Syndroxocin
Sindroxocin: 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. Application during pregnancy and lactation
- 10. For violations of liver function
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Sindroxocin
ATX code: L01DB01
Active ingredient: doxorubicin (Doxorubicin)
Manufacturer: Sindan-Pharma S. K S.r. L. (Sindan-Pharma SCSRL) (Romania); Timurgan Pharmacy GmbH & Co. KG (Thymoorgan Pharmazie GmbH & Co. KG (Germany); Actavis Italy SpA (Italy)
Description and photo update: 2019-25-12
Sindroxocin is an antitumor antibacterial drug.
Release form and composition
The drug is released in the form of a lyophilisate for the preparation of a solution for intravesical and intravascular administration: a porous mass of red color (10 and 50 mg each in glass vials, instructions for use of Sindroxocin and 1 vial in a cardboard box).
The composition of the drug for 1 bottle:
- active substance: doxorubicin hydrochloride - 10 or 50 mg;
- auxiliary components: methyl parahydroxybenzoate, anhydrous lactose (in the form of lactose monohydrate).
Pharmacological properties
Pharmacodynamics
Sindroxocin is an anthracycline antibiotic with antitumor activity. Its active substance is isolated from the culture of Streptomyces peucetius var. caesius.
It has antimitotic and antiproliferative properties. The mechanism of action of Sindroxocin is based on its ability to interact with DNA, form free radicals, directly affect cell membranes and suppress the synthesis of nucleic acids.
Cells are sensitive to doxorubicin in the S and G2 phases.
Pharmacokinetics
After the administration of Sindroxocin, doxorubicin is rapidly absorbed and relatively evenly distributed throughout the body. Does not have the ability to penetrate the blood-brain barrier. About 75% of the administered dose binds to plasma proteins.
It is metabolized in the liver, as a result of biotransformation, the active metabolite doxorubicinol is formed. Under the action of reductases, oxidases and dehydrogenases, enzymatic reduction of doxorubicin occurs, this causes the formation of free radicals, which may lead to a manifestation of cardiotoxic action.
After intravenous (IV) administration, the drug quickly leaves the blood and is concentrated in the kidneys, liver, lungs, spleen and myocardium.
The half-life of doxorubicin and doxorubicinol is 20–48 hours.
It is excreted: 40% with bile in unchanged form within 7 days, 5-12% with urine in unchanged form and in the form of metabolites for 5 days.
Indications for use
- trophoblastic tumors;
- cancer of the stomach and esophagus;
- pancreas cancer;
- Wilms tumor (nephroblastoma);
- primary hepatocellular carcinoma;
- mesothelioma;
- small cell lung cancer;
- carcinoid;
- Kaposi's sarcoma;
- mammary cancer;
- ovarian cancer;
- cervical cancer;
- endometrial cancer;
- sarcoma of the uterus;
- germ cell tumors of the testicle;
- prostate cancer;
- insulinoma;
- acute myeloid / lymphoblastic leukemia;
- thyroid cancer;
- bladder cancer (including prevention of relapse after surgery);
- multiple myeloma;
- Hodgkin's disease and non-Hodgkin's lymphomas;
- sarcoma of soft tissues, including rhabdomyosarcoma;
- head and neck cancer;
- osteosarcoma;
- neuroblastoma;
- malignant thymoma;
- chronic lymphocytic leukemia;
- Ewing's sarcoma.
Contraindications
Absolute contraindications for all methods of drug administration:
- pregnancy and lactation;
- hypersensitivity to any component of Sindroxocin, other anthracyclines or anthracenediones.
Additional absolute contraindications to the introduction of the drug into the bladder:
- inflammation of the bladder;
- urinary tract infections;
- invasive tumors with penetration into the bladder wall.
Additional absolute contraindications for intravenous administration of Sindroxocin:
- herpes zoster;
- chicken pox;
- recent myocardial infarction;
- arrhythmias;
- severe heart failure;
- severe myelosuppression;
- severe liver failure;
- previous therapy with other anthracenediones or anthracyclines in limiting total doses.
Sindroxocin should be used with caution in patients with heart disease (at low total doses, the cardiotoxic effect of the drug may appear), hyperbilirubinemia, hepatic failure, gastric ulcer and duodenal ulcer, infiltration of tumor cells in the bone marrow, urate nephrolithiasis (including), in anamnesis and also after radiation or chemotherapy.
Sindroxocin, instructions for use: method and dosage
Syndroxocin is used as a monopreparation or as part of combination therapy in combination with cytostatics, the dose of which depends on the chosen treatment regimen.
