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Active ingredients
Vinorelbine
Release form
Capsules
Composition
Vinorelbine tartrate (vinorelbine base) - 41.55 (30) mg. Additional substances: anhydrous ethanol; purified water; glycerol; macrogol 400 - qs Capsule capsule: gelatin, glycerin 85%, anidribsorb 85/70 (D-sorbitol and 1,4-sorbitan), medium chain triglycerides PHOSAL 53 MST (phosphatidylcholine, glycerides, ethanol), red oxide E172, iron yellow oxide E171 - qs
Pharmacological effect
Antitumor
Pharmacokinetics
After iv injection, plasma kinetics is a three-phase exponential process, culminating in a slow elimination with a long terminal phase. The average half-life in the final phase is 40 hours (27.7–43.6 hours). After ingestion, it is quickly absorbed from the gastrointestinal tract. Cmax in plasma is reached in 1.5–3 h. The absolute bioavailability averages 40%. Eating does not affect the degree of absorption. Binding to plasma proteins is 13.5%. Intensively binds to blood cells and especially platelets (78%). It penetrates well into tissues and lingers in them for a long time. Large quantities are determined in the spleen, liver, kidneys, lungs and thymus, moderate - in the heart and muscles, the minimum - in adipose tissue and bone marrow. Does not penetrate the BBB. The concentration in the lungs is 300 times higher than the concentration in plasma. It is metabolized in the liver, mainly under the action of the isoform of the CYP 3A4 enzyme, which belongs to the cytochrome P450 system. Forms a number of metabolites, one of them - diacetylvorelbine, which is the main in the blood, retains antitumor activity. It is excreted mainly with bile. The pharmacokinetics of Navelbine, administered at a dose of 20 mg / m2 weekly in patients with moderate and severe liver failure, do not change. Pharmacokinetics does not depend on the age of patients.
Indications
Non-small cell lung cancer, breast cancer, prostate cancer, resistant to hormone therapy (in combination with small doses of oral corticosteroids).
Contraindications
Hypersensitivity to vinca alkaloids or other components of the drug; neutrophil count less than 1500 cells / mcl blood; the content of platelets is less than 75,000 cells / mcl of blood (with a / in the introduction) and less than 100,000 cells / mcl (with ingestion); severe infection (concomitant with the prescription of the drug or transferred within 2 weeks); severe liver failure,not related to the tumor process; the need for constant oxygen therapy (in patients with a lung tumor); diseases and conditions leading to a decrease in absorption in the gastrointestinal tract (for capsules); pregnancy, breastfeeding period. Use with caution in case of respiratory failure, inhibition of bone marrow hematopoiesis (including after previous chemotherapy or radiation treatment), constipation or a history of intestinal obstruction in the anamnesis, a history of neuropathy.
Use during pregnancy and lactation
Contraindicated in pregnancy. At the time of treatment should stop breastfeeding.
Dosage and administration
Navelbin is used both as monotherapy and in combination with other anticancer drugs. When choosing a dose and mode of administration in each individual case, refer to the special literature. Capsules. Inside, entirely, without chewing and not dissolving in the mouth, drinking water. In monotherapy, the recommended dose is 60 mg / m2 once a week. After the third dose, the dose is increased to 80 mg / m2 once a week. Increasing the dose from 60 to 80 mg / m2 can be carried out if, during 3 weeks of Navelbina intake, 4th degree neutropenia (<500 cells / mcl) was not observed, or there was 1 episode of 3th degree neutropenia (<1000 - ≥500 cells / mcl) , and the neutrophil count before the next intake is not lower than 1500 cells / μl. In case if before taking the drug in a dose of 80 mg / m2, neutropenia of 4 degrees (<500 cells / μL3) or 2 cases of neutropenia of 3 degrees (<1000 - ≥500 cells / μl), then in the next 3 doses, the dose should be reduced from 80 to 60 mg / m2 per week. In case the neutrophil content is not less than 500 cells / mcl or no more than 1 neutrophil reduction in the range of 500–1000 cells / mcl during 3 weeks of Navelbin intake at a dose of 60 mg / m2 (according to the above recommendations), it was possible to increase the dose of the drug from 60 to 80 mg / m2 per week. For patients with BSA≥2 m2, the total single dose of Navelbine taken orally should not exceed 120 mg per week when prescribing the drug at a dose of 60 mg / m2 and 160 mg per week when prescribing the drug at a dose of 80 mg / m2. The use of Navelbine orally in doses of 60 and 80 mg / m2 corresponds to the intravenous injection arata in doses of 25 and 30 mg / m2. During polychemotherapy, the dose and frequency of drug administration (both in / in and inwards) depend on the specific program of antitumor therapy. mcl of blood (with a / in the introduction) or <100,000 (by ingestion) the next injection or ingestion of the drug is put off for 1 week.If, due to hematological toxicity, it was necessary to refrain from 3 weekly injections or administration of the drug, it is recommended to stop using Navelbine. : safety and efficacy of navelbine in children has not been studied. Elderly people: there are no special instructions for use.
