Description
Pharmacological action
Pharmacodynamics
The antitumor drug from the vinca alkaloids group is a pink vinca alkaloid. It disrupts the polymerization of tubulin during cell mitosis. It blocks mitosis in the G2 + M phase and causes destruction of cells in the interphase or in subsequent mitosis. It acts mainly on mitotic microtubules when used in high doses and affects axonal microtubules. The effect of tubulin spiralization caused by vinorelbine is less pronounced than that of vincristine.
Pharmacokinetics
After iv administration of the drug, three-phase kinetics are observed.
Distribution of
Plasma protein binding is 13.5%. Intensively binds to blood cells and especially to platelets (78%). It penetrates well into tissues and lingers in them for a long time. In large quantities it is determined in the spleen, liver, kidneys, lungs and thymus gland, moderate – in the heart and muscles in minimal quantities – in adipose tissue and bone marrow. It does not penetrate the BBB. The concentration in the lungs is 300 times the concentration in the plasma.
Metabolism
Metabolized in the liver, mainly under the influence of the CYPZA4 isoenzyme. It forms a number of metabolites, one of which, diacetylvinorelbine, retains antitumor activity.
Excretion of
The average T1 / 2 in the final phase is 40 (27.7-43.6) hours. It is excreted mainly with bile.
Pharmacokinetics in special clinical cases
The pharmacokinetics of vinorelbine administered at a dose of 20 mg / m2 weekly in patients with moderate or severe liver failure does not change.
The pharmacokinetics of vinorelbine is independent of the age of the patients.
Indications
Non-small cell lung cancer
breast cancer
hormone therapy resistant prostate cancer (in combination with low doses of oral corticosteroids).
Contraindications
Original neutrophil countblood count <1500 / μl, platelet count <75 000 / μl severe infectious diseases during initiation of therapy or transferred over the past 2 weeks severe liver failure not associated with the tumor process need for ongoing oxygen therapy – in patients with lung tumor pregnancy lactation (breastfeeding) hypersensitivity to the components of the drug hypersensitivity to vinca alkaloids. Caution: the drug should be used for respiratory failure, inhibition of bone marrow hematopoiesis (including after previous chemotherapy or radiation treatment), constipation or history of intestinal obstruction in history, neuropathy in history. Special instructions Treatment with Velbin should be carried out under the supervision of a physician with experience in working with anticancer drugs. Treatment is carried out under strict hematological control, determining the number of leukocytes, neutrophils, platelets and the level of hemoglobin before each subsequent injection or ingestion. If the neutrophil content is below 1,500 cells / μl and / or platelets below 75,000 cells / μl, the next dose should be postponed until normal levels are restored. With severely impaired liver function, the dose of Velbin should be reduced by 33%. In case of impaired renal function, enhanced monitoring of the patient is necessary. If signs of neurotoxicity of 2 or more appear, Velbin should be discontinued. 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 stopped immediately, the remaining dose is injected into another vein. In case of contact with Velbin, they should be washed thoroughly and thoroughly with water. There are no specific instructions for using Velbin in elderly patients. Use with Pediatrics Safety and efficacy of Velbin in children have not been studied. Composition Active ingredients: 1 ml vinorelbine ditartrate 13.85 mg, which corresponds to the content of vinorelbine 10 mg. Excipients: d / i water – up to 1 ml. Dosage and administration Velbin is used both as monotherapy and in combination with other antitumor drugs. When choosing a dose and mode of administration in each individual case, you should consult the specialized literature. Velbin is administered strictly iv in the form of a 6-10 minute infusion. With monotherapy, the usual dose of the drug is 25-30 mg / m2 of the body surface 1 time / week. The drug is diluted in 0.9% sodium chloride solution or 5% dextrose solution to a concentration of 1.0-2.0 mg / ml. After administration of the drug, the vein should be washed, introducing an additional at least 250 ml of 0.9% sodium chloride solution or 5% dextrose solution. For patients with a body surface area> 2 m2, a single dose of Velbin with iv should not exceed 60 mg.
In polychemotherapy, the dose and frequency of Velbin administration depend on the specific antitumor therapy program.
With a decrease in neutrophil count <1500 / μl or thrombocytopenia <75 000 / μl, the next injection of Velbin is postponed for 1 week. If due to hematological toxicity it was necessary to refrain from 3 weekly injections of the drug, it is recommended to stop using Velbin. In patients with severe hepatic impairment, Velbin should be prescribed with caution in a dose not exceeding 20 mg / m2. Side effects Co side of the hematopoietic organs: neutropenia, anemia, thrombocytopenia with suppression of bone marrow hematopoiesis – accession of secondary infections, fever (> 38 ° C), sepsis, septicemia, very rarely – complicated septicemia, in some cases leading to death. The smallest number of neutrophils is observed on the 7-10th day from the start of therapy, recovery occurs in the next 5-7 days.
Cumulation of hematotoxicity was not observed.
Allergic reactions: rarely – anaphylactic shock or angioedema.
From the nervous system: paresthesia, hyperesthesia, a decrease or loss of deep tendon reflexes, weakness in the legs, pain in the jaw, rarely severe paresthesia with sensory and motor symptoms, usually reversible.
From the cardiovascular system: increase or decrease in blood pressure, hot flashes and cooling of the extremities, coronary heart disease (angina pectoris, myocardial infarction), severe hypotension, collapse is extremely rare – tachycardia, palpitations and heart rhythm disturbance.
From the respiratory system: shortness of breath, bronchospasm, interstitial pneumonia (with combination therapy with mitomycin C), acute respiratory distress syndrome.
From the digestive system: nausea, vomiting, anorexia, stomatitis, constipation, diarrhea, pancreatitis, intestinal paresis, a transient increase in bilirubin levels and an increase in hepatic transaminase activity.
From the skin and skin appendages: alopecia, skin rashes.
Local reactions: pain / burning or redness at the injection site, vein discoloration, phlebitis during extravasation – inflammation of the subcutaneous fat, necrosis of surrounding tissues.
Other: weakness, myalgia, arthralgia, fever, pains of various localization, including pain in the chest area and in the area of ² ¹ ² ¹tumor formations, hyponatremia, hemorrhagic cystitis and syndrome of inadequate secretion of ADH.
Overdose
Symptoms: suppression of bone marrow function and manifestation of neurotoxicity are possible.
Treatment: No specific antidote known. In case of overdose, the patient should be hospitalized and carefully monitor the functions of vital organs. Conducting symptomatic therapy.
Storage conditions
Store at 2 to 8 ° C.
Expiration
18 months.