Intravenous administration
With the i / v route of administration, the solution prepared from the lyophilisate of Sindroxocin is injected slowly (within 3-5 minutes) in a stream. Care should be taken to avoid extravasation and reduce the risk of thrombosis; the drug is recommended to be administered through the intravenous system tube during the infusion of 5% dextrose solution or 0.9% sodium chloride solution.
Recommended doses:
- monotherapy: 60-75 mg / m 2 every 3-4 weeks. If necessary, it is allowed to divide the total cyclic dose into several injections during the cycle (for example, in equal parts daily in the first 3 days or in equal parts on the first and eighth days of the cycle). In order to reduce the toxic effect of Sindroxocin (especially the cardiotoxic effect), it is possible to administer the solution daily at 10–20 mg / m 2;
- complex therapy: the cycle dose is 30-60 mg / m 2, the cycles are repeated at intervals of 3-4 weeks.
For patients with hyperbilirubinemia, the dose of Sindroxocin is reduced depending on the level of total bilirubin in the blood serum:
- bilirubin 12-30 mg / l: the dose of doxorubicin is reduced by 50%;
- bilirubin more than 30 mg / l: the doxorubicin dose is reduced by 75%.
Children, the elderly, obese people, patients with tumor infiltration of the bone marrow and patients who have previously received massive anticancer therapy should increase the intervals between cycles or reduce the dose of Sindroxocin.
The maximum total dose of Sindroxocin is 550 mg / m 2, and for patients who have previously received other cardiotoxic drugs or radiation therapy to the mediastinal and pulmonary area, 400 mg / m 2.
Intra-arterial administration
In hepatocellular cancer, a more intense local effect with a simultaneous decrease in toxic effect can be achieved by introducing Sindroxocin into the main hepatic artery.
The dose of the drug can be from 30 to 150 mg / m 2, the interval between injections is 3–12 weeks. At higher doses, doxorubicin is allowed to be used only if simultaneous extracorporeal elimination of the drug is ensured.
This method is potentially dangerous as there is a risk of developing advanced tissue necrosis. Intra-arterial administration can only be carried out by a doctor who is fluent in this technique.
Introduction to the bladder
With intravesical administration, the dose per instillation is 30-50 mg, the frequency of use of Sindroxocin is 1-4 weeks, depending on the purpose of therapy (treatment or prevention of relapse). The concentration of the solution is usually kept in the ratio of 1 ml of the drug to 1 ml of injection water or 0.9% sodium chloride solution. After administration, every 15 minutes for 1–2 hours, the patient should turn from side to side to ensure a uniform effect of doxorubicin on the bladder mucosa. Then the bladder must be emptied.
During the 12 hours preceding the instillation of Sindroxocin, the patient should restrict the intake of fluids in order to avoid excessive dilution of the drug in urine.
In the case of the development of a local toxic effect (expressed by chemical cystitis, which manifests itself as discomfort in the bladder area, painful urination, polyuria, hematuria, dysuria, nocturia, necrosis of the bladder wall), the dose intended for instillation is dissolved in 50-100 ml of sodium chloride solution 0, nine%. Special attention is paid to problems associated with catheterization (for example, in patients with urethral obstruction due to massive intravesical tumors).
Side effects
- from the immune system: flushing of the skin of the soles and palms, urticaria, dermatitis, skin rash, bronchospasm; rarely - anaphylaxis;
- from the urinary system: urine staining red (observed in the first 12 days after the administration of Sindroxocin);
- on the part of the cardiovascular system: sinus tachycardia and / or abnormalities on the electrocardiogram (nonspecific changes in ST – T waves) as manifestations of early acute cardiotoxicity of the drug; possible bradycardia, ventricular premature beats, tachyarrhythmias (including ventricular tachycardia), bundle branch block, atrioventricular blockade - these side effects rarely have clinical significance, therefore, Sindroxocin should not be discontinued. Subacute events such as myocarditis or pericarditis may occur. Symptoms of delayed (late) myocardial damage: decreased left ventricular ejection fraction without clinical manifestations and / or signs of congestive heart failure (peripheral edema, pulmonary edema, ascites, dyspnea, exudative pleurisy, hepatomegaly, cardiomegaly, gallop rhythm, oliguria). There is a risk of developing life-threatening congestive heart failure. Sometimes phlebitis, thrombophlebitis and thromboembolic complications occur, including pulmonary embolism (in some cases with a fatal outcome);
- on the part of the reproductive system: amenorrhea in women (ovulation is restored after the end of doxorubicin therapy, however, premature menopause is possible); oligospermia and azoospermia in men (in some patients, the sperm count is able to recover to normal, this can happen several years after the end of treatment);
- from the digestive system: abdominal pain, colitis, diarrhea, hyperpigmentation of the oral mucosa, stomatitis, nausea, vomiting, anorexia, bleeding from the gastrointestinal tract, esophagitis (in severe cases with ulceration of the mucous membranes of the digestive tract), increased activity hepatic enzymes and total serum bilirubin;
- on the part of the hematopoietic organs: dose-dependent reversible neutropenia and leukopenia (leukopenia of the lowest value usually reaches 10-14 days after administration of Sindroxocin, the blood picture is restored mainly on day 21), anemia, thrombocytopenia;
- from the senses: lacrimation, conjunctivitis, keratitis;
- on the part of the skin and skin appendages: complete alopecia (reversible, hair growth usually resumes 2-3 months after the discontinuation of Sindroxocin), pruritus, rash, urticaria, photosensitivity, hyperpigmentation of the skin and nails; in patients who have previously received radiation therapy in places corresponding to the radiation fields, in 4-7 days after the administration of doxorubicin, severe pain, edema, erythema with the formation of bubbles, hypersensitivity of irritated skin, moist epidermis are possible;
- local reactions: erythematous striation along the vein into which Sindroxocin was injected, with the further development of local phlebitis or thrombophlebitis, phlebosclerosis (especially in patients to whom Sindroxocin was injected repeatedly into a small vein); if doxorubicin enters the surrounding tissues, local soreness, serious inflammation of the subcutaneous tissue, and then tissue necrosis are possible;
- additional reactions due to intra-arterial administration: narrowing of the bile ducts due to sclerosing cholangitis caused by Sindroxocin, gastric and duodenal ulcers;
- additional reactions due to intravesical administration: cystitis;
- others: malaise, chills, fever, asthenia, hot flashes of the face, hyperuricemia or nephropathy due to increased production of uric acid, acute lymphocytic or myelocytic leukemia.
Overdose
Doxorubicin overdose is fraught with the development of severe myelosuppression (expressed mainly by thrombocytopenia and leukopenia), acute cardiotoxicity, and toxic effects from the digestive system.
No antidote has been established. Treatment of intoxication is symptomatic.
special instructions
Anticancer antibiotic therapy is carried out under the strict supervision of a physician with appropriate qualifications.
In order to reduce the likelihood of toxic damage to the heart, before the appointment of Sindroxocin and regularly during its use, the functions of the cardiac system should be monitored, including the assessment of the left ventricular ejection fraction by echocardiography or multichannel radioisotope angiography, as well as monitoring using an electrocardiogram. When heart failure develops on the background of doxorubicin therapy, early diagnosis is extremely important. Established chronic cardiotoxicity requires immediate discontinuation of Sindroxocin.
Acute cardiotoxicity is predominantly reversible and is usually not an indication for discontinuation of Sindroxocin. Delayed cardiomyopathy depends on the total dose of the drug. Functional disturbance infarction can occur with a probability of 12% when administered total dose of 300 mg / m 2, the risk increases slowly when applied dose of 450-550 mg / m 2, then with increasing doses significantly increases, and therefore is not recommended to exceed the total dose 550 mg / m 2.
Additional risk factors for the development of cardiotoxicity are: a history of heart disease, the simultaneous use of other drugs with a potential cardiotoxic effect (cyclophosphamide or 5-fluorouracil), previous radiation therapy in the mediastinal area, previous therapy with anthracyclines or anthracenedions, etc. In such patients, the development of toxic actions at lower total doses of Sindroxocin, therefore, monitoring of the function of the heart muscle should be especially careful.
Cardiotoxicity associated with the use of doxorubicin often occurs during a therapeutic course or within two months after its completion. However, there is a risk of developing delayed adverse reactions several months (and sometimes even years) after the completion of treatment.
Before the start of each cycle of drug treatment and periodically during its implementation, it is necessary to assess hematological parameters, including determining the number of blood corpuscles, platelets, leukocytes and hemoglobin, and conducting liver function tests.
If symptoms of extravasation appear during administration of the drug (pain or burning sensation at the injection site), the infusion should be stopped immediately. Until the full dose is received, Sindroxocin is continued in another vein. The effects of extravasation are dealt with by local activities, including the use of ice packs.
It is recommended to avoid, if possible, doxorubicin infusion into the veins above the joints and veins of the extremities with impaired lymphatic or venous drainage.
Rapid lysis of tumor cells can contribute to the development of hyperuricemia; therefore, it is necessary to control the concentration of uric acid, calcium, potassium, creatinine. To minimize the risk of complications associated with tumor lysis syndrome, measures to prevent hyperuricemia, such as prophylactic administration of allopurinol, increased hydration and alkalinization of urine, allow. Patients with hyperuricemia and gout, with an increase in uric acid concentration, may require dose adjustment of the anti-gout agent.
Careful observation is necessary in patients with developing neutropenia or leukopenia in order to detect signs of infection in time.
If there are no urgent indications for immunization, it is recommended to refrain from vaccination for the period from 3 to 12 months after using Sindroxocin. Family members of the patient who live together should not be immunized with the oral polio vaccine. The patient and his family members should avoid contact with persons who received this vaccine, or wear a protective mask that covers the mouth and nose.
Patients of reproductive age (both women and men) should use reliable methods of contraception for the entire period of treatment with Sindroxocin and at least for the next 3 months.
Medical personnel working with Sindroxocin must follow the rules for handling cytotoxic substances. If any surface is contaminated by the preparation, it should be treated with a dilute sodium hypochlorite solution (with 1% chlorine content). If the drug gets on the skin, immediately wash it with a large amount of sodium bicarbonate solution or soapy water; in case of contact with the eye, pull off the eyelid and rinse the eyes with plenty of water (at least 15 minutes).
Application during pregnancy and lactation
Syndroxocin is contraindicated in women during pregnancy and lactation.
For violations of liver function
In case of severe hepatic insufficiency, it is contraindicated to administer the drug intravenously.
With mild to moderate hepatic impairment, Sindroxocin should be used with caution.
Drug interactions
With the combined use of other anticancer drugs, it is possible to increase their toxicity, especially toxic effects on the digestive system and myelotoxicity.
Particular care should be taken with the concomitant administration of other cytotoxic agents with potential cardiotoxicity (such as cyclophosphamide, 5-fluorouracil). During the entire course of treatment, it is necessary to carefully monitor the functions of the heart.
Syndroxocin can increase hemorrhagic cystitis, which develops while taking cyclophosphamide, increase the hepatotoxicity of 6-mercaptopurine, enhance the toxic effect of radiation therapy on mucous membranes, liver, myocardium and skin.
The half-life of doxorubicin is increased with the simultaneous use of streptozotocin.
Syndroxocin enhances the replication of the virus given in the form of a viral vaccine and its side effects or decreases the production of antibodies in response to the vaccine.
When using uricosuric anti-gout drugs, the risk of developing nephropathy increases.
Hepatotoxic drugs can increase the toxicity of doxorubicin.
To avoid hydrolysis, Sindroxocin must not be mixed with any other medicinal products. Avoid contact with alkaline solutions.
Doxorubicin is pharmaceutically incompatible with 5-fluorouracil, sodium succinate, cephalothin, hydrocortisone, dexamethasone, heparin, aminophylline and other antineoplastic agents.
Analogs
Analogues of Sindroxocin are Fast-dissolving Adriblastin, Bleomycetin, Blenamax, Bleocin, Vero-Mitomycin, Vero-Epirubicin, Dactinomycin, Doxorubicin, Ixempra, Cosmegen, Kelix, Maltin, Rubida, Nicorubin, Rubomitsycin-Epirubicin, Fast
Terms and conditions of storage
Shelf life is 2 years.
Keep out of reach of children at temperatures up to 25 ° C.
The solution prepared from the lyophilisate is stable for 24 hours at a temperature of 25 ° C and for 48 hours at a temperature of 2–8 ° C. It is recommended to use it immediately after dilution, however, if necessary, it can be stored at a temperature of 2–8 ° С for no more than 24 hours.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Syndroxocin
As with other anticancer drugs with a similar active substance, there are practically no reviews of Sindroxocin, which is probably due to the severe specifics of its use.
Doxorubicin is most often used as part of complex therapy, so its effectiveness is difficult to assess. In addition, the type of oncological disease, the general condition of the patient, the presence of concomitant pathologies, etc. are of great importance. It is reliably known that Sindroxocin causes many side effects, including hair loss, the formation of ulcers at the injection sites, and damage to internal organs.
Price for Sindroxocin in pharmacies
The price of Sindroxocin 50 mg in the form of a lyophilisate for preparing a solution for intravesical and intravascular administration is 510–569 rubles. for 1 bottle.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, 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!