Side effects
From the side of blood-forming organs: very often - neutropenia, anemia, thrombocytopenia, the addition of secondary infections against the background of oppression of bone marrow hematopoiesis; often - fever (> 38 ° C) on the background of neutropenia; sometimes - sepsis, septicemia; extremely rarely - complicated septicemia, in some cases leading to death. The smallest number of neutrophils is observed on days 7–10 from the start of therapy, recovery occurs in the next 5–7 days. Cumulative hematotoxicity is not observed. From the immune system: rarely - anaphylactic shock or angioedema. From the nervous system: very often - paresthesia, hyperesthesia, decrease or loss of deep tendon reflexes; often - weakness in the legs; sometimes - severe paresthesias with sensory and motor symptoms, as a rule, of a reversible nature. From the cardiovascular system: sometimes - increase or decrease in blood pressure, heat flushes and cold extremities; rarely - ischemic heart disease (angina pectoris, myocardial infarction), severe hypotension, collapse; extremely rarely - tachycardia, palpitations, heart rhythm disturbances. For the respiratory system: sometimes - shortness of breath, bronchospasm; rarely - interstitial pneumonia (with combination therapy with mitomycin), acute respiratory distress syndrome. From the digestive system: very often - nausea, vomiting, stomatitis, constipation, diarrhea, transient increase in liver function tests (ALT, AST); rarely - pancreatitis, increased bilirubin, intestinal paresis. On the skin and skin appendages: often - alopecia, rarely - skin rashes. Local disorders: often - pain / burning or redness at the injection site, discoloration of veins, phlebitis; with extravasation - cellulite,necrosis of surrounding tissues is possible. Others: often - increased fatigue, myalgia, arthralgia, fever, pains of various localization, including chest pain, pain in the lower jaw and in the area of tumor formations; rarely, hyponatremia; very rarely, hemorrhagic cystitis and inadequate secretion of antidiuretic hormone syndrome.
Overdose
The main expected manifestations of overdose include suppression of bone marrow function and manifestation of neurotoxicity. The specific antidote is unknown. Treatment: hospitalization of the patient, carrying out careful control over the functions of vital organs. Symptomatic therapy.
Interaction with other drugs
With simultaneous use of the drug with other drugs that have a toxic effect on the bone marrow (regardless of the method of administration), side effects associated with myelosuppression may be enhanced. Acute respiratory failure may develop with co-administration with mitomycin C. Application on the background of radiation therapy leads to radiosensitization. With the use of Navelbine after radiation therapy, the re-development of radiation reactions is possible. Simultaneous use of the drug with inducers and inhibitors of cytochrome P450 can lead to changes in the pharmacokinetics of vinorelbine.
special instructions
Treatment with Navelbin should be carried out under the supervision of a physician with experience with anticancer drugs. In case of severe liver dysfunction, the dose of Navelbine should be reduced by 33%. If the kidney function is impaired, the patient’s condition should be monitored. If dyspnea, cough or hypoxia of unknown etiology occurs, the patient should be examined to exclude pulmonary toxicity. In case of extravasation, the infusion of the drug should be blows immediately stop, the remaining dose is injected into another vein. If nausea or vomiting occurs after taking Navelbina capsules, the same dose should not be taken again. During and for at least three months after stopping the therapy, you should use reliable contraceptive methods .If the active substance enters the oral cavity, it is recommended to rinse the mouth with water or any saline solution. If Navelbina gets into the eyes, rinse them thoroughly and thoroughly with water.Sorbitol is part of the drug. Navelbine should not be used in patients with hereditary fructose intolerance. Control of laboratory parameters The drug treatment is carried out under strict hematological control, determining the number of leukocytes, neutrophils, platelets and hemoglobin levels before each next injection or oral administration. With a decrease in the number of neutrophils less than 1500 / μl and / or platelets less than 75,000 / μl (for intravenous administration) or less than 100,000 / μl (for ingestion), the use of the next dose of the drug is postponed until the indicators normalize, while monitoring the patient’s condition.