Description
Latin name
FARMORUBICIN ® RAPID DISSOLUTION
Release form
Lyophilisate for solution for intravascular and intravesical administration.
Packing
In a bottle of 50 mg of lyophilisate. In a cardboard box 1 bottle.
Pharmacological action
Pharmacodynamics
Antitumor drug from the group of synthetic anthracycline antibiotics. It quickly penetrates into cells, localized mainly in the nucleus. At the molecular level, epirubicin can complex with DNA by intercalation between major nucleotide pairs, which leads to a violation of the synthesis of DNA, RNA and proteins. Intercalation in DNA is the trigger for the cleavage of DNA under the action of topoisomerase II, leading to serious violations in the tertiary structure of DNA. Epirubicin (like doxorubicin) can be involved in oxidation / reduction reactions with the formation of highly active and highly toxic free radicals.
Pharmacokinetics
Distribution of
After iv administration, epirubicin is rapidly distributed in the body tissues and does not penetrate the BBB in detectable amounts.
Metabolism
Epirubicin is intensively biotransformed, mainly in the liver. The main established metabolites are epirubicinol, which has a certain degree of antitumor activity, as well as glucuronides of epirubicin and epirubicinol. 4′ -0- glucuronidation distinguishes epirubicin from doxorubicin and may result in less toxicity.
Excretion of
After iv administration of the drug (at a dose of 60-150 mg / m2) to patients with normal liver and kidney function, epirubicin levels decrease three-exponentially with a slow final phase lasting 30-40 hours. T1 / 2 of epirubicinol corresponds to that of epirubicin. Epirubicin is excreted mainly through the liver: about 38% of the administered dose is detected within 24 hours in bile in the form of epirubicin (19%), epirubicinol and other metabolites. 9-12% of the dose is excreted in the urine (both in the form of metabolites and in unchanged form). After 72 hours, approximately 43% of the administered dose is determined in bile and approximately 16% in urine.
Indications
Transitional cell carcinoma of the bladder
breast cancer
cancer of the stomach and esophagus
cancer of the head and neck
primary hepatocellular cancer
acute leukemia
non-small cell lung cancer small cell lung cancer small cell lung cancer pancreatic cancer
prostate cancer
colorectal cancer
sarcoma soft tissue
osteosarcoma.
Contraindications
Hypersensitivity to the drug and other anthracyclines or anthracendins
pregnancy
lactation (breastfeeding).
For iv administration:
Severe myelosuppression
severe hepatic dysfunction
severe heart failure
arrhythmias
recent myocardial infarction
previous treatment with cumulative doses of anthracyclines or anthracendion.
For insertion into the bladder:
Invasive tumor with penetration into the wall of the bladder
urinary tract infection
inflammation of the bladder.
Use during pregnancy and lactation
The drug is contraindicated in pregnancy and lactation.
Composition
1 vial contains:
Active substances: epirubicin hydrochloride 50 mg, which corresponds to an epirubicin content of 46.8 mg.
Excipients: methyl parahydroxybenzoate, anhydrous lactose.
Dosage and administration
The drug is used both as monotherapy and in combination with other cytostatics in various doses, depending on the treatment regimen. For individual dose selection should be guided by the data of the specialized literature.
With iv administration as monotherapy, the recommended standard dose per cycle for adults is 60-90 mg / m2 every 3-4 weeks. The total dose per cycle can be administered both simultaneously and divided into several injections for 2-3 days in a row.
If the drug is used in combination with other antitumor drugs, the recommended dose per cycle should be accordingly reduced.
In some cases, the drug can be used in higher doses of 90-120 mg / m2 once with an interval of 3-4 weeks.
Repeated injections of the drug are possible only with the disappearance of all signs of toxicity (especially hematological and gastrointestinal tract).
Patients with impaired renal function and a serum creatinine level of more than 5 mg / dl should be prescribed the drug in reduced doses.
In patients with impaired liver function, if the serum bilirubin concentration is 1, 2-3 mg / dl or AST value is 2-4 times higher than the upper limit of the norm, the administered dose should be reduced by 50% of the recommended. If the serum bilirubin concentration is more than 3 mg / dl or the AST value is more than 4 times higher than the VGN, the dose should be reduced by 75% of the recommended.
Patients who have previously received massive antitumor therapy, as well as with tumor bone marrow infiltration, are advised to prescribe the drug in lower doses or increase the interval between cycles.
In elderly patients, initial doses and regimens may be used during initial therapy.
To reduce the risk of thrombosis and extravasation, Pharmorubicin is recommended to be administered through the tube of an intravenous infusion system during drip 0. 9% sodium chloride solution or 5% glucose solution. The duration of the infusion should be from 3 to 20 minutes, depending on the dose of the drug and the volume of the infusion solution.
For the treatment of superficial bladder tumors, it is recommended to carry out 8 weekly instillations of the drug into the bladder at a dose of 50 mg (dissolved in 25-50 ml of physiological saline). When symptoms of local toxic effects appear (chemical cystitis, manifested by dysuria, polyuria, nocturia, painful urination, hematuria, discomfort in the bladder, necrosis of the bladder wall), the dose should be reduced to 30 mg.
