Winkater - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Vinorelbine (vinca alkaloid pink, obtained semi-synthetically) - an antitumor agent from the group of vinca alkaloids. It disrupts the polymerization of tubulin in the G2 and M phases of the cell cycle.It blocks mitosis, causes destruction of cells in the interphase or subsequent mitosis. Acts mainly on mitotic microtubules; when high doses are applied, it also affects axonal microtubules. The effect of spiral tubulin, caused by vinorelbine, is less pronounced than that of vincristine.

Pharmacokinetics:After intravenous administration of the preparation, three-phase kinetics can be traced. The average half-life in the final phase is 40 (27.7-43.6) hours. The connection with plasma proteins is 79.6-91.2%. Intensively binds to platelets, lymphocytes, alpha1-acid glycoprotein, albumin and lipoproteins. It penetrates well into tissues and lingers in them for a long time. Large quantities are found in the spleen, liver, kidneys, lungs and thymus, moderate in the heart and muscles, minimal in fat tissue, head and bone marrow. Concentration in the lungs is 300 times higher than the concentration in the plasma. Metabolised in the liver, mainly under the influence of the isoform of the enzyme CYP 3A4, which belongs to the cytochrome system R₄₅₀. Forms a number of metabolites; one of the metabolites, diacetylvinorelbine, retains antitumor activity. It is excreted mainly with bile.

Pharmacokinetics of vinorelbine administered at a dose of 20 mg / m² weekly, in patients with moderate or severe hepatic impairment, does not change. The pharmacokinetics of vinorelbine does not depend on the age of the patients.

Indications:- common inoperable non-small cell lung cancer;

- common breast cancer, refractory or progressing after chemotherapy, including anthracyclines;

- Prostate cancer, resistant to hormone therapy (in combination with small doses of oral glucocorticosteroids).

Contraindications:- hypersensitivity to vinaalkaloids or other constituents of the drug;

- pronounced violations of the liver, not associated with the tumor process;

- initial neutrophil count <1500 cells / μl of blood and platelets <75,000 cells / μl of blood;

- severe infectious diseases during the initiation of therapy or transferred during the last 2 weeks;

- pregnancy and lactation;

- Children's age (lack of data on safety and efficacy).

Carefully:With respiratory failure, oppression of bone marrow hematopoiesis (including after previous chemotherapy or radiation treatment), constipation or intestinal obstruction in the anamnesis, neuropathy in the anamnesis, simultaneous administration of inhibitors of the isoenzyme CYP3A4.

Dosing and Administration:Winkater is administered strictly intravenously in the form of 6-10 intravenous bolus injection or 20-30 minute infusion.

Winkater 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.

In the monotherapy regime, the usual dose of the drug is 25-30 mg / m² body surface once a week. The drug is diluted in 0.9% solution of sodium chloride or 5% solution of dextrose to a concentration of 1.5-3.0 mg / ml. After the introduction of the drug, the vein should be washed by additionally adding at least 250 ml of a 0.9% solution of sodium chloride.

For patients with a body surface area ≥ 2 m² a single dose of Winkater should not exceed 60 mg.

Correction of the dosing regimen for liver failure:

Correction of dosing regimens Winkaters depending on hematological parameters:

The number of neutrophils on the day of drug administration (cells / μl)	Percentage of starting dose of Winkater preparation
≥/=1500	100%
1499-1000	50%
<1000	The drug is not administered. Repeat the determination of the number of neutrophils after 1 week.If due to granulocytopenia and had to refrain from 3 weekly injections of the drug, the use of vinorelbine is recommended to stop

In patients with hyperthermia and / or sepsis with a background of neutropenia during treatment or when 2 weekly injections of the drug are given in a row, due to the low number of neutrophils, the doses in subsequent administrations should be as a percentage of the previous doses:

≥/=1500	75%
1499-1000	37,5%
<1000	the drug is not administered

Correction of the dosing regimen of the drug Winkater in liver failure: patients with hepatic failure Winkater should be administered with caution, with the appearance of hyperbilirubinemia in the background of treatment with Vincatera, subsequent doses should be reduced according to the following recommendations:

Concentration of total bilirubin (μmol / L)	Percentage of starting dose of vinorelbine
≤34,2	100%
35,9-51,3	50%
<51,3	25%

Children: safety and efficacy Winkaters in children have not been studied.

Aged people: There are no specific instructions for use in the elderly.

Side effects:On the part of the hematopoiesis system: neutropenia, anemia; rarely - thrombocytopenia.The smallest number of granulocytes is observed on the 7-10th day from the beginning of therapy, recovery occurs in the next 7-14 days. Cumulation of hematotoxicity was not observed.

From the side of the central nervous system and the peripheral nervous system: decrease or loss of deep tendon reflexes, paresthