EPIRUBICIN-EBEVE 0.002/ML BOTTLE 50ML

Indications

- mammary cancer;

- ovarian cancer;

- non-small cell and small cell lung cancer;

- cancer of the stomach and esophagus;

- primary hepatocellular carcinoma;

- transitional cell carcinoma of the bladder;

- soft tissue sarcoma;

- osteosarcoma;

- non-Hodgkin's lymphoma;

- Hodgkin's disease;

- acute leukemia;

- multiple myeloma;

- pancreas cancer;

- rectal cancer;

- head and neck cancer.

Epirubicin can be used both as monotherapy and in combination with other cytotoxic drugs in various doses, depending on the regimen of therapy. When individual dose should be guided by the data of special literature.

Intravenous administration

As a monotherapy, the recommended standard dose per cycle for adults makes 60-90 mg / m2 every 3-4 weeks. The total dose of the drug per cycle can be administered both simultaneously, and divided into several injections, for 2-3 days in a row.

If epirubicin is used in combination with other anticancer drugs, the recommended dose per cycle should be reduced accordingly.

In some cases, high doses of epirubicin 90-120 mg / m can be used.2 once with an interval of 3-4 weeks.

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

Have patients with severe impaired renal function (serum creatinine> 5 mg / dL) lower doses of Epirubicin-Ebeve should be used.

Have patients with impaired liver function when the content of bilirubin in the serum is in the range of 1.2-3 mg / dL or the level of ACT is 2-4 times higher than VGN, the administered dose of epirubicin should be reduced by 50% from the recommended; when the content of bilirubin in the serum is more than 3 mg / dL or the level of ACT is more than 4 times higher than VGN, the dose should be reduced by 75% from the recommended.

It is recommended the appointment of the drug in lower doses or an increase in the intervals between cycles in patients who have previously received massive antitumor therapyas well as patients with tumor infiltration of the bone marrow.

Have elderly patients during initial therapy, standard doses and regimens can be used.

To reduce the risk of thrombosis and extravasation, it is recommended to inject epirubicin through the tube of the system for intravenous infusion, during the infusion of a 0.9% solution of sodium chloride or 5% of dextrose. Duration of infusion should be from 3 to 20 minutes depending on the dose of the drug and the volume of the infusion solution.

Introduction to the bladder

For treatment superficial bladder tumors It is recommended to conduct 8 weekly instillations of 50 mg each (in 25-50 ml of 0.9% sodium chloride solution). If symptoms of local toxicity (chemical cystitis) appear, the dose should be reduced to 30 mg.

In the treatment of in situ bladder cancer, depending on the individual tolerance, the dose of the drug can be increased to 80 mg.

For prevention of recurrence after transurethral resection of superficial tumors 4 weekly instillations of 50 mg each are recommended followed by 11 monthly instillations at the same dose.

Epirubicin is injected into the bladder through a catheter and left inside the bladder for 1 hour. During the instillation, the patient must roll from side to side to ensure a uniform effect of the solution on the bladder mucosa. To prevent excessive dilution of the drug in the urine, the patient should be warned about the need to refrain from drinking for 12 hours before instillation. At the end of the instillation procedure, the patient should empty the bladder.

Special care should be taken when bladder catheterization occurs in patients with urethral obstruction caused by massive intravesical tumors.

Intraarterial administration

Patients with hepatocellular carcinoma to provide intensive local exposure while reducing the overall toxic effect of Epirubicin-Ebeve can be introduced into the main hepatic artery at a dose of 60-90 mg / m2 with an interval from 3 weeks to 3 months or at a dose of 40-60 mg / m2 with an interval of 4 weeks.

From the hemopoietic system: leukopenia, neutropenia. Cytopenia usually reaches its lowest value in 10-14 days after drug administration, recovery of the blood picture is usually observed on day 21. Thrombocytopenny and anemia are also possible.

Since the cardiovascular system: manifestations early (acute) The cardiotoxicity of epirubicin is mainly sinus tachycardia and / or abnormalities on the ECG (non-specific changes in ST-T waves). Tachyarrhythmias can also occur, including ventricular premature beats and ventricular tachycardia, as well as bradycardia, AV block and His blockade. The occurrence of these phenomena is not always a prognostic factor for the development of subsequently delayed cardiotoxicity, they are rarely clinically significant and usually do not require discontinuation of epirubicin therapy. Late (delayed) cardiomyopathy is manifested by a decrease in the left ventricular ejection fraction and / or symptoms of chronic heart failure, such as shortness of breath, pulmonary edema, orthostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, exudative pleurisy, and gallop rhythm. Subacute events such as pericarditis / myocarditis may also occur. The most severe form of cardiomyopathy caused by anthracyclines is life-threatening heart failure, which is toxicity that limits the total dose of the drug.

From the digestive system: anorexia, nausea, vomiting, stomatitis, hyperpigmentation of the oral mucosa, esophagitis, pain or a burning sensation in the abdomen, gastric erosion, Gastrointestinal bleeding, diarrhea, colitis, increased serum total bilirubin and liver transaminase activity.

From the urinary system: red staining of urine for 1-2 days after epirubicin administration. Perhaps the appearance of hyperuricemia.

From the organs of vision: conjunctivitis, keratitis.

On the part of the endocrine system: amenorrhea (after the end of therapy, ovulation is restored, however, premature menopause may occur), oligospermia, azoospermia (in some cases the number of spermatozoa is restored to normal levels; this can happen several years after the end of therapy), flushes of heat to the face.

