Vinorelbine medak - instructions for use, dose, side effects, contraindications

Vinorelbine is an antitumor agent of plant origin from the group of semisynthetic vinaalkaloids isolated from a plant of the genus Vinca (periwinkle).

Vinorelbine disrupts the polymerization of tubulin in the process of cellular mitosis. It blocks mitosis of cells in the metaphase G2 + M stage, causing cell death during interphase or subsequent mitosis. Acts mainly on mitotic microtubules; When using high doses, it also has an effect on axonal microtubules. The effect of spiral tubulin, caused by vinorelbine, is less pronounced than that of vincristine.

Pharmacokinetics:

Distribution

The volume of distribution of vinorelbine is high (diathe pion volume of the distribution is 25.4 - 40.1 l / kg), which indicates the extensive distribution of vinorelbine in the tissues.

Binding to blood plasma proteins is insignificant and is 13.5%; vinorelbine actively binds to the formed elements of the blood, especially with platelets

(78%). It penetrates well into the lung tissue, where its concentration is 300 times higher than the concentration of vinorelbine in the blood plasma. Does not penetrate the blood-brain barrier.

Metabolism

Vinorelbine is metabolized in the liver by isoenzyme CYPCytochrome P450. All metabolites are identified and pharmacologically inactive, with the exception of 4-O-deacetyl-vinorelbine, which is the main active metabolite in the blood plasma. Sulfo- and glucuronic conjugates were not detected.

Excretion

The average half-life of the drug in the final phase of elimination is usually more than 40 h (27.7 - 43.6 h). The system clearance of vinorelbine is high and approaches the blood flow in the liver, averaging 0.72 l / h / kg (0.32-1.26 l / h / kg).

Vinorelbine is excreted mainly with bile in unchanged form and in the form of metabolites. Kidneys show less than 20% of the injected intravenously dose, predominantly unchangedin the form.

Pharmacokinetics in specific patient groups

Patients with impaired hepatic function

The pharmacokinetics of vinorelbine does not change in patients with insufficient liver function.

However, as a precautionary measure it is recommended to reduce the dose to 20 mg / m2 of the body surface and carefully monitor hematological parameters in patients with moderate or severe liver function impairment.

Patients with impaired renal function

The effect of renal dysfunction on the pharmacokinetic properties of vinorelbine has not been investigated. However, due to the low level of renal elimination, a decrease in vinorelbine dose in patients with impaired renal function is not required.

Elderly patients

The pharmacokinetics of vinorelbine in elderly patients does not change. However, due to the weakening of elderly patients, care should be taken when increasing the dose of vinorelbine.

Indications:

- non-small cell lung cancer, stage III and IV;

- mammary cancer.

Contraindications:

increased sensitivity to vinorelbine or other vinca alkaloids, as well as to other components of the drug;
initial number of neutrophils <1,500 cells / μl of blood;
platelet count <100,000 cells / μl of blood;
severe infectious diseases at the time of initiation of therapy, or transferred during the 2 preceding weeks of therapy;
simultaneous application with the yellow fever vaccine;
pregnancy and the period of breastfeeding;
Children under 18 years of age (safety and efficacy of vinorelbin in children have not been studied).

Carefully:

Caution should be used drug Vinorelbin medak in patients with coronary heart disease in history, a violation of liver function of moderate and severe degree, while using with inhibitors or inducers of the isoenzyme CYP ZA4.

Pregnancy and lactation:

Vinorelbine is contraindicated during pregnancy due to embryotoxic effects. Vinorelbine contraindicated during breastfeeding. Breastfeeding should be discontinued before taking the drug.

Dosing and Administration:

Vinorelbine medak is used both in the form of monotherapy, and in combination with other antitumor drugs. When choosing a dose and mode of administration in each individual case, you should refer to the special literature.

The drug is administered strictly intravenously in the form of a 5-10 minute infusion, after diluting the drug with 0.9% sodium chloride solution or 5% dextrose solution to a concentration 1,0-2,0 mg / ml.

After the introduction of the drug, the vein should be washed, introducing an addition of at least 250 ml. 0.9% solution of sodium chloride.

For patients with a body surface area> 2 m² a single dose of the drug administered intravenously should not exceed 60 mg.

In the monotherapy regime the dose of the drug is 25-30 mg / m² body surface once a week.

With polychemotherapy the dose and frequency of vinorelbine administration depend on the specific program of antitumor therapy.

With a decrease in the neutrophil count <1500 cells / μl of blood or thrombocytopenia, <75,000 cells / μl of blood, the next injection of the drug is delayed for 1 week or until the normalization of peripheral blood. If due to hematologic toxicity had to refrain from 3 weekly injections of the drug, the use of vinorelbine is recommended to be discontinued.

Correction of the dosing regimen of the preparation in case of liver failure: in patients with severe hepatic impairment Vinorelbin medac should be administered with caution, in a dose not exceeding 20 mg / m².

Children: safety and efficacy of the drug in children have not been studied.

Aged people: any special instructions for use Vinorelbin medak y elderly people are absent.

Side effects:

From the hematopoiesis: neutropenia, anemia, thrombocytopenia. Least the number of neutrophils is observed at 7-14 days from the beginning therapy, recovery of normal indicators usually occurs in subsequent 5-7 days.Cumulation of hematotoxicity was not observed.

