Doxorubicin

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Doxorubicin: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Drug interactions
10. Analogs
11. Terms and conditions of storage
12. Terms of dispensing from pharmacies
13. Reviews
14. Price in pharmacies

Latin name: Doxorubicin

ATX code: L01DB01

Active ingredient: doxorubicin (doxorubicin)

Producer: St. Petersburg NIIVS, JSC Pharmstandard, LLC Lance-Pharm (Russia), PJSC Pharmstandard-Biolek (Ukraine)

Description and photo update: 2019-18-09

Lyophilisate for preparation of solution for intravascular and intravesical administration Doxorubicin

Doxorubicin is an anthracycline antitumor antibiotic with antiproliferative and antimitotic effects.

Release form and composition

Dosage forms:

Lyophilisate for preparing a solution for intravascular and intravesical administration (10 ml in vials, 10 pcs in a cardboard box);
Concentrate for the preparation of a solution for intravascular and intravesical administration (5 ml in glass bottles, in a cardboard box 1 or 10 pcs.; 25 or 50 ml in glass bottles, in a cardboard box 1 pc.).

The active substance is doxorubicin hydrochloride:

1 bottle of lyophilisate - 10 mg;
1 ml of concentrate - 2 mg.

The auxiliary component of the lyophilisate is mannitol.

Pharmacological properties

Pharmacodynamics

Doxorubicin is obtained through chemical synthesis from the substance daunorubicin hydrochloride. It is characterized by antiproliferative and antimitotic effects, the mechanism of which is a direct effect on cell membranes with subsequent suppression of nucleic acid production, the formation of free radicals and interaction with DNA. Tumor cells show drug sensitivity in the S and G2 phases.

Pharmacokinetics

The degree of absorption of doxorubicin is quite high, and it is characterized by uniform distribution in the body. The substance does not cross the blood-brain barrier and binds to plasma proteins by about 75%. The drug is metabolized in the liver to form the main metabolite of doxorubicinol, which has pharmacological activity.

Doxorubicin is involved in the enzymatic recovery processes caused by the action of dehydrogenases, reductases and oxidases, which contributes to the formation of free radicals and manifestations of the cardiotoxic effect. After intravenous administration, the substance is rapidly excreted from the bloodstream, concentrating in the myocardium, lungs, spleen, liver, and kidneys. The half-lives of doxorubicin and doxorubicinol vary from 20 to 48 hours. Doxorubicin is excreted unchanged within 7 days (approximately 40% of the administered dose). From 5 to 12% of the active substance and its metabolites are excreted in the urine for 5 days.

In children over 2 years of age, the clearance of doxorubicin exceeds this indicator in adult patients. The clearance in children under 2 years of age is almost the same as in adults. In elderly patients, there is no need for dose adjustment. On average, the clearance of doxorubicin in male patients is much higher than in female patients. However, the terminal half-life of the drug in men is longer than in women (54 and 35 hours, respectively).

The effect of the patient's race on the pharmacokinetic parameters of doxorubicin has not yet been studied. In patients with liver dysfunctions, the clearance of doxorubicin and its main metabolite is somewhat reduced. It is not known how changes in renal function affect the pharmacokinetics of the drug.

Indications for use

According to the instructions, Doxorubicin is used in the treatment of the following oncological diseases: osteosarcoma, soft tissue sarcoma, Ewing's sarcoma, Kaposi's sarcoma (in AIDS patients), malignant thymoma, retinoblastoma, hepatoblastoma, neuroblastoma, Wilms' tumor, trophoblastic tumors, acute leucocytosis acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, multiple myeloma, lymphogranulomatosis, small cell lung cancer, breast cancer, thyroid cancer, esophageal cancer, primary hepatocellular cancer, stomach cancer, pancreatic cancer, ovarian cancer, germ cell tumor of the testicle, prostate cancer, cervical cancer, adrenal cancer, bladder cancer (including prevention of relapse after surgery).

Contraindications

Expressed functional depression of the bone marrow against the background of the use of radiation therapy and other chemotherapeutic agents;
Leukopenia;
Acute hepatitis;
Severe liver dysfunction;
Thrombocytopenia;
Severe heart disease, including severe rhythm disturbances, myocarditis, acute phase of myocardial infarction;
Anemia;
Previous therapy in limiting total doses with anthracyclines;
The period of pregnancy and breastfeeding;
Hypersensitivity to hydroxybenzoates.

In addition, intravesical administration of the drug is contraindicated in patients with invasive tumors with penetration into the bladder wall, with infections and inflammation of the urinary tract and bladder.

Instructions for the use of Doxorubicin: method and dosage

The lyophilisate is intended for intravesical, intravenous (IV) or intra-arterial (IV) administration.