Dermatological reactions: alopecia, rash, itching, sudden reddening of the skin, hyperpigmentation of the skin and nails, photosensitivity and hypersensitivity of the irradiated skin areas (anamnestic reaction to radiation).

From the blood coagulation system: thromboembolic complications, including pulmonary embolism (in some cases with a fatal outcome).

Local reactions: erythematous striation along the vein into which the infusion was performed, local phlebitis or thrombophlebitis, phlebosclerosis (more often with repeated injections into the veins of small diameter).In case of ingestion of the drug and the surrounding tissues - pain, pronounced cellulite and necrosis of the surrounding tissues.

When intra-arterial injection in addition to systemic toxicity, gastric and duodenal ulcers may be observed (probably due to the reflux of the drug in the gastric artery); narrowing of the bile duct due to drug-induced sclerosing cholangitis.

With the introduction of the bladder: the development of chemical cystitis (dysuria, polyuria, nocturia, painful urination, hematuria, discomfort in the bladder area), necrosis of the walls and wrinkling of the bladder.

Other: general malaise, asthenia, fever, chills, anaphylaxis, the addition of secondary infections, the development of secondary acute lymphocytic leukemia or myeloid leukemia.

- pregnancy;

- lactation period (breastfeeding);

- children's age (efficacy and safety have not been established);

- Hypersensitivity to epirubicin or other components of the drug, as well as to other anthracyclines or anthracene.

For intravenous

- severe myelosuppression;

- severe liver dysfunction;

- severe heart failure and arrhythmias;

- recent myocardial infarction;

- previous therapy with other anthracyclines or anthracenedions in limiting total doses.

For bladder injection

- invasive tumors with penetration into the bladder wall;

- urinary tract infection;

- inflammation of the bladder.

The prescription of the drug during pregnancy and lactation (breastfeeding) is contraindicated.

Men and women of childbearing agereceiving epirubicin therapy should use reliable contraceptive methods.

Epirubicin treatment should be carried out under the supervision of a physician with experience in the use of anticancer drugs.

To reduce the risk of toxic damage to the heart, it is recommended that, prior to and during epirubicin therapy, regular monitoring of its function, including evaluation of the left ventricular ejection fraction according to EchoCG or multichannel radioisotope angiography, and ECG monitoring. Early clinical diagnosis of heart failure due to the use of the drug is very important for its successful treatment.

Acute cardiotoxicity in most cases is transient (reversible) in nature, and is usually not considered as an indication for discontinuation of epirubicin therapy. Late (delayed) toxicity (cardiomyopathy) depends on the total dose, and therefore the recommended cumulative dose of epirubicin (900-1000 mg / m2), can be exceeded only in exceptional cases. Risk factors for cardiotoxicity include diseases of the cardiovascular system in the active stage or latent, previous or ongoing radiation therapy in the mediastinum / pericardial region,previous therapy with other anthracyclines or anthracenedions, as well as the simultaneous administration of other drugs that suppress the contractile function of the heart. Cardiotoxicity caused by epirubicin develops predominantly during treatment or within 2 months after its termination, however, delayed side effects may occur (several months or even years after the end of therapy).

When signs of chronic cardiotoxicity are found, treatment with epirubicin is immediately stopped.

In the process of treatment with epirubicin, especially when using high doses, it is necessary to evaluate hematological parameters (leukocyte count, platelet count, hemoglobin, blood corpuscles) and liver function tests before and during each cycle of therapy.

When the first signs of extravasation of epirubicin (burning or soreness at the injection site) appear, the infusion should be stopped immediately. The remaining dose should be injected into another vein. Locally carry out measures to eliminate the effects of extravasation. It is advisable to use ice packs.

When epirubicin is used, hyperuricemia may occur due to the rapid lysis of tumor cells, and therefore patients are advised to determine the level of uric acid, potassium, Calcium and creatinine in blood serum during therapy. Hydration, alkalization and prophylaxis with Allopurinol can minimize
risk of complications associated with tumor lysis syndrome.

When working with epirubicin, it is necessary to follow the rules for handling cytotoxic substances. It is recommended that the contaminated surface be treated with a dilute solution of sodium hypochlorite (containing 1% chlorine). In case of contact with the skin, immediately wash the skin with plenty of water with soap and water or sodium bicarbonate solution; in case of contact with eyes, delay the eyelids and rinse the eyes (eyes) with plenty of water for at least 15 minutes.

Symptoms: severe myelosuppression (mainly leukopenia and thrombocytopenia), toxic effects of the gastrointestinal tract (mainly mucositis), acute complications of the heart.

Treatment: antidote to epirubicin is not known; conduct symptomatic therapy.

Epirubicin can increase the toxicity of other anticancer drugs, especially myelotoxicity and toxic effects on the gastrointestinal tract.

When using epirubicin as part of combination Chemotherapy with other potentially cardiotoxic drugs, as well as when it is used simultaneously with other cardio-active drugs (for example, calcium channel blockers), it is necessary to monitor cardiac activity during the entire period of treatment.

Cimetidine increases T1/2 epirubicin, so at the time of treatment with Epirubicin it should be canceled.

The solution of Epirubicin-Ebeve cannot be mixed with other drugs, with alkaline solutions (hydrolysis of epirubicin is possible), with Heparin (a precipitate is formed).

List B. The drug should be stored in a dark place, out of the reach of children at a temperature of 2 ° to 8 ° C; do not freeze.