When treating in situ bladder cancer, the dose may be increased to 80 mg depending on individual tolerance.
For the prevention of relapse after transurethral resection of superficial tumors, it is recommended to perform 4 weekly instillations of 50 mg followed by 11 monthly instillations in the same dose.
Instant pharmorubicin should be instilled through a catheter and left inside the bladder for 1 hour. During instillation, the patient should turn over to ensure uniform exposure of the solution to the mucous membrane of the bladder. In order to prevent excessive dilution of the drug with 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.
Particular attention should be paid to problems associated with catheterization (including with urethra obstruction, due to massive intravesical tumors).
In case of hepatocellular cancer, to provide an intensive local effect and at the same time reduce the general toxic effect, Pharmorubicin can be injected intraarterially into the main hepatic artery in a dose of 60-90 mg / m2 with an interval of 3 weeks to 3 months or in doses of 40-60 mg / m2 with an interval of 4 weeks.
Side effects
From the hematopoietic system: leukopenia, neutropenia (usually transient in nature, reaching the lowest level 10-14 days after drug administration, restoration of the blood picture is usually observed by 21 days), thrombocytopenia, anemia.
From the cardiovascular system: manifestations of early (acute) cardiotoxicity – sinus tachycardia and / or ECG abnormalities (nonspecific changes in the ST segment and T wave), possibly – tachyarrhythmias, including ventricular extrasystole and ventricular tachycardia, as well as bradycardia, AV- blockade, blockade of the legs of the bundle of His (these phenomena are not always a prognostic factor in the subsequent development of delayed cardiotoxicity, are rarely clinically significant and usually do not require discontinuation of drug therapy). The manifestations of late (delayed) cardiotoxicity include a decrease in the ejection fraction of the left ventricle and / or the development of symptoms of congestive heart failure, such as shortness of breath, pulmonary edema, orthostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion, gallop rhythm. Pericarditis, myocarditis are possible. The most severe form of cardiomyopathy caused by anthracyclines is life-threatening congestive heart failure, which limits the cumulative dose of the drug. Thromboembolic complications are possible, including pulmonary embolism (in some cases, fatal). digestive system: anorexia, stomatitis, nausea, vomiting, hyperpigmentation of the oral mucosa, esophagitis, pain or burning sensation in the abdomen, stomach erosion, gastrointestinal bleeding, colitis, diarrhea, increased liver transaminases and bilirubin levels in the blood serum .
From the urinary system: staining of urine in red within 1-2 days after administration of the drug may cause hyperuricemia.
From the side of the organ of vision: conjunctivitis, keratitis.
From the endocrine system: amenorrhea (usually ovulation is restored at the end of treatment, but premature menopause may develop) oligospermia, azoospermia (in some cases, the number of sperm is restored to normal levels, this can occur several years after the end of treatment) hot flashes.
Dermatological reactions: alopecia, rash, itching, sudden redness of the skin, hyperpigmentation of the skin and nails, photosensitivity, hypersensitivity to previously exposed skin.
Other: malaise, asthenia, fever, chills, anaphylactic reactions, acute lymphocytic leukemia, myelogenous leukemia.
Local reactions: erythematous striation along the vein into which the infusion was carried out, then local phlebitis or thrombophlebitis phlebosclerosis may occur, especially when reintroduced into a small vein. If the drug enters the surrounding tissues, local soreness, severe cellulitis, tissue necrosis may occur.
Side effects possible with intra-arterial administration: in addition to systemic toxicity – a stomach ulcer and duodenal ulcer (probably due to reflux into the gastric artery), narrowing of the bile ducts due to sclerosing cholangitis caused by the drug.
Drug Interaction
When co-administered, Formorubicin is rapidly soluble and may increase the toxicity of other antitumor drugs, especially the myelotoxic and gastrointestinal effects.
When concurrent use of Formorubicin soluble with other potentially cardiotoxic or cardioactive drugs (calcium channel blockers), cardiac activity should be monitored throughout the treatment period.
When used together, cimetidine increases the half-life of epirubicin (this combination is not recommended).
Pharmaceutical Interaction
Formorubicin should not be mixed with other medicines.
Formorubicin is not allowed to contact with solutions having an alkaline reaction, since this can lead to hydrolysis of epirubicin.
Formorubicin soluble should not be mixed with heparin because of their chemical incompatibility, which creates a precipitate.
overdose
Symptoms: severe myelosuppression (mainly leukopenia and thrombocytopenia), toxic manifestations of gastrointestinal tract (mucositis), acute complications from the heart.
Treatment: carry out symptomatic therapy. The antidote to epirubicin is unknown.
Storage conditions
Keep out of the reach of children at room temperature (15 ° to 25 ° C).
Expiration
4 years.
Active ingredient
Epirubicin
Terms of delivery from pharmacies
Prescription
Dosage
Dosage srd lkp infusion solution
