Description
Latin name
VERO-EPIRUBICIN
Release form
Lyophilisate for solution for iv administration.
Packing
1 pc
Indications
Breast cancer
cancer of the stomach and esophagus
pancreatic cancer
colorectal cancer
non-small cell and small cell lung cancer
senile and malignant cell carcinoma cancer
non-Hodgkin’s lymphoma
Hodgkin’s disease
hormone-resistant prostate cancer
multiple myeloma
acute leukemia.
Contraindications
Hypersensitivity to epirubicin or other components of the drug, as well as to other anthracyclines and anthracendins
pregnancy and lactation.
Intravenous administration is contraindicated in cases of persistent myelosuppression, severe liver dysfunction, severe heart failure and severe arrhythmias, recent myocardial infarction, prior therapy with epirubicin and / or other anthracyclines and anthracendion in total doses.
Introduction to the bladder is contraindicated in case of urinary tract infections, inflammation of the bladder, hematuria, invasive tumors with penetration into the bladder wall.
Caution: patients with risk factors for cardiotoxicity, patients who have previously received intensive chemotherapy, patients with tumor bone marrow infiltration, as well as patients with impaired liver and kidney function (it may be necessary to reduce starting doses or increase the interval between doses) as part of combined antitumor therapy, as well as in combination with radiation or other antitumor therapy. Safety and efficacy in children is not well understood. Cardiotoxicity in pediatric patients may be increased.
Use during pregnancy and lactation
The drug is contraindicated for use during pregnancy and lactation (breastfeeding).
Composition
1 vial contains:
Active substances:
epirubicin hydrochloride 10 mg.
Excipients:
mannitol,
methylhydroxybenzoate.
Dosage and administration of
Intravenously, intraarterially, intravesically.
Vero-epirubicin can be used both in monotheralia and in combination with other anticancer drugs, and therefore, when choosing the dose and regimen of the drug should be guided by the data of the literature.
Intravenous administration of
As a monotherapy, the recommended standard dose per cycle is 60-90 mg / m2 every three to four 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 Vero-Epirubicin is used in combination with other anticancer drugs, the recommended dose per cycle should be accordingly reduced. In some cases, high doses of Vero-epirubicin 90-120 mg / m2 can be used 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).
Impaired renal function. In patients with severe renal impairment (serum creatinine> 5 mg / dL), lower doses of Vero-epirubicin should be used.
Impaired liver function: If the serum bilirubin level is 1.2 3 mg / dl or the ACT value is 2 4 times higher than the upper limit of normal, the administered dose of Vero-epirubicin should be reduced by 50% of the recommended value. If the level of bilirubin in the blood serum exceeds 3 mg / dl or the ACT value is more than 4 times the upper limit of the norm, then the administered dose should be reduced by 75% of the recommended.
Other special patient groups. It is recommended to prescribe lower doses or increase the intervals between cycles in patients who previously received massive antitumor therapy, as well as in patients with tumor bone marrow infiltration.
In elderly patients, standard doses and regimens can be used during initial therapy.
Introduction to the bladder
To prevent relapse after transurethral resection of superficial bladder tumors, a single installation of 80-100 mg of Vero-epirubicin immediately after transurethral resection or eight weekly installations of 50 mg of Vero-epirubicin (25-50 ml 0.9 % sodium chloride solution), starting 2-7 days after transurethral resection. In case of development of local toxicity (chemical cystitis), the dose should be reduced to 30 mg. It is possible to carry out 4 weekly installations of 50 mg and then 11 monthly installations in the same dose.
Installation is carried out using a catheter, while the drug should remain in the bladder for 1 hour. To ensure uniform effect of the drug on the mucous membrane of the bladder, the patient should turn from side to side during installation. In order to avoid excessive dilution of the drug with urine, patients should be warned that they should refrain from taking fluid for 12 hours before installation. At the end of instillations, the patient should empty the bladder.
Intraarterial administration of
In patients with hepatocellular cancer, the drug can be administered as an infusion into the main hepatic artery at a dose of 60-90 mg / m2 with an interval of 3 weeks to 3 months or at a dose of 40-60 mg / m2 with an interval of 4 weeks.
Rules for the preparation and administration of
solution Vero-epirubicin should be dissolved in water for injection to a concentration of at least 2 mg / ml. After adding water for injection, the vial is shaken until the drug is completely dissolved. The prepared solution is stable for 24 hours at room temperature and for 48 hours at a temperature of from 4 to 10 ° C. The solution is stored in a dark place.
To reduce the risk of thrombosis and extravasation, Vero-epirubicin is recommended to be administered slowly (from 3 to 20 minutes, depending on the dose of the drug and the volume of the infusion solution) through the tube of the intravenous infusion system, during the infusion of 0.9% sodium chloride solution or 5 % dextrose solution.
Side effects
From the hemopoietic system: leukopenia, neutropenia, anemia, thrombocytopenia.
From the cardiovascular system: manifestations of early (acute) cardiotoxicity of epirubicin are mainly sinus tachycardia and / or ECG abnormalities (non-specific ST-T wave changes). Tachyarrhythmias (including ventricular extrasystole and ventricular tachycardia), bradycardia, AV block, and bundle branch block may also be noted. These effects are not always a prognostic factor for the development of subsequently delayed cardiotoxicity, are rarely clinically significant, and usually do not require discontinuation of drug therapy.
