$21.30
Manufacturer: Austria
Treatment of a wide range of neoplastic diseases, including acute leukemia, lymphoma, malignant neoplasms in children and solid tumors in adults, in particular breast and lung carcinomas.
Description
Doxorubicin Amaxa Storage
active substance: doxorubicin;
1 ml of concentrate contains 2 mg of doxorubicin hydrochloride;
Doxorubicin Medak Excipients: sodium chloride, 0.1 M hydrochloric acid solution, water for injections.
Doxorubicin Amaxa Dosage form
Concentrate for solution for infusion.
Main physical and chemical properties: clear red solution.
Pharmacotherapeutic group
Antineoplastic and immunomodulatory agents. Cytotoxic antibiotics and related substances. ATX code L01D B01.
Pharmacological properties
Pharmacodynamics.
Is a cytotoxic anthracycline antibiotic isolated from a culture of Streptomyces peucetius var. caesius. Doxorubicin is now produced semi-synthetically from daunorubicin.
The exact mechanism of action has not been definitively elucidated. Doxorubicin is thought to exert its antitumor effect through cytotoxic mechanisms of action, especially by DNA intercalation, inhibition of the enzyme topoisomerase II, and the formation of reactive oxygen species (ROS). All of them have a detrimental effect on DNA synthesis: intercalation of the doxorubicin molecule leads to inhibition of RNA and DNA polymerase by disrupting the recognition of bases and sequence specificity. Inhibition of topoisomerase II causes single- and double-stranded breaks in the DNA helix. DNA cleavage also results from a chemical reaction with highly reactive oxygen species, such as the OH * hydroxyl radical, resulting in mutagenesis and chromosomal aberrations.
The specificity of doxorubicin toxicity is apparently primarily related to the proliferative activity of healthy tissue. Thus, the bone marrow, gastrointestinal tract and gonads are the main damaged normal tissues.
Doxorubicin Amaxa Pharmacokinetics.
Distribution
Following intravenous administration, doxorubicin is rapidly excreted from the blood and is widely distributed to tissues including the lungs, liver, heart, spleen, lymph nodes, bone marrow and kidneys. The volume of distribution is approximately 25 l / kg. The degree of binding to blood plasma proteins is 60-70%.
Doxorubicin does not cross the blood-brain barrier, although higher levels of the drug may be achieved in the presence of brain metastases or cerebral leukemia. Doxorubicin spreads rapidly to ascites, where it reaches higher concentrations than in plasma. Doxorubicin is excreted in breast milk.
Breeding
Elimination of doxorubicin from the blood is three-phase with half-lives of 12 minutes (distribution), 3.3 hours and 30 hours. Doxorubicin is rapidly metabolized in the liver. The major metabolite is the less active 13 dihydroderivative doxorubicinol. Other metabolites are deoxyrubicin aglycone, glucuronide and sulphate conjugate. Approximately 40-50 doses are excreted in the bile within 7 days, of which approximately half is excreted unchanged drug and the remainder as metabolites. Only 5-15% of the administered dose is excreted in the urine.
Special groups of patients
Because excretion of doxorubicin is mainly via the liver, hepatic dysfunction leads to delayed excretion and, consequently, to increased retention and accumulation in blood plasma and tissues.
Although renal excretion is a secondary route of excretion for doxorubicin, severe renal insufficiency may affect complete excretion.
In a study in overweight patients (> 130% of ideal body weight), doxorubicin clearance was reduced and the half-life was increased compared to the control group of normal weight patients.
Indication
Treatment of a wide range of neoplastic diseases, including acute leukemia, lymphoma, malignancies in children and solid tumors in adults, including breast and lung cancer.
Contraindication
Hypersensitivity to the active substance or to other components of the drug, other anthracyclines or anthracenediones. Pregnancy, breastfeeding.
When administered intravenously:
Persistent myelosuppression; severe liver dysfunction; severe myocardial dysfunction; unstable angina; recent myocardial infarction; severe arrhythmia; 4th degree heart failure; acute inflammatory cardiomyopathy; acute myocardial infarction; acute infection; severe stomatitis caused by previous treatment with cytotoxic agents and / or radiation (including in patients at high risk of bleeding); the presence of oral ulcers; prodromal symptoms may be a burning sensation, prolongation of treatment in the presence of this symptom is not a river
omendovano; acute development of heart failure; previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin and / or other anthracyclines and anthracendiones.
Recent Reviews