Doxorubicin hydrochloride

metastatic breast cancer in the presence of indications for anthracycline therapy, including in the case of an increased risk of cardiac complications and in the case of ineffective therapy with taxanes,

common ovarian cancer with ineffective platinum-based chemotherapy,

progressive multiple myeloma (in combination with bortezomib) in patients who have received at least one line of chemotherapy and have undergone a bone marrow transplant (TCM) or are not candidates for TCM,

AIDS-associated Kaposi's sarcoma in patients with low CD4 levels (<200 CD4 lymphocytes / mm³) and extensive lesions of the skin and mucous membranes or visceral organs, other than Kaposi's sarcoma, amenable to local treatment or systemic treatment with interferon alpha. The drug Kelix^® It can be used as a 1st or 2nd line of chemotherapy in patients with AIDS-associated Kaposi's sarcoma who are insensitive to drugs such as periwinkle alkaloids, bleomycin, and standard doxorubicin (or other anthracyclines).

metastatic breast cancer in the presence of indications for anthracycline therapy, including in the case of an increased risk of cardiac complications and in the case of ineffective therapy with taxanes,

common ovarian cancer with ineffective platinum-based chemotherapy,

progressive multiple myeloma (in combination with bortezomib) in patients who have received at least one line of chemotherapy and have undergone a bone marrow transplant (TCM) or are not candidates for TCM,

AIDS-associated Kaposi's sarcoma in patients with low CD4 levels (<200 CD4 lymphocytes / mm³) and extensive lesions of the skin and mucous membranes or visceral organs, other than Kaposi's sarcoma, amenable to local treatment or systemic treatment with interferon alpha. Doxorubicin hydrochloride^® It can be used as a 1st or 2nd line of chemotherapy in patients with AIDS-associated Kaposi's sarcoma who are insensitive to drugs such as periwinkle alkaloids, bleomycin, and standard doxorubicin (or other anthracyclines).

Breast, thyroid, lung, bladder (including superficial tumors), ovarian, osteosarcoma, soft tissue sarcoma, lymphogranulomatosis, non-Hodgkin's lymphoma, neuroblastoma, Wilms tumor, acute lymphoblastic leukemia, acute myeloblastic leukemia.

Breast and thyroid cancer, soft tissue sarcoma, osteogenic sarcoma, lymphosarcoma, acute leukemia, cervical and endometrial cancer, testicular cancer, prostate cancer, head and neck cancer, lung cancer, bladder cancer, myeloma, Hodgkin's disease and non-Hodgkin's lymphoma, neuroblastoma.

In/in, for 2-3 minutes (pre-dissolve the contents of the bottle with 10 mg of the drug in 5 ml of isotonic sodium chloride solution, 50 mg - in 25 ml). Most often-60-75 mg / m² 1 time in 3 weeks or 20 mg / m² weekly or 20-30 mg / m² daily (3 days), with a repeat of the course every 3-4 weeks. At a bilirubin level of 12-30 mg / l, the dose should be reduced by 50%, at a level of more than 30 mg/l — by 75%. Total dose-no more than 550 mg / m², in patients who underwent radiation therapy on the chest area or were treated with cardiotoxic drugs-no more than 400 mg/m².

Intravesical-30-50 mg for instillation at intervals of 1 week to 1 month (the recommended concentration of the solution is 1 mg / ml of water for injection).

In / in drip. The drug can not be administered in a jet or undiluted form.

Treatment is continued until signs of progression or development of unacceptable toxicity appear.

The drug Kelix^® It has unique pharmacokinetic properties and should not be replaced by other forms of doxorubicin hydrochloride. Treatment with Kelix^® it should be carried out only under the supervision of a qualified oncologist who has experience in cytostatic therapy.

Breast cancer and ovarian cancer

In breast cancer and ovarian cancer, the drug is administered at a dose of 50 mg / m² 1 time in 4 weeks, until the progression of the disease and while the permissible tolerance is maintained.

At a calculated dose of less than 90 mg, the concentrate is diluted in 250 ml of 5% dextrose solution for infusions, at a dose of 90 mg or more - in 500 ml of 5% dextrose solution for infusions. To reduce the risk of developing infusion reactions, the first administration is carried out at a rate of no more than 1 mg / min. In the absence of reactions, subsequent infusions can be carried out within 60 minutes.

Repeated administration of the drug to patients who had infusion reactions to the previous administration should be carried out as follows: 5%of the calculated dose is administered slowly for 15 minutes. In the absence of reactions, the administration is continued at twice the speed for another 15 minutes. With good tolerability, the infusion is continued for the next hour (the total time of administration is 90 minutes). Subsequent infusions of the drug Kelix^® can be held for 60 minutes.

Multiple myeloma

In the treatment of multiple myeloma Kelix^® enter in a dose of 30 mg/m² on the 4th day of the three-week cycle in combination with bortezomib (1.3 mg / m² on days 1, 4, 8, and 11). Kelix^® it is administered immediately after bortezomib for 1 hour. The therapy is indicated as long as the effect of the treatment is observed with its acceptable tolerability.

At a calculated dose of less than 90 mg, the concentrate is diluted in 250 ml of 5% (50 mg/ml) dextrose solution for infusions, at a dose of 90 mg or more — in 500 ml of 5% (50 mg/ml) dextrose solution for infusions.

The intravenous catheter and drip system should be flushed with a 5% dextrose solution between the administration of bortezomib and doxorubicin. If it is impossible to administer Kelix and bortezomib on the 4th day of the cycle, their administration can be postponed for 48 hours. If the administration of bortezomib was made later than the time indicated by the therapy scheme, then the subsequent administration of bortezomib should be carried out no earlier than 72 hours after the last dose. The first infusion of the drug Kelix^® it can be assigned within 90 minutes according to the scheme:

- 10 ml first 10 min,

- 20 ml for the next 10 minutes,

- 40 ml for the next 10 minutes,

- then the remaining amount of the solution for 60 minutes.

In the subsequent dose of the drug Kelix^® it can be administered within 1 hour If there is an occurrence of reactions to the infusion of the drug Kelix^®, the infusion is stopped and after the symptoms disappear, the drug Kelix is prescribed^® according to the following scheme:

- 10 ml for the first 10 minutes,

- 20 ml for the next 10 minutes,

- 40 ml for the next 10 minutes,

- then the remaining amount of solution for 60 minutes.

The infusion can be performed through a central or peripheral venous catheter.