Late (delayed) cardiotoxicity is manifested by a decrease in the ejection fraction of the left ventricle (LVEF) and / or symptoms of congestive heart failure (CHF), such as shortness of breath, pulmonary edema, orthostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, exudative pleurisy. Subacute events may also occur, such as pericarditis / myocarditis. The most severe form of cardiomyopathy caused by anthracyclines is life-threatening CHF, which is toxicity that limits the cumulative dose of the drug.
In addition, thromboembolic complications, including pulmonary embolism (in some cases fatal), hot flashes can be observed.
From the digestive system: anorexia, nausea, vomiting, stomatitis, hyperpigmentation of the oral mucosa, esophagitis, pain or burning sensation in the abdomen, stomach erosion, gastrointestinal bleeding, diarrhea, colitis, increased levels of total bilirubin and serum transaminases.
From the urinary system: urine staining red for 1-2 days after the administration of Vero-epirubicin. Hyperuricemia may occur due to rapid lysis of tumor cells.
From the side of the organs of vision: conjunctivitis, keratitis.
From the side of the skin and skin appendages: alopecia, rash, itching, sudden redness of the skin, hyperpigmentation of the skin and nails, photosensitivity, hypersensitivity to irritated skin (anamnestic reaction to radiation), urticaria.
From the endocrine system: amenorrhea (at the end of therapy, ovulation is restored, but premature menopause can occur) oligospermia, azoospermia (in some cases, the number of sperm is restored to normal, this can occur several years after the end of therapy).
Local reactions. Often revealed erythematous striation along the vein into which the infusion was made, then local phlebitis or thrombophlebitis may occur. Phlebosclerosis can also develop, especially if Vero-epirubicin is reintroduced into a small vein. If the drug enters the surrounding tissues, local soreness, severe inflammation of the subcutaneous tissue and tissue necrosis may occur.
In case of intraarterial administration, in addition to systemic toxicity, ulceration of the stomach and duodenum (possibly due to reflux of the drug into the gastric artery) and narrowing of the bile ducts due to sclerosing cholangitis caused by the drug, as well as widespread necrosis of perfused tissue, can be observed.
Intravesical use of epirubicin can lead to symptoms of chemical cystitis (dysuria, polyuria, nocturia, painful urination, hematuria, discomfort in the bladder, necrosis of the wall of the bladder) and constriction of the bladder.
Other: malaise, asthenia, fever, chills, secondary infections, anaphylaxis, dehydration, the development of acute lymphocytic leukemia or myeloid leukemia.
Drug Interaction
Epinephrine, pilocarpine, systemic beta-blockers enhance action.
It is not recommended to bury two different beta blockers simultaneously.
Concurrent administration with eye drops containing epinephrine may result in mydriasis.
Increases the effect of muscle relaxants and general anesthetics (48 hours before general anesthesia, including the use of peripheral muscle relaxants, need to stop taking the drug).
Against the background of drug treatment, intravenous administration of verapamil, diltiazem should be avoided (suppression of AV conduction, development of bradycardia, and reduction of blood pressure may occur).
Use with caution with antihypertensive drugs, other beta-blockers, insulin or oral hypoglycemic drugs, glucocorticosteroids, psychoactive drugs, and drugs that have eradication associated with enhancement.
CYPIID6 inhibitors (including quinidine, cimetidine) can increase plasma concentrations of timolol, increasing the risk of developing systemic side effects of beta-blockers (including decreased heart rate, depression).by means of. In this regard, additive toxicity is possible, especially with regard to hematopoiesis and gastrointestinal tract.
Myelotoxic drugs increase the hematotoxicity of the drug.
When using epirubicin in combination with other potentially cardiotoxic chemotherapeutic agents, as well as with cardiovascular drugs (eg, slow calcium channel blockers), cardiac function should be monitored.
Epirubicin is actively metabolized in the liver. Changes in liver function caused by concomitant therapy may affect metabolism, pharmacokinetics, therapeutic efficacy, and / or toxicity of epirubicin.
Cimetidine causes a 50% increase in area under the concentration-time curve (AUC) of epirubicin, therefore, it should be discontinued before treatment with epirubicin.
Administration of paclitaxel to epirubicin may lead to increased plasma concentrations of unchanged epirubicin and its metabolites. No changes in the pharmacokinetics of epirubicin were observed with taxanes (paclitaxel or docetaxel) after epirubicin.
Epirubicin cannot be mixed with other drugs. Contact with alkaline solutions should be avoided as this may lead to hydrolysis of epirubicin. Due to the chemical incompatibility, epirubicin cannot be mixed with heparin (a precipitate forms when mixed).
Overdose
Acute overdose of epirubicin can lead to severe myelosuppression (mainly leukopenia and thrombocytopenia), toxic effects from the gastrointestinal tract (mainly mucositis), cause acute complications of the heart.
The antidote to epirubicin is unknown. In case of overdose, symptomatic therapy is recommended.
Storage conditions
Store in a dry place at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Expiration
2 years.
Active ingredient
Epirubicin
drugstore terms and conditions Prescription
dosage form
dosage form and
injection and infusion
