Doxorubicin Medak (doxorubicin) solution for infusions 2 mg/ml. 5 ml. (10 mg.) №1 vial

Description

Doxorubicin Medak solution Storage
active substance: 1 ml of solution contains 2 mg of doxorubicin hydrochloride;

Doxorubicin Medak solution Excipients:

sodium chloride, concentrated hydrochloric acid, water for injections.

Doxorubicin Medak solution Dosage form
Solution for infusion.

Main physical and chemical properties: clear red solution.

Pharmacotherapeutic group
Antineoplastic and immunomodulatory agents. Cytotoxic drugs (anthracyclines and related compounds). ATX code L01D B01.

Pharmacological properties

Pharmacodynamics.

Doxorubicin medak is an anthracycline antibiotic. It has an antitumor effect due to the cytotoxic mechanism of action, in particular by intercalation in DNA, inhibition of the enzyme topoisomerase II and the formation of reactive oxygen species (ROS). All this has a detrimental effect on DNA synthesis: intercalation of the doxorubicin molecule leads to inhibition of DNA and RNA polymerase synthesis due to violations in the basic recognition and sequence specificity. Inhibition of topoisomerase II leads to the rupture of single and double helices of DNA. Separation of DNA also occurs as a result of a chemical reaction with highly active forms of oxygen, such as, for example, a hydroxyl OH radical. The consequences of this are mutagenic and chromosomal abnormalities.

The specificity of doxorubicin toxicity is primarily related to the proliferative activity of healthy tissue. Thus, the bone marrow, gastrointestinal tract and gonads are the main healthy tissues that are damaged.

One of the main reasons for the ineffectiveness of treatment with doxorubicin and other anthracyclines is the development of resistance. Calcium antagonists such as verapamil are used to overcome cellular resistance to doxorubicin because the main target is the cell membrane. Verapamil blocks slow calcium channels and may increase cellular uptake of doxorubicin. In animal experiments, severe toxic effects were observed with the combined use of doxorubicin and verapamil.

Pharmacokinetics.

Following intravenous administration, rapid clearance of doxorubicin from blood plasma and its distribution to tissues including lung, liver, heart, spleen, lymph nodes, bone marrow and kidney is observed. Relatively low but stable levels are found in tumor tissue.

Doxorubicin is rapidly metabolized in the liver. The most common metabolite is doxorubicinol, although a significant number of patients develop doxorubicin-7-dioxyaglycone and doxorubicinol-7-dioxiaglycone. About 40-50% of the dose is excreted in bile within 7 days, of which almost half is excreted as unchanged active substance. Approximately 5% of the dose is excreted in the urine within 5 days. Doxorubicinol, the main (active) metabolite, is excreted in both bile and urine. Doxorubicinol does not cross the blood-brain barrier, but crosses the placenta and is excreted in breast milk. Plasma excretion of doxorubicin is three-phase with half-lives of 12 minutes, 3.3 hours and 30 hours.

Volume of distribution – 25 l; the degree of binding of doxorubicin to plasma proteins is 60-70%. There are significant interpersonal differences in the biotransformation of doxorubicin. Clearance is clearly not dose-dependent, but it is greater in men than in women.

When liver function is impaired, the excretion of doxorubicin slows down and, as a consequence, increases its delay and accumulation in plasma and tissues. In such cases, dose reduction is recommended, although there is no clear relationship between liver function tests, doxorubicin clearance and clinical toxicity. Because doxorubicin and its metabolites are only slightly excreted in the urine, there is no clear evidence that the pharmacokinetic parameters or toxicity of doxorubicin are altered in patients with renal impairment.

Although renal excretion is a minor route of excretion of doxorubicin, severe renal insufficiency may affect overall elimination and require dose reduction.

In studies involving overweight patients (> 130% of ideal body weight), doxorubicin clearance decreased and the half-life increased compared to the corresponding values ​​in the control group of patients with normal body weight. Therefore, overweight patients require dose adjustment.

Indication
Doxorubicin medak is a cytotoxic drug indicated for the following non-plastic diseases:

small cell lung cancer;
breast cancer;
recurrent ovarian cancer;
systemic therapy of locally advanced or metastatic bladder cancer;
intravesical prevention of disease recurrence in superficial bladder cancer after transurethral resection;
adjuvant and neoadjuvant therapy for osteosarcoma;
common forms of soft tissue sarcoma in adults;
Ewing’s sarcoma;
Hodgkin’s lymphoma;
non-Hodgkin’s lymphoma;
acute lymphoblastic leukemia;
acute myeloblastic leukemia;
widespread multiple myeloma;
late stage or recurrence of endometrial carcinoma;
Williams tumor;

Contraindication
Hypersensitivity to the active substance or to any of the excipients. Pregnancy and breastfeeding.

Contraindications for intravenous administration:

persistent myelosuppression or severe stomatitis caused by previous cytotoxic treatment and / or radiation;
systemic infections;
severe liver dysfunction;
severe arrhythmia, heart failure, recent myocardial infarction, acute inflammatory heart disease;
previous treatment with maximum cumulative doses of anthracyclines;
increased tendency to bleed.
Contraindications for intravesical administration:

invasive tumors that grow in the bladder;
urinary tract infections;
inflammation of the bladder;
catheterization problems, such as urethral stenosis;
hematuria.
The drug should be discontinued in the presence or development of bone marrow depression or ulcers in the mouth. The latter may be preceded by such precursor symptoms as a burning sensation in the mouth. In the presence of this symptom to continue the drug is not recommended.