Kaposi's AIDS-associated sarcoma

The drug is administered intravenously at a dose of 20 mg / m² 1 time every 2-3 weeks, until the disease progresses and while the permissible tolerance is maintained. Intervals between dosing of less than 10 days should be avoided, since in this case, the drug may accumulate in the body and increase its toxicity. To achieve a therapeutic effect, the course of treatment should be 2-3 months. Treatment should be continued to maintain the therapeutic effect.

The concentrate is diluted in 250 ml of 5% dextrose solution for infusions and administered as intravenous infusions for 30 minutes.

General rules for all patients. If the patient has initial symptoms or signs of a reaction to the administration of the drug, the infusion is immediately stopped, premedicated with antihistamines and / or fast-acting corticosteroids, and the infusion is resumed at a slower rate. Do not administer the drug in the form of bolus injections or in the form of an undiluted solution. When performing infusions, it is recommended to combine the solution of the drug Kelix^® through the extreme port of intravenous infusion with an aqueous solution of 5% dextrose to achieve further dissolution and reduce the risk of thrombosis and bruising. The infusion can be carried out through the peripheral vein.

The drug Kelix^® it should not be administered in / m or n / a, you can not use infusion systems with built-in filters.

To reduce the manifestations of certain side effects, such as palmar-plantar syndrome (erythrodysesthesia), stomatitis or hematological toxicity, the dose of the drug can be reduced or canceled.

Modification of the dosage regimen

Instructions for changing the dosage regimen of the drug Kelix^® they are shown in the tables. The degrees of toxicity shown in the tables are based on the toxicity scale National Cancer Institute (NCI-CTC).

Table 1

Modification of the dosage regimen in connection with the development of palmar-plantar syndrome and stomatitis

Table 2

Modification of the dosage regimen due to the development of hematological toxicity (in breast cancer, ovarian cancer)

Table 3

Modification of the dosage regimen for multiple myeloma

*For more information about the bortezomib regimen and dose adjustment, see the bortezomib instructions for use ("Dosage and administration").

If a patient with multiple myeloma receiving combination therapy with Kelix^® and bortezomib, develops palmar-plantar syndrome or stomatitis, then the dose of the drug Kelix^® it should be adjusted as indicated in table 1.

Patients with impaired liver function. When the serum bilirubin content is from 1.2 to 3 mg/dl, the calculated dose is reduced by 25%. If the bilirubin content exceeds 3 mg/dl, the calculated dose is reduced by 50%. If the patient has well tolerated the administration of this dose (without hyperbilirubinemia or increased activity of liver enzymes in the blood serum), then the next dose is increased to the previous level (i.e., if the dose is reduced by 25% , it is increased to the full dose, if the dose is reduced by 50%, it is increased to 75% of the full dose). With good tolerability in subsequent cycles, the dose can be increased to the full dose. Kelix^® it can be prescribed to patients with liver metastases with concomitant hyperbilirubinemia and increased activity of liver enzymes, up to 4 times higher than the ULN. Before administration of the drug Kelix^® It is necessary to conduct a clinical and laboratory study of liver function, including the determination of the activity of ALT/AST, alkaline phosphatase, and bilirubin.

Patients with impaired renal function. Correction of the dosage regimen is not required. There are no data on the pharmacokinetics of the drug in patients with a creatinine Cl of less than 30 ml/min.

Patients with AIDS-associated Kaposi's sarcoma and splenectomy. Since at the moment there is no clinical data on the use of the drug Akelix^® for the treatment of this group of patients, the use of the drug Kelix^® in these patients, it is not recommended.

Children. Limited safety data obtained in Phase I studies indicate that doses up to 60 mg / m every 4 weeks are well tolerated in pediatric practice, however, the effectiveness of the drug Kelix^® for the treatment of patients under 18 years of age is not established.

Adult patients. In patients aged 21 to 75 years, there are significant differences in the pharmacokinetics of the drug Kelix^® not detected.

Rules for the preparation and administration of solution for infusions

Do not use the drug with signs of precipitation or the presence of suspended particles.

When using the drug, it is necessary to follow the rules for working with antitumor drugs. It is necessary to use gloves. In case of ingestion of the drug Kelix^® on the skin or mucous membranes, immediately wash this area with soap and water.

Determine the dose of the drug Kelix^®, required for the introduction. The required volume of the drug is collected in a sterile syringe. All manipulations should be carried out with strict compliance with the rules of asepsis (the drug does not contain preservatives and bacteriostatic additives).

It is recommended to enter Kelix^® through the side port of the infusion system, through which a 5% dextrose solution is injected to achieve greater dilution and minimize the risk of thrombosis and extravasation. The infusion can be carried out in the peripheral vein.

Kelix^® you can not enter in / m or p / K.

Do not use for the administration of the drug Kelix^® infusion systems with a built-in filter.

It is recommended to enter Kelix^® immediately after dilution with 5% dextrose solution for infusions. In cases where this is not possible, the prepared solution can be stored at a temperature of 2-8 °C and used for 24 hours.

In / in drip. The drug can not be administered in a jet or undiluted form.

Treatment is continued until signs of progression or development of unacceptable toxicity appear.

Doxorubicin hydrochloride^® It has unique pharmacokinetic properties and should not be replaced by other forms of doxorubicin hydrochloride. Treatment with Doxorubicin hydrochloride^® it should be carried out only under the supervision of a qualified oncologist who has experience in cytostatic therapy.

Breast cancer and ovarian cancer

In breast cancer and ovarian cancer, the drug is administered at a dose of 50 mg / m² 1 time in 4 weeks, until the progression of the disease and while the permissible tolerance is maintained.

At a calculated dose of less than 90 mg, the concentrate is diluted in 250 ml of 5% dextrose solution for infusions, at a dose of 90 mg or more - in 500 ml of 5% dextrose solution for infusions. To reduce the risk of developing infusion reactions, the first administration is carried out at a rate of no more than 1 mg / min. In the absence of reactions, subsequent infusions can be carried out within 60 minutes.

Repeated administration of the drug to patients who had infusion reactions to the previous administration should be carried out as follows: 5%of the calculated dose is administered slowly for 15 minutes. In the absence of reactions, the administration is continued at twice the speed for another 15 minutes. With good tolerability, the infusion is continued for the next hour (the total time of administration is 90 minutes). Subsequent infusions of Doxorubicin hydrochloride^® can be held for 60 minutes.

