

Doxorubicin is contraindicated for use in pregnancy. If necessary, use during lactation should stop breastfeeding.
Women of childbearing age should use reliable contraceptive methods when using doxorubicin.
AT experimental studies The teratogenic and embryotoxic effects of doxorubicin have been established.

With care prescribed to patients with heart disease (including in history), chickenpox (including recently suffered or after contact with the sick), herpes zoster, other acute infectious diseases, gout or nephrolithiasis (including in history), as well as in patients with mediastinal radiation therapy or cyclophosphamide.
During the period of treatment, regular monitoring of the picture of peripheral blood, laboratory parameters of liver function, ECG and ultrasound of the heart (with the definition of the left ventricular ejection fraction) is necessary. When the number of leukocytes is less than 3300-3500 / mm³ and platelet count less than 100,000 / mm³ doxorubicin dose is reduced by 50%.
Cases of the development of severe, life-threatening arrhythmias immediately or within a few hours after the administration of doxorubicin are described.
Do not recommend vaccinating patients and their families.
Doxorubicin may cause urine to stain red for 1–2 days after administration.
AT experimental studies The carcinogenic and mutagenic effects of doxorubicin have been established.
Doxorubicin in powder form for injection and solution for injection is included in the VED list.

Drug Interactions

When combined, doxorubicin can potentiate the hepatotoxic effect of 6-mercaptopurine.
When using doxorubicin (IV for 3 days) in combination with cytarabine (as an infusion for 7 days), cases of necrotic colitis and severe infectious complications are described.
With simultaneous use with cyclosporine, cases of coma and / or seizures are described.
With simultaneous use with cyclophosphamide, mitomycin may enhance cardiotoxic action.
When combined with the use of uricosuric drugs increases the risk of nephropathy.
With simultaneous use with streptozocin may increase the half-life of doxorubicin.