From the nervous system: paresthesia, hyperesthesia, decrease or loss of deep tendon reflexes, weakness in the legs, pain in the jaw area, rarely severe paresthesia with sensory and motor symptoms, usually reversible. It was reported on the occurrence after prolonged use of weakness in the legs. These symptoms are usually reversible.

From the cardiovascular system: increase or decrease in blood pressure, hot flushes and cold extremities, rarely - ischemic heart disease (angina pectoris, myocardial infarction), severe hypotension, collapse; extremely rarely - tachycardia, palpitations and heart rhythm disturbances.

On the part of the respiratory system: shortness of breath, bronchospasm, rarely - interstitial pneumonia (especially with combination therapy with mitomycin), acute respiratory distress syndrome.

On the part of the system digestion: nausea, vomiting, anorexia; paresis of the intestine, paralytic intestinal obstruction, constipation, whose frequency increases with the combination of vinorelbine with other antitumor drugs; stomatitis, diarrhea, rarely - pancreatitis; a transient increase in the level of bilirubin and an increase in the activity of "hepatic" enzymes.

From the skin and skin appendages: alopecia; skin rashes, rarely - generalized skin reactions.

From the immune system: rarely anaphylactic shock or angioedema.

Local reactions: pain / burning, redness at the injection site, change in vein color,. phlebitis; when extravasation - pain, inflammation of subcutaneous fat, is possible. necrosis of surrounding tissues.

Other: a feeling of fatigue, weakness, myalgia, arthralgia, fever, pain of different localization, including pain in the chest and in the localization of the tumor, rarely severe hypnasatremia. Very rarely - hemorrhagic cystitis and syndrome of inadequate secretion of antidiuretic hormone. It is possible to attach secondary infections against the background of oppression of bone marrow hematopoiesis, fever (> 38 ° C), sepsis, septicemia; extremely rare - complicated septicemia, in some cases leading to death.

Overdose:

The main expected overdose manifestations include manifestations of neurotoxicity, suppression of bone marrow function. In case of an overdose, the patient should be hospitalized and closely monitor the functions of vital organs. The antidote is unknown. Treatment is symptomatic.

Interaction:

When combined with other cytostatics, mutual aggravation of side effects is possible, first of all - myelosuppression.

The combination of vinorelbine with cisplatin (the most frequent combination) does not lead to change in the pharmacokinetic parameters of vinorelbine. However, in this case, in comparison with the monotherapy regimen, the risk of granulocytopenia increases.

When combined with mitomycin C, acute respiratory failure may develop.

When combined with paclitaxel, the risk of neurotoxicity increases. Application on the background of radiation therapy leads to radiosensitization. The use of vinorelbine after radiation therapy can lead to the re-emergence of radiation reactions.

Simultaneous use of the drug with inducers and inhibitors of cytochrome P450 may lead to a change in the pharmacokinetics of vinorelbine.

Special instructions:

Treatment vinorelbine should be conducted under the supervision of a doctor who has experience with antitumor drugs.

The risk of vinorelbine is associated, first of all, with its depressing effect on the hematopoiesis system.Therefore, the drug should be administered under strict hematologic control, with determination of the hemoglobin level and the number of leukocytes, neutrophils, platelets before each next injection. The main dose-limiting toxic factor is neutropenia. If the neutrophil count is less than 1500 cells / μl and / or platelets below 75,000 cells / μl, the administration of the next dose should be postponed until the normal level is restored.

Patients with coronary heart disease in a history should be under careful medical supervision.

If there is a pronounced dysfunction of the liver, doses of Vinorelbine medac should be reduced by 33%; careful monitoring of the patient is recommended.

If the kidney function is impaired, intensive monitoring of the patient is necessary; correction, dose is not required, since excretion in the urine is minimal.

Patients with a history of neuropathy, regardless of etiology, should be monitored because of the possible recurrence or aggravation of these phenomena. If there are signs of neurotoxicity of the 2nd and more degree, vinorelbine should be discontinued.

When there is shortness of breath, coughing or hypoxia of unexplained etiology, the patient should be examined to exclude pulmonary toxicity.

Patients with symptoms of infection should be immediately examined and carefully observed until these symptoms disappear.

Vinorelbine medac should not be given concomitantly with radiotherapy if the area of irradiation captures the liver.

When extravasation, the infusion of the drug should be stopped immediately, the remaining dose is injected into another vein.

During treatment and for at least three months after it is completed, reliable contraceptive methods should be used.

When handling vinorelbine, all the usual instructions for the use of cytotoxic drugs should be observed.

Categorically avoid getting the product into the eyes, as this can cause considerable irritation and ulceration. If the product gets into the eyes, they should be rinsed immediately and thoroughly rinsed with water.

Form release / dosage:Concentrate for the preparation of a solution for infusions of 10 mg / ml.

Packaging:

For 10 mg / 1 ml or 50 mg / 5 ml in glass bottles.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

At a temperature of 2-8 ° C in the dark place. Do not freeze!

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006189/08

Date of registration:04.08.2008 / 19.01.2016

Expiration Date:Unlimited

The owner of the registration certificate:medac GmbHmedac GmbH Germany

Manufacturer: & nbsp

Oncommed Manufakchuring AS Czech Republic

Representation: & nbspTIRUFARM, LLCTIRUFARM, LLCRussia

Information update date: & nbsp16.10.15

Illustrated instructions

Instructions

Vinorelbine medak (Vinorelbine medac)