Multiple myeloma

In the treatment of multiple myeloma Doxorubicin hydrochloride^® enter in a dose of 30 mg/m² on the 4th day of the three-week cycle in combination with bortezomib (1.3 mg / m² on days 1, 4, 8, and 11). Doxorubicin hydrochloride^® it is administered immediately after bortezomib for 1 hour. The therapy is indicated as long as the effect of the treatment is observed with its acceptable tolerability.

At a calculated dose of less than 90 mg, the concentrate is diluted in 250 ml of 5% (50 mg/ml) dextrose solution for infusions, at a dose of 90 mg or more — in 500 ml of 5% (50 mg/ml) dextrose solution for infusions.

The intravenous catheter and drip system should be flushed with a 5% dextrose solution between the administration of bortezomib and doxorubicin. If it is impossible to administer Doxorubicin hydrochloride and bortezomib on the 4th day of the cycle, their administration can be postponed for 48 hours. If the administration of bortezomib was made later than the time indicated by the therapy scheme, then the subsequent administration of bortezomib should be carried out no earlier than 72 hours after the last dose. First infusion of Doxorubicin hydrochloride^® it can be assigned within 90 minutes according to the scheme:

- 10 ml first 10 min,

- 20 ml for the next 10 minutes,

- 40 ml for the next 10 minutes,

- then the remaining amount of the solution for 60 minutes.

Subsequently, the dose of the drug Doxorubicin hydrochloride^® it can be administered within 1 hour If there are reactions to the infusion with Doxorubicin hydrochloride^®, the infusion is stopped and after the symptoms disappear, the drug Doxorubicin hydrochloride is prescribed^® according to the following scheme:

- 10 ml for the first 10 minutes,

- 20 ml for the next 10 minutes,

- 40 ml for the next 10 minutes,

- then the remaining amount of solution for 60 minutes.

The infusion can be performed through a central or peripheral venous catheter.

Kaposi's AIDS-associated sarcoma

The drug is administered intravenously at a dose of 20 mg / m² 1 time every 2-3 weeks, until the disease progresses and while the permissible tolerance is maintained. Intervals between dosing of less than 10 days should be avoided, since in this case, the drug may accumulate in the body and increase its toxicity. To achieve a therapeutic effect, the course of treatment should be 2-3 months. Treatment should be continued to maintain the therapeutic effect.

The concentrate is diluted in 250 ml of 5% dextrose solution for infusions and administered as intravenous infusions for 30 minutes.

General rules for all patients. If the patient has initial symptoms or signs of a reaction to the administration of the drug, the infusion is immediately stopped, premedicated with antihistamines and / or fast-acting corticosteroids, and the infusion is resumed at a slower rate. Do not administer the drug in the form of bolus injections or in the form of an undiluted solution. When performing infusions, it is recommended to combine the solution of the drug Doxorubicin hydrochloride^® through the extreme port of intravenous infusion with an aqueous solution of 5% dextrose to achieve further dissolution and reduce the risk of thrombosis and bruising. The infusion can be carried out through the peripheral vein.

Doxorubicin hydrochloride^® it should not be administered in / m or n / a, you can not use infusion systems with built-in filters.

To reduce the manifestations of certain side effects, such as palmar-plantar syndrome (erythrodysesthesia), stomatitis or hematological toxicity, the dose of the drug can be reduced or canceled.

Modification of the dosage regimen

Instructions for changing the dosage regimen of Doxorubicin hydrochloride^® they are shown in the tables. The degrees of toxicity shown in the tables are based on the toxicity scale National Cancer Institute (NCI-CTC).

Table 1

Modification of the dosage regimen in connection with the development of palmar-plantar syndrome and stomatitis

Table 2

Modification of the dosage regimen due to the development of hematological toxicity (in breast cancer, ovarian cancer)

Table 3

Modification of the dosage regimen for multiple myeloma

*For more information about the bortezomib regimen and dose adjustment, see the bortezomib instructions for use ("Dosage and administration").

If a patient with multiple myeloma receiving combination therapy with Doxorubicin hydrochloride^® and bortezomib, develops palmar-plantar syndrome or stomatitis, then the dose of the drug Doxorubicin hydrochloride^® it should be adjusted as indicated in table 1.

Patients with impaired liver function. When the serum bilirubin content is from 1.2 to 3 mg/dl, the calculated dose is reduced by 25%. If the bilirubin content exceeds 3 mg/dl, the calculated dose is reduced by 50%. If the patient has well tolerated the administration of this dose (without hyperbilirubinemia or increased activity of liver enzymes in the blood serum), then the next dose is increased to the previous level (i.e., if the dose is reduced by 25%, it is increased to the full dose, if the dose is reduced by 50%, it is increased to 75% of the full dose). With good tolerability in subsequent cycles, the dose can be increased to the full dose. Doxorubicin hydrochloride^® it can be prescribed to patients with liver metastases with concomitant hyperbilirubinemia and increased activity of liver enzymes, up to 4 times higher than the ULN. Before administration of Doxorubicin hydrochloride^® It is necessary to conduct a clinical and laboratory study of liver function, including the determination of the activity of ALT/AST, alkaline phosphatase, and bilirubin.

Patients with impaired renal function. Correction of the dosage regimen is not required. There are no data on the pharmacokinetics of the drug in patients with a creatinine Cl of less than 30 ml/min.

Patients with AIDS-associated Kaposi's sarcoma and splenectomy. Since there is currently no clinical data on the use of the drug Doxorubicin hydrochloride^® for the treatment of this group of patients, the use of the drug Doxorubicin hydrochloride^® in these patients, it is not recommended.

Children. Limited safety data obtained in phase I studies indicate that doses up to 60 mg / m every 4 weeks are well tolerated in pediatric practice, however, the effectiveness of the drug Doxorubicin hydrochloride^® for the treatment of patients under 18 years of age is not established.

Adult patients. In patients aged 21 to 75 years of significant differences in the pharmacokinetics of the drug Doxorubicin hydrochloride^® not detected.

Rules for the preparation and administration of solution for infusions

Do not use the drug with signs of precipitation or the presence of suspended particles.

When using the drug, it is necessary to follow the rules for working with antitumor drugs. It is necessary to use gloves. In case of ingestion of Doxorubicin hydrochloride^® on the skin or mucous membranes, immediately wash this area with soap and water.

Determine the dose of Doxorubicin hydrochloride^®, required for the introduction. The required volume of the drug is collected in a sterile syringe. All manipulations should be carried out with strict compliance with the rules of asepsis (the drug does not contain preservatives and bacteriostatic additives).

