The partially metabolized in the liver to form the active metabolite ol, to a lesser extent to form an aglycone binds glucuronide and sulfate. Enzymatic recovery under the action of oxidases, reductases and dehydrogenases results in the formation of free radicals that can contribute to the winstrol dosage manifestation of cardiotoxicity. The half – 20-48 hours for the and ol.
Clearance from plasma drug varies from 8 to 20 ml / min / kg. The clearance of is carried out mainly by metabolism and biliary excretion.
Excretion: in bile – 40% unchanged for 7 days, the kidneys 5 – 12% of and its metabolites for 5 days. Systemic clearance of is significantly reduced in women with obesity, the body mass of more than 130% of the optimum.
Children. The clearance of in children older than 2 years higher than that of adults, in children younger than 2 years of approaching the values of clearance in adults.
Elderly patients. Dose adjustment for age is required.
Paul. The average clearance of in men is significantly higher than in women. However, the half-life of in men – longer than females (54 and 35 hours, respectively).
Race. The effect of race on the pharmacokinetics of has not been studied.
Abnormal liver function. In patients with impaired liver function and clearance of is reduced ol.
Impaired renal function. Renal dysfunction does not require dose adjustment.
Indications for use
of breast cancer, lung cancer (small cell lung), mesothelioma, esophageal cancer, stomach cancer, primary hepatocellular carcinoma, pancreatic cancer, insulinoma, carcinoid, malignant tumors of the head and neck, thyroid cancer, malignant thymoma, ovarian cancer, germ cell testicular tumors, trophoblastic tumor, prostate cancer, bladder cancer (treatment and prevention of recurrence winstrol dosage after surgery), endometrial cancer, cervical cancer, uterine sarcoma, soft tissue sarcoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma, neuroblastoma, Wilms’ tumor, Kaposi’s sarcoma, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, Hodgkin’s disease and non-Hodgkin’s lymphoma, multiple myeloma.
Contraindications for use
- Increased sensitivity to or other ingredients, and also to other anthracyclines and anthracenediones.
- Pregnancy and lactation.
- Intravenous injection is contraindicated in: severe myelosuppression (neutrophil count less than 1500 cells / mm3), severe hepatic insufficiency, severe heart failure and arrhythmias, recent myocardial infarction, previous therapy with other anthracyclines and anthracenediones to limit cumulative doses, acute viral infections (including chickenpox, herpes zoster).
- Introduction into the bladder at contraindicated: invasive tumors with invasion into the bladder wall, urinary tract infections, inflammatory diseases of the bladder.
Caution should be used in patients previously treated with intensive chemotherapy; with heart disease; with risk factors for cardiotoxicity; Obesity, with tumor infiltration of bone marrow, with severe hepatic impairment (may require reduction in the starting dose or increase the interval between doses); urate nephrolithiasis (including history); in combined anticancer therapy, as well as in combination with radiation therapy or another anti-tumor; pediatric, elderly patients.
Pregnancy and lactation
Controlled trials of in pregnant women have been conducted. Animal studies have shown embryotoxic, teratogenic and mutagenic effects of . Therefore, should not be applied to pregnant women, .
Because passes into breast milk, in order to avoid the toxic effect of the drug on the baby during the period of treatment should stop breastfeeding.
Dosage and administration
intravenously, intraarterially or intravesically.
can be used both as monotherapy and in combination with other cytostatic at different doses depending on the regimen. At individual dose selection should be guided by the data of literature.
- as monotherapy recommended dose per cycle is 60-75 mg / m 2 every three weeks. Typically, the drug is injected once during the cycle; however, the cyclic dosage may be divided into multiple administrations (e.g., administered for three consecutive days the first or the first and eighth day of the cycle). The cycles are repeated every 3-4 weeks;
- to reduce the toxic effects, especially on the heart, used for a weekly regimen of 10-20mg / m of the preparation;
- in combination with other winstrol dosage anticancer drugs administered in a dose cyclic 30-60 mg / m 2 every 3-4 weeks.
. Abnormal liver function in patients with hyperbilirubinemia dose should be reduced according to the concentration of total bilirubin in serum:
- 50% reduction of the recommended doses of bilirubin in serum concentration 1.2-3.0 mg / dl;
- 75% reduction of the recommended doses of bilirubin in serum concentration above 3.0 mg / dL.
The total dose of should not exceed 550 mg / m 2 . In patients previously treated with radiation therapy to the area of the lungs and mediastinum, or treated with other cardiotoxic drugs, cumulative dose should not exceed 400 mg / m 2 .
Introduction into the bladder
Introduction into the bladder is used for the treatment of superficial bladder cancer and the prevention of recurrence after transurethral resection. Introduction into the bladder is not applicable for the treatment of invasive tumors with invasion into the muscle wall of the bladder.
The recommended dose for intravesical administration – 30-50 mg per instillation (drip), with intervals between doses from 1 week to 1 month, depending on the goals of therapy – treatment or prevention. The recommended concentration of the solution – 1 mg / ml of water for injection or 0.9% sodium chloride solution. After the instillation to ensure uniform exposure of the drug on the mucosa of the bladder, patients should turn from side to side every fifteen minutes. Typically, the drug must be in the bladder for 1-2 hours. After instillation, the patient should empty the bladder.
To avoid excessive dilution of the drug in urine, patients should be warned that they should refrain from taking fluids for 12 hours prior to instillation. Systemic absorption of to instillation into the bladder is very low.
When the local manifestations of toxic action (chemical cystitis, which may occur dysuria, polyuria, nocturia, painful urination, hematuria, discomfort in the bladder, necrosis of the bladder wall) dose intended for instillation should be dissolved in 50-100 ml of 0.9 % sodium chloride solution. Particular attention should be paid to issues related to catheterization (eg, when the urethral obstruction due to massive intravesical tumors).
Patients with hepatocellular carcinoma for intensive local effects while reducing the overall toxic effects of can be administered intraarterially in the main hepatic artery at a dose of 30-150 mg / m2 with an interval of 3 weeks to 3 months. Higher doses should be applied only in cases where simultaneously performed in vitro drug elimination. Because this method is potentially dangerous, and when you use it can happen air embolism and / or arterial thrombosis, leading to widespread necrosis of the tissue, intra-arterial administration may only doctors fluent in this methodology.