The use of the drug is indicated both in monotherapy and in combination with other cytostatic agents in doses corresponding to the treatment regimen.

The dose is prescribed individually by the oncologist.

Doxorubicin hydrochloride lyophilisate is reconstituted with water for injection or 0.9% sodium chloride solution immediately before use. The required single dose of the resulting solution is additionally diluted in 0.9% sodium chloride solution in a proportion of not more than 1 mg of the drug per 1 ml.

When administered intravenously, the resulting solution is injected into the injection port of the intravenous infusion system for 3-10 minutes during a rapid infusion of 0.9% sodium chloride solution or 5% dextrose solution. Before insertion, you must make sure that the needle (or catheter) is inserted exactly into the vein. It is undesirable to inject the drug into the veins above the joints or into small veins; it should not be administered into the limbs with impaired lymphatic and venous drainage.

Recommended dosage for intravenous administration:

Monotherapy: for 1 cycle of therapy, 60-75 mg per 1 sq.m. body surface every three weeks, usually, a cyclic dose is administered once, if necessary, it can be divided into several doses, for example, 25-30 mg per 1 sq. m. per day in the first 3 days of the cycle. To reduce the toxic effect, especially the cardiotoxicity of doxorubicin, the drug can be administered weekly at 10-20 mg per square meter;
Combined treatment: doxorubicin hydrochloride is prescribed in a cyclic dose of 30-60 mg per 1 sq.m. every 3-4 weeks. Each subsequent administration of the drug is possible only in the absence of signs of toxicity, especially hematological and gastrointestinal.

The total dose of Doxorubicin should not exceed 550 mg per 1 sq.m.

Patients who previously used other cardiotoxic drugs or received radiation therapy to the pericardial or mediastinal region, the introduction of a total dose of doxorubicin more than 450 mg per 1 sq. M. must be carried out under strict monitoring of heart function.

In patients with impaired liver function, the dose of doxorubicin should be reduced in accordance with the level of total bilirubin concentration in the blood serum: at a bilirubin level of 1.2-3 mg / dl, the decrease is 50% of the recommended dose, if it exceeds 3 mg / dl - by 75%.

It is recommended to increase the intervals between cycles or prescribe lower doses to patients who have previously received extensive antineoplastic therapy, patients with obesity, tumor infiltration of the bone marrow, elderly patients and children.

Doxorubicin administration into the bladder is indicated for the treatment of superficial bladder tumors and for the prevention of recurrence after transurethral resection. Intravesical administration is not suitable for the treatment of invasive tumors with penetration into the muscular wall of the bladder.

The recommended dosage for intravesical administration is 30-50 mg per installation, depending on the purpose of use - treatment or prevention, the break between procedures can be from 1 week to 1 month. To ensure a uniform effect on the entire mucous surface of the bladder, after installation, the patient must change the position of the body from one side to another every fifteen minutes. The drug must be in the bladder for 1-2 hours, then the patient must empty it.

When symptoms of chemical cystitis appear (discomfort in the bladder, dysuria, nocturia, polyuria, hematuria, painful urination, necrosis of the bladder wall), the dose should be dissolved in 50-100 ml of 0.9% sodium chloride solution. It is recommended to pay special attention to the problems of catheterization, including in the treatment of patients with obstruction of the urethra caused by massive intravesical tumors.

Intra-arterial injection into the common hepatic artery is prescribed to patients with hepatocellular cancer in order to provide enhanced local exposure and simultaneously reduce the overall toxic load on the body. The dosage is 30-150 mg per 1 sq. M. with a break from 3 weeks to 3 months. The use of higher doses is allowed only with the possibility of simultaneous extracorporeal excretion of the drug.

Doxorubicin in the form of a concentrate is intended for intravenous and intravesical administration. The dosage regimen depends on the patient's condition, clinical indications and cytotoxic therapy regimen.

Side effects

Doxorubicin use can cause side effects:

From the organs of the gastrointestinal tract (GIT): vomiting, nausea, esophagitis or stomatitis (may appear after 5-10 days, most likely after 3 consecutive days of administration, and cause the development of severe infections), ulceration in the gastrointestinal tract; rarely - diarrhea, anorexia;
On the part of the cardiovascular system and the hematopoietic system: less than 10% of patients who received a total total dose of more than 550 mg per 1 sq. M. body, - congestive heart failure, with manifestations in the form of shortness of breath, rapid or irregular heartbeat, swelling of the ankles and feet (pathology requires immediate discontinuation of the drug, since the development of irreversible, lethal cardiomyopathy may occur, the likelihood of its development after drug withdrawal depends on the dose received and the period treatment); acute ventricular and atrial arrhythmia (usually in the first hours after administration); rarely (after application for several days to several weeks) - toxic myocarditis or pericarditis-myocarditis syndrome (heart failure, pericarditis, tachycardia);reaching a peak by 10-15 days of treatment, leukopenia (blood count is usually restored on day 21 after the end of the drug); thrombocytopenia; in the case of very rapid administration - hyperemia along the vein and blood flow to the face; phlebosclerosis (when injected into small veins or several times in a row into one vein);
From the genitourinary system: nephropathy, hyperuricemia, discoloration of urine (urine becomes reddish, disappearing within 48 hours); with intravesical administration - burning sensation in the urethra and bladder, difficulty, soreness and other disorders of urination, hematuria, cystitis;
Allergic reactions: itching, skin rash, chills, fever, anaphylaxis;
On the part of the skin: darkening of the nails, palms and soles; development of complete and reversible alopecia; relapse of radiation erythema;
Others: cellulite, extravasate, necrosis (if Doxorubicin gets into the surrounding tissues), rarely - lacrimation, conjunctivitis.

Overdose

In acute overdose of Doxorubicin, severe myelosuppression (mainly thrombocytopenia and leukopenia) may develop. Also, the drug, when used in high doses, often demonstrates a pronounced cardiotoxic effect, and also provokes toxic effects from the gastrointestinal tract.

No antidote to doxorubicin is known. When threatening symptoms appear, symptomatic therapy is recommended.

special instructions

Doxorubicin should not be mixed with other anticancer agents in the same syringe.

During the treatment period, it is necessary to regularly (at least 2 times a week) monitor blood counts, heart and liver activity, since cardiotoxicity and suppression of bone marrow hematopoiesis are the dose-limiting factors. The course of repeated therapy can be carried out only in the complete absence of signs of hematotoxicity.

The drug should be prescribed with caution to patients with previous cytotoxic or radiation therapy, elderly or pediatric patients with insufficient bone marrow reserve.

Any dental interventions should be carried out before starting the use of Doxorubicin, since their implementation during the treatment period can increase the risk of microbial infections, bleeding gums and slow down the healing process.

The infusion should be stopped immediately if the drug gets under the skin and continue the injection into another vein.

After chemotherapy, Doxorubicin should be used no earlier than 1 month later.

If the risk of developing nephropathy increases against the background of an increase in the level of uric acid concentration in the blood serum, the doses of uricosuric anti-gout drugs should be adjusted. In the process of therapy, it is necessary to ensure the consumption of a sufficient amount of fluid and increased urine output for the excretion of uric acid.

The procedure for using the drug should be carried out in compliance with generally accepted sterility measures when preparing and diluting injection solutions by specially trained medical personnel. After the procedure, used syringes, needles, vials, ampoules and the remains of an unused drug must be disposed of.

Influence on the ability to drive vehicles and complex mechanisms

When using Doxorubicin, nausea, vomiting and other adverse reactions may occur, therefore, during treatment, care should be taken when driving or working with complex mechanisms that require increased concentration. If you experience any unwanted symptoms, you must refuse to participate in the above activities.

Drug interactions

The active substance of Doxorubicin is highly active, therefore only an oncologist can take into account its interaction with simultaneously taken drugs.

Analogs

Doxorubicin analogs are: Adriblastin fast-dissolving, Doxorubicin-Ronts, Doxorubicin-Ferein, Doxorubicin-Deco, Doxorubicin-Teva, Doxorubicin-Ebeve, Doxorubicin Lahema, Doxolek, Kelix, Onkodox 50.

Terms and conditions of storage

Keep out of the reach of children.

Store in a dark place at a temperature: lyophilisate - no higher than 5 ° C, concentrate - 2-8 ° C, do not freeze.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Doxorubicin

Many reviews of Doxorubicin contain references to serious side effects of the drug, which include feeling unwell for a long period of time, ulcerative skin lesions at the injection sites, hair loss, and negative effects on internal organs. Only a qualified doctor can assess the effectiveness of the drug in each specific case, who must take into account the patient's condition, the possible consequences of therapy, the type of cancer, the use of the drug as monotherapy or as part of a combination therapy, etc.

Doxorubicin price in pharmacies

The average price for doxorubicin in the form of a lyophilisate for the preparation of a solution for intravascular and intravesical administration is 231 rubles (per 1 bottle). The cost of a concentrate for preparing a solution for intravascular and intravesical administration varies from 229 to 273 rubles (the package includes 1 bottle of 5 ml) or from 520 to 750 rubles (for 1 bottle of 25 ml).

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!