It is recommended to administer Doxorubicin hydrochloride^® through the side port of the infusion system, through which a 5% dextrose solution is injected to achieve greater dilution and minimize the risk of thrombosis and extravasation. The infusion can be carried out in the peripheral vein.

Doxorubicin hydrochloride^® you can not enter in / m or p / K.

Do not use for the administration of Doxorubicin hydrochloride^® infusion systems with a built-in filter.

It is recommended to administer Doxorubicin hydrochloride^® immediately after dilution with 5% dextrose solution for infusions. In cases where this is not possible, the prepared solution can be stored at a temperature of 2-8 °C and used for 24 hours.

In/in, intravesical, in / a.

Adriblastin can be used both as monotherapy and in combination with other cytostatics in different doses, depending on the treatment regimen.

In / in the introduction.

As monotherapy, the recommended standard dose per cycle is 60-75 mg / m² the surface of the body. Usually, the drug is administered once during the cycle, but the cycle dose can be divided into several injections (for example, administered during the first 3 consecutive days or on the 1st and 8th day of the cycle). The cycles are repeated every 3-4 weeks. A weekly regimen of 10-20 mg/m is also used.², in combination with other antitumor drugs - in a cyclic dose of 30-60 mg / m² every 3-4 weeks.

Repeated administration of the drug is possible only when all signs of toxicity (especially gastrointestinal and hematological) disappear.

In patients with impaired liver function with an increased level of bilirubin in the blood serum, the dose of doxorubicin decreases depending on the indicators of the level of total bilirubin: at the level of bilirubin in the blood serum of 1.2–3 mg/dl — by 50%, above 3 mg/dl — by 75%.

It is recommended to prescribe lower doses or increase the intervals between cycles in patients who have previously received massive antitumor therapy, in children, in elderly patients, in obese patients (if the body weight is more than 130% of the ideal, there is a decrease in the systemic clearance of Adriblastin), as well as in patients with tumor infiltration of the bone marrow.

Intravenous administration of Adriblastine should be carried out with caution. To reduce the risk of thrombosis and extravasation, it is recommended to administer Adriblastin through the tube of the system for intravenous administration, during an infusion of 0.9% sodium chloride solution or 5% glucose solution, for 3-5 minutes.

The total dose of doxorubicin should not exceed 550 mg / m².

In patients who have previously received radiation therapy on the mediastinal area/pericardial area or treated with other cardiotoxic drugs, if necessary, the total dose of doxorubicin exceeds 450 mg / m² the administration of the drug should be carried out under strict monitoring of heart function.

Introduction to the bladder.

Introduction to the bladder is used in the treatment of superficial tumors of the bladder, as well as as a preventive measure, to reduce the likelihood of relapse after transurethral resection.

Intravesical-the recommended dose is 30-50 mg per instillation, with intervals between injections from 1 week to 1 month, depending on the goals of therapy (treatment or prevention).

The recommended concentration of the solution is 1 mg / ml of water for injection or 0.9% sodium chloride solution. After instillation is complete, patients should turn over from side to side every 15 minutes to ensure a uniform effect of the drug on the bladder mucosa. As a rule, the drug should be in the bladder for 1-2 hours. At the end of instillation, the patient should empty the bladder.

To prevent excessive dilution of the drug in the urine, patients should be warned that they should refrain from taking fluids for 12 hours before instillation. The systemic absorption of Adriblastin during instillation into the bladder is very low.

In cases of local toxic effects (chemical cystitis, which can be manifested by dysuria, polyuria, nycturia, painful urination, hematuria, discomfort in the bladder, necrosis of the bladder wall), the dose intended for instillation should be dissolved in 50-100 ml of saline solution.

Special attention should be paid to problems associated with catheterization (for example, with obstruction of the urethra due to massive intravesical tumors).

B / a introduction.

In patients with hepatocellular cancer, to ensure intensive local exposure while reducing the overall toxic effect, Adriblastin can be administered intravenously into the main hepatic artery at a dose of 30-150 mg/m² at intervals of 3 weeks to 3 months. Higher doses should be used only in cases where extracorporeal excretion of the drug is carried out simultaneously.

Since this method is potentially dangerous, and when it is used, widespread tissue necrosis can occur, intravenous administration can only be carried out by doctors who are proficient in this technique.

I / v, 75 mg / m² every 3rd week.

Acute myelosuppression (including as a result of chemo-or radiation therapy), previous treatment with cumulative doses of pharmorubicin, daunoblastin or even adriblastin, bladder tumors complicated by narrowing of the urethra, urinary tract infections (intravesical instillation), cardiomyopathy (including in the anamnesis).

Hypersensitivity, impaired liver and kidney function, leukopenia, thrombocytopenia, anemia, myocarditis, myocardial infarction, arrhythmia, cystitis (with intravesical use), pregnancy, breast-feeding.

Data on adverse reactions observed in clinical trials. The following are the adverse events reported in clinical trials and systematized for each of the organ systems, depending on the frequency of occurrence, using the following classification: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including isolated cases.

Adverse events observed in the course of clinical studies of the use of the drug Kelix^® for the treatment of breast cancer patients

Infections and infestations: often — pharyngitis, folliculitis, fungal infections, feverish rashes on the skin (non-herpetic), upper respiratory tract infections.

From the blood and lymphatic system: often-leukopenia, anemia, neutropenia, thrombocytopenia, thrombocytemia.

From the nervous system: often-paresthesia, peripheral neuropathy, hot flashes, infrequently-drowsiness.

On the part of the visual organ: often-lacrimation, blurred vision.

From the heart: often-ventricular arrhythmia.

From the respiratory system, chest and mediastinal organs: often-shortness of breath, nosebleeds.

From the side of metabolism and nutrition: very often — anorexia.

From the gastrointestinal tract: very often-nausea, vomiting, stomatitis, often-ulceration of the oral mucosa, abdominal pain, constipation, diarrhea, dyspepsia, pain in the oral cavity.

From the skin and subcutaneous tissues: very often-alopecia, palmar-plantar syndrome, rash, often-erythema, dry skin, pigmentation disorders, itching, discoloration of the skin, bullous rash, dermatitis, erythematous rash, nail lesions, scaly skin.

Musculoskeletal and connective tissue disorders: often-leg cramps, bone pain, muscle pain.

On the part of the reproductive system and breast: often-pain in the mammary gland.

General disorders and reactions at the injection site: very often — fatigue, asthenia, inflammation of the mucous membranes, often-weakness, fever, pain, weight loss, swelling (including in the legs).

Influence on the results of laboratory tests: clinically significant deviations of laboratory parameters (grade III and IV) in this group of breast cancer patients included increases in the concentration of total bilirubin (2.4%) and AST activity (1.6%). The increase in ALT activity was less frequent (<1 %). There was no clinically significant increase in serum creatinine.

Adverse events observed in the course of clinical studies of the use of the drug Kelix^® for the treatment of ovarian cancer patients

Infections and infestations: often-infections, candidiasis of the oral mucosa, shingles, urinary tract infections, other infections (including fungal infections, lower respiratory tract infections).

From the blood and lymphatic system: very often — leukopenia, anemia, neutropenia, thrombocytopenia, often-hypochromic anemia.

From the nervous system: often-paresthesia, drowsiness, headache, dizziness, neuropathy, increased blood pressure.

From the respiratory system, chest and mediastinal organs: often — pharyngitis, shortness of breath, increased cough.

From the gastrointestinal tract: very often — stomatitis, constipation, diarrhea, nausea, vomiting, often-abdominal pain, dyspepsia, ulceration of the oral cavity, esophagitis, gastritis, dysphagia, dry mouth, flatulence, gingivitis, perversion of taste.

From the skin and subcutaneous tissues: very often-palmar-plantar syndrome, alopecia, rash, often-dry skin, discoloration of the skin, vesiculobullosis rash, itching, exfoliative dermatitis, skin disorders, maculopapular rash, sweating, acne, skin ulcers.

On the part of the immune system: often-allergic reactions.

From the side of metabolism and nutrition: very often-anorexia, often-dehydration, cachexia.

Mental disorders: often-anxiety, depression, insomnia.

On the part of the visual organ: often-conjunctivitis.

From the heart: often-cardiovascular disorders.

From the side of the vessels: often-vasodilation.

Musculoskeletal and connective tissue disorders: often-back pain, myalgia.

From the kidneys and urinary tract: often-dysuria.

From the genitals and breast: often-vaginitis.

General disorders and disorders at the injection site: very often — asthenia, violation of the mucous membranes, often-fever, pain, chills, chest pain, malaise, peripheral edema.

Influence on the results of laboratory and instrumental studies: often-weight loss. Clinically significant deviations of laboratory parameters observed in patients with ovarian cancer during clinical trials of the drug Kelix^®, included an increase in total bilirubin (usually in patients with liver metastases — 5%) and serum creatinine levels (5%). Increases in AST were less frequent (<1%). Sepsis in leukopenia was observed infrequently (<1%).

Adverse events observed in the course of clinical studies of the use of the drug Kelix^® for the treatment of patients with multiple myeloma

Infections and infestations: often — herpes simplex, shingles, nasopharyngitis, oral candidiasis, pneumonia, upper respiratory tract infection.

From the blood and lymphatic system: very often — anemia, neutropenia, thrombocytopenia, often-febrile neutropenia, leukopenia, lymphopenia.

From the side of metabolism and nutrition: very often-anorexia, often-decreased appetite, dehydration, hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia.

Mental disorders: often-anxiety, insomnia.

From the nervous system: very often-headache, neuralgia, peripheral sensory neuropathy, often-dizziness, dysesthesia, dysgeusia, hypesthesia, lethargy, neuropathy, paresthesia, peripheral neuropathy, polyneuropathy, fainting.

On the part of the visual organ: often-conjunctivitis.

From the side of the vessels: often-hot flashes, low blood pressure, increased blood pressure, orthostatic hypotension, phlebitis.

From the respiratory system, chest and mediastinal organs: often-cough, shortness of breath, nosebleeds, shortness of breath during exercise.

From the gastrointestinal tract: very often-nausea, vomiting, diarrhea, stomatitis, constipation, often-abdominal pain, dyspepsia, pain in the upper abdomen, ulceration of the oral cavity, dry mouth, dysphagia, aphthous stomatitis.

From the skin and subcutaneous tissues: very often-palmar-plantar syndrome, rash, often-dry skin, itching, papular rash, allergic dermatitis, erythema, hyperpigmentation of the skin, petechiae, alopecia, drug rash.

Musculoskeletal and connective tissue disorders: often-arthralgia, muscle spasms, muscle weakness, musculoskeletal pain in the chest, musculoskeletal pain, myalgia, pain in the extremities.

On the part of the reproductive system and breast: often-erythema of the scrotum.

General disorders and disorders at the injection site: very often — asthenia, fatigue, pyrexia, often-chills, hyperthermia, flu-like disease, malaise, peripheral edema.

Influence on the results of laboratory and instrumental studies: often — an increase in ALT activity in the blood, an increase in AST activity in the blood, an increase in the concentration of creatinine in the blood, a decrease in the ejection fraction, a decrease in body weight.

Adverse events observed in the course of clinical studies of the use of the drug Kelix^® for the treatment of patients with AIDS-associated Kaposi's sarcoma

Infections and infestations: often-candidiasis of the oral cavity.

From the blood and lymphatic system: very often — neutropenia, anemia, leukopenia, often-thrombocytopenia.

From the side of metabolism and nutrition: often-anorexia.

Mental disorders: often-confusion.

From the nervous system: often-dizziness, infrequently-paresthesia.

On the part of the visual organ: often-retinitis.

From the side of the vessels: often-vasodilation.

From the respiratory system, chest and mediastinal organs: often-shortness of breath.

From the gastrointestinal tract: very often-nausea, often-diarrhea, stomatitis, vomiting, ulceration of the oral mucosa, abdominal pain, glossitis, constipation, nausea and vomiting.

From the skin and subcutaneous tissues: often — alopecia, rash, infrequently-palmar-plantar syndrome.

General disorders and disorders at the injection site: often-asthenia, fever, acute reactions to the infusion.

Influence on the results of laboratory and instrumental studies: often — weight loss.

Hematological toxic events may require dose reduction or suspension of therapy. It is necessary to temporarily suspend therapy with the drug Kelix^® in patients with an absolute neutrophil count <1000 / mm³ and / or platelet count <50000 / mm³ G-CSF (or GM-CSF) can be used in concomitant therapy to maintain the number of shaped elements at an absolute neutrophil count of <1000 / mm.³ in subsequent cycles.

Respiratory side effects have been reported frequently (≥5%) in clinical trials of the drug Kelix^® and may be associated with opportunistic infections in the AIDS patient population. Opportunistic infections (OI) have been reported in patients with AIDS-associated Kaposi's sarcoma after the use of the drug Kelix^®, and are often observed in patients with HIV-related immunodeficiency. The most frequently reported OI in clinical studies were: candidiasis, CMV infection, herpes simplex, pneumonia caused by Pneumocystis carinii and the complex Mycobacterium avium. Clinically significant laboratory disorders were often observed (≥5%) in clinical trials of the drug Kelix^®. These included an increase in the activity of alkaline phosphatase, an increase in the activity of AST and the concentration of bilirubin, which were considered to be associated with the underlying disease, and not with the use of the drug Kelix^®. Decreases in hemoglobin and platelet count were rare (<5%). Sepsis associated with leukopenia was rare (<1%). Some of the described deviations could be associated with the presence of HIV infection, and not with taking the drug Kelix^®.

Post-registration surveillance data

Adverse reactions observed during post-marketing use of the drug Kelix^® and systematized with respect to each of the organ systems depending on the frequency of occurrence, using the following classification are given below: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000), very rarely (<1/10000), including isolated cases.

From the side of the vessels: patients with malignant tumors have an increased risk of developing thromboembolism. Infrequently — in patients taking the drug Kelix^®, there are cases of thrombophlebitis and venous thrombosis, as well as pulmonary embolism.

From the skin and subcutaneous tissues: very rarely — serious skin disorders, including polymorphic erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Secondary neoplasms of the oral cavity: very rarely — with prolonged (more than one year) use of the drug Kelix^® or if the total dose of the drug Kelix is reached^® more than 720 mg / m² patients have had cases of secondary oral cancer.

Data on adverse reactions observed in clinical trials. The following are the adverse events reported in clinical trials and systematized for each of the organ systems, depending on the frequency of occurrence, using the following classification: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including isolated cases.

Adverse events observed in the course of clinical studies of the use of the drug Doxorubicin hydrochloride^® for the treatment of breast cancer patients

Infections and infestations: often — pharyngitis, folliculitis, fungal infections, feverish rashes on the skin (non-herpetic), upper respiratory tract infections.

From the blood and lymphatic system: often-leukopenia, anemia, neutropenia, thrombocytopenia, thrombocytemia.

From the nervous system: often-paresthesia, peripheral neuropathy, hot flashes, infrequently-drowsiness.

On the part of the visual organ: often-lacrimation, blurred vision.

From the heart: often-ventricular arrhythmia.

From the respiratory system, chest and mediastinal organs: often-shortness of breath, nosebleeds.

From the side of metabolism and nutrition: very often — anorexia.

From the gastrointestinal tract: very often-nausea, vomiting, stomatitis, often-ulceration of the oral mucosa, abdominal pain, constipation, diarrhea, dyspepsia, pain in the oral cavity.

From the skin and subcutaneous tissues: very often-alopecia, palmar-plantar syndrome, rash, often-erythema, dry skin, pigmentation disorders, itching, discoloration of the skin, bullous rash, dermatitis, erythematous rash, nail lesions, scaly skin.

Musculoskeletal and connective tissue disorders: often-leg cramps, bone pain, muscle pain.

On the part of the reproductive system and breast: often-pain in the mammary gland.

General disorders and reactions at the injection site: very often — fatigue, asthenia, inflammation of the mucous membranes, often-weakness, fever, pain, weight loss, swelling (including in the legs).

Influence on the results of laboratory tests: clinically significant deviations of laboratory parameters (grade III and IV) in this group of breast cancer patients included increases in the concentration of total bilirubin (2.4%) and AST activity (1.6%). The increase in ALT activity was less frequent (<1 %). There was no clinically significant increase in serum creatinine.

Adverse events observed in the course of clinical studies of the use of the drug Doxorubicin hydrochloride^® for the treatment of ovarian cancer patients

Infections and infestations: often-infections, candidiasis of the oral mucosa, shingles, urinary tract infections, other infections (including fungal infections, lower respiratory tract infections).

From the blood and lymphatic system: very often — leukopenia, anemia, neutropenia, thrombocytopenia, often-hypochromic anemia.

From the nervous system: often-paresthesia, drowsiness, headache, dizziness, neuropathy, increased blood pressure.

From the respiratory system, chest and mediastinal organs: often — pharyngitis, shortness of breath, increased cough.

From the gastrointestinal tract: very often — stomatitis, constipation, diarrhea, nausea, vomiting, often-abdominal pain, dyspepsia, ulceration of the oral cavity, esophagitis, gastritis, dysphagia, dry mouth, flatulence, gingivitis, perversion of taste.

From the skin and subcutaneous tissues: very often-palmar-plantar syndrome, alopecia, rash, often-dry skin, discoloration of the skin, vesiculobullosis rash, itching, exfoliative dermatitis, skin disorders, maculopapular rash, sweating, acne, skin ulcers.

On the part of the immune system: often-allergic reactions.

From the side of metabolism and nutrition: very often-anorexia, often-dehydration, cachexia.

Mental disorders: often-anxiety, depression, insomnia.

On the part of the visual organ: often-conjunctivitis.

From the heart: often-cardiovascular disorders.

From the side of the vessels: often-vasodilation.

Musculoskeletal and connective tissue disorders: often-back pain, myalgia.

From the kidneys and urinary tract: often-dysuria.

From the genitals and breast: often-vaginitis.

General disorders and disorders at the injection site: very often — asthenia, violation of the mucous membranes, often-fever, pain, chills, chest pain, malaise, peripheral edema.

Influence on the results of laboratory and instrumental studies: often-weight loss. Clinically significant deviations of laboratory parameters observed in patients with ovarian cancer during clinical trials of the drug Doxorubicin hydrochloride^®, included an increase in total bilirubin (usually in patients with liver metastases — 5%) and serum creatinine levels (5%). Increases in AST were less frequent (<1%). Sepsis in leukopenia was observed infrequently (<1%).

Adverse events observed in the course of clinical studies of the use of the drug Doxorubicin hydrochloride^® for the treatment of patients with multiple myeloma

Infections and infestations: often — herpes simplex, shingles, nasopharyngitis, oral candidiasis, pneumonia, upper respiratory tract infection.

From the blood and lymphatic system: very often — anemia, neutropenia, thrombocytopenia, often-febrile neutropenia, leukopenia, lymphopenia.

From the side of metabolism and nutrition: very often-anorexia, often-decreased appetite, dehydration, hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia.

Mental disorders: often-anxiety, insomnia.

From the nervous system: very often-headache, neuralgia, peripheral sensory neuropathy, often-dizziness, dysesthesia, dysgeusia, hypesthesia, lethargy, neuropathy, paresthesia, peripheral neuropathy, polyneuropathy, fainting.

On the part of the visual organ: often-conjunctivitis.

From the side of the vessels: often-hot flashes, low blood pressure, increased blood pressure, orthostatic hypotension, phlebitis.

From the respiratory system, chest and mediastinal organs: often-cough, shortness of breath, nosebleeds, shortness of breath during exercise.

From the gastrointestinal tract: very often-nausea, vomiting, diarrhea, stomatitis, constipation, often-abdominal pain, dyspepsia, pain in the upper abdomen, ulceration of the oral cavity, dry mouth, dysphagia, aphthous stomatitis.

From the skin and subcutaneous tissues: very often-palmar-plantar syndrome, rash, often-dry skin, itching, papular rash, allergic dermatitis, erythema, hyperpigmentation of the skin, petechiae, alopecia, drug rash.

Musculoskeletal and connective tissue disorders: often-arthralgia, muscle spasms, muscle weakness, musculoskeletal pain in the chest, musculoskeletal pain, myalgia, pain in the extremities.

On the part of the reproductive system and breast: often-erythema of the scrotum.

General disorders and disorders at the injection site: very often — asthenia, fatigue, pyrexia, often-chills, hyperthermia, flu-like disease, malaise, peripheral edema.

Influence on the results of laboratory and instrumental studies: often — an increase in ALT activity in the blood, an increase in AST activity in the blood, an increase in the concentration of creatinine in the blood, a decrease in the ejection fraction, a decrease in body weight.

Adverse events observed in the course of clinical studies of the use of the drug Doxorubicin hydrochloride^® for the treatment of patients with AIDS-associated Kaposi's sarcoma

Infections and infestations: often-candidiasis of the oral cavity.

From the blood and lymphatic system: very often — neutropenia, anemia, leukopenia, often-thrombocytopenia.

From the side of metabolism and nutrition: often-anorexia.

Mental disorders: often-confusion.

From the nervous system: often-dizziness, infrequently-paresthesia.

On the part of the visual organ: often-retinitis.

From the side of the vessels: often-vasodilation.

From the respiratory system, chest and mediastinal organs: often-shortness of breath.

From the gastrointestinal tract: very often-nausea, often-diarrhea, stomatitis, vomiting, ulceration of the oral mucosa, abdominal pain, glossitis, constipation, nausea and vomiting.

From the skin and subcutaneous tissues: often — alopecia, rash, infrequently-palmar-plantar syndrome.

General disorders and disorders at the injection site: often-asthenia, fever, acute reactions to the infusion.

Influence on the results of laboratory and instrumental studies: often — weight loss.

Hematological toxic events may require dose reduction or suspension of therapy. Therapy with Doxorubicin hydrochloride should be temporarily suspended^® in patients with an absolute neutrophil count <1000 / mm³ and / or platelet count <50000 / mm³ G-CSF (or GM-CSF) can be used in concomitant therapy to maintain the number of shaped elements at an absolute neutrophil count of <1000 / mm.³ in subsequent cycles.

Respiratory side effects have been reported frequently (≥5%) in clinical trials of Doxorubicin hydrochloride^® and may be associated with opportunistic infections in the AIDS patient population. Opportunistic infections (OI) have been reported in patients with AIDS-associated Kaposi's sarcoma after administration of Doxorubicin hydrochloride^®, and are often observed in patients with HIV-related immunodeficiency. The most frequently reported OI in clinical studies were: candidiasis, CMV infection, herpes simplex, pneumonia caused by Pneumocystis carinii and the complex Mycobacterium avium. Clinically significant laboratory abnormalities were frequently reported (≥5%) in clinical trials of Doxorubicin hydrochloride^®. These included increased activity of the alkaline phosphatase, increased activity of AST, and bilirubin concentrations, which were considered to be associated with the underlying disease, rather than with the drug Doxorubicin hydrochloride^®. Decreases in hemoglobin and platelet count were rare (<5%). Sepsis associated with leukopenia was rare (<1%). Some of the described abnormalities could be associated with the presence of HIV infection, and not with the use of the drug Doxorubicin hydrochloride^®.

Post-registration surveillance data

Adverse reactions observed during post-marketing use of Doxorubicin hydrochloride^® and systematized with respect to each of the organ systems depending on the frequency of occurrence, using the following classification are given below: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000), very rarely (<1/10000), including isolated cases.

From the side of the vessels: patients with malignant tumors have an increased risk of developing thromboembolism. Infrequently - in patients taking the drug Doxorubicin hydrochloride^®, there are cases of thrombophlebitis and venous thrombosis, as well as pulmonary embolism.

From the skin and subcutaneous tissues: very rarely — serious skin disorders, including polymorphic erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Secondary neoplasms of the oral cavity: very rarely — with prolonged (more than one year) use of the drug Doxorubicin hydrochloride^® or if the total dose of Doxorubicin hydrochloride is reached^® more than 720 mg / m² patients have had cases of secondary oral cancer.

With intravenous administration — myelosuppression, cardiac disorders, sometimes manifested a few weeks after discontinuation of therapy (heart failure), alopecia (in 85% of patients), cessation of hair growth (including beard), stomatitis (5-10 days after the first administration) with painful erosions, especially on the lateral surfaces of the tongue, in the sublingual area, nausea, vomiting, diarrhea, etc.gastrointestinal disorders, severe tissue damage, including necrosis (when the solution enters the tissues, especially repeated use of the same vein), venous sclerosis.

When administered inside the bladder — burning in the bladder and urethra, urination disorders (soreness, difficulty, frequency, etc.), hematuria.

Stomatitis, nausea, vomiting, alopecia, heart failure, heart pain, red urine staining, leukopenia, thrombocytopenia, anemia, allergic reactions.

With intravenous administration of the drug Kelix^® The plasma concentration of doxorubicin and AUC, which are mainly related to pegylated liposomal doxorubicin (90 to 95% of the measured doxorubicin, respectively), are significantly higher than with equivalent doses of traditional (non-pegylated non-liposomal) doxorubicin.

Pharmacokinetic profile of the drug Kelix^® indicates that the clearance of doxorubicin from the blood plasma is determined by the liposomal carrier. Doxorubicin becomes available only after the liposomes leave the vascular bed and enter the tissues.

In low doses (10-20 mg / m²) Kelix^® demonstrates linear pharmacokinetics, at higher doses (20-60 mg / m²) - non-linear. Pharmacokinetic parameters when administered at a dose of 10 to 60 mg / m²: doxorubicin clearance-average 0.03 l / h / m (0.0080,152 l/h/m²), V_d - 1.93 l / m² (0.96-3.85 l / m²), T_1/2 - 73.9 hours (24-231 hours).

Pharmacokinetic parameters in patients with impaired liver function and hyperbilirubinemia differ slightly from the pharmacokinetic parameters of the normal concentration of total bilirubin.

Renal insufficiency (creatinine Cl 30-156 ml/min) does not affect the pharmacokinetic parameters. There are no data on the pharmacokinetics of the drug in patients with creatinine Cl less than 30 ml / min.

The age of patients (21-75 years) does not significantly affect the pharmacokinetic parameters of the drug Kelix^®.

With intravenous administration of the drug Doxorubicin hydrochloride^® The plasma concentration of doxorubicin and AUC, which are mainly related to pegylated liposomal doxorubicin (90 to 95% of the measured doxorubicin, respectively), are significantly higher than with equivalent doses of traditional (non-pegylated non-liposomal) doxorubicin.

Pharmacokinetic profile of Doxorubicin hydrochloride^® indicates that the clearance of doxorubicin from the blood plasma is determined by the liposomal carrier. Doxorubicin becomes available only after the liposomes leave the vascular bed and enter the tissues.

In low doses (10-20 mg / m²) Doxorubicin hydrochloride^® demonstrates linear pharmacokinetics, at higher doses (20-60 mg / m²) - non-linear. Pharmacokinetic parameters when administered at a dose of 10 to 60 mg / m²: doxorubicin clearance-average 0.03 l / h / m (0.0080,152 l/h/m²), V_d - 1.93 l / m² (0.96-3.85 l / m²), T_1/2 - 73.9 hours (24-231 hours).

Pharmacokinetic parameters in patients with impaired liver function and hyperbilirubinemia differ slightly from the pharmacokinetic parameters of the normal concentration of total bilirubin.

Renal insufficiency (creatinine Cl 30-156 ml/min) does not affect the pharmacokinetic parameters. There are no data on the pharmacokinetics of the drug in patients with creatinine Cl less than 30 ml / min.

The age of patients (21-75 years) does not significantly affect the pharmacokinetic parameters of the drug Doxorubicin hydrochloride^®.

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from Streptomyces peucetius var. caesius. The exact mechanism of the antitumor action of doxorubicin is unknown. It is believed that the cytotoxic effect is due to its ability to inhibit the synthesis of DNA, RNA and proteins by introducing doxorubicin between adjacent base pairs of the DNA double helix, which prevents the helix from unfolding for subsequent replication. Kelix^® it is a pegylated liposomal form of doxorubicin that circulates in the blood for a long time and provides a higher concentration of doxorubicin in tumor tissue than in normal tissues. Liposomes contain surface-bound hydrophilic polymers of methoxypolyethylene glycol (MPEG). These linear groups of MPEGs create a protective shell protruding above the surface of the liposomes, which reduces the possibility of interaction between the lipid bilayer membrane and plasma components, which protects the liposomes from recognition by the phagocytic system and allows to prolong the circulation time of doxorubicin in the bloodstream. Pegylated liposomes also have a low-permeability lipid matrix and an internal water buffer system, which in combination allows you to keep doxorubicin inside the liposome during its circulation in the bloodstream. The relatively small size of the pegylated liposomes (the average diameter is approximately 100 nm) allows them to penetrate through the defects of the blood vessels of the tumor. The results of experimental studies indicate the penetration of pegylated liposomes from blood vessels and their accumulation in tumors

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from Streptomyces peucetius var. caesius. The exact mechanism of the antitumor action of doxorubicin is unknown. It is believed that the cytotoxic effect is due to its ability to inhibit the synthesis of DNA, RNA and proteins by introducing doxorubicin between adjacent base pairs of the DNA double helix, which prevents the helix from unfolding for subsequent replication. Doxorubicin hydrochloride^® it is a pegylated liposomal form of doxorubicin that circulates in the blood for a long time and provides a higher concentration of doxorubicin in tumor tissue than in normal tissues. Liposomes contain surface-bound hydrophilic polymers of methoxypolyethylene glycol (MPEG). These linear groups of MPEGs create a protective shell protruding above the surface of the liposomes, which reduces the possibility of interaction between the lipid bilayer membrane and plasma components, which protects the liposomes from recognition by the phagocytic system and allows to prolong the circulation time of doxorubicin in the bloodstream. Pegylated liposomes also have a low-permeability lipid matrix and an internal water buffer system, which in combination allows you to keep doxorubicin inside the liposome during its circulation in the bloodstream. The relatively small size of the pegylated liposomes (the average diameter is approximately 100 nm) allows them to penetrate through the defects of the blood vessels of the tumor. The results of experimental studies indicate the penetration of pegylated liposomes from blood vessels and their accumulation in tumors

Along with antitumor, it has an immunosuppressive effect.

With the combined use of the drug Kelix^® No increase in toxicity was found with cyclophosphamide or taxanes in patients with solid tumors (including ovarian cancer and breast cancer). However, it should be taken into account that Kelix^® Like other doxorubicin hydrochloride preparations, it may increase the toxic effect of other antitumor agents.

There are reports of exacerbation of cyclophosphamide-induced hemorrhagic cystitis and increased hepatotoxicity of mercaptopurine in patients with AIDS-associated Kaposi's sarcoma when treated with standard doxorubicin hydrochloride. Caution should be exercised when concomitantly using any other cytostatics, especially myelotoxic agents.

The drug should not be mixed with other solutions, except for 5% dextrose solution for infusions.

With the combined use of the drug Doxorubicin hydrochloride^® No increase in toxicity was found with cyclophosphamide or taxanes in patients with solid tumors (including ovarian cancer and breast cancer). However, it should be considered that Doxorubicin hydrochloride^® Like other doxorubicin hydrochloride preparations, it may increase the toxic effect of other antitumor agents.

There are reports of exacerbation of cyclophosphamide-induced hemorrhagic cystitis and increased hepatotoxicity of mercaptopurine in patients with AIDS-associated Kaposi's sarcoma when treated with standard doxorubicin hydrochloride. Caution should be exercised when concomitantly using any other cytostatics, especially myelotoxic agents.

The drug should not be mixed with other solutions, except for 5% dextrose solution for infusions.

It can be used in combination with other chemotherapeutic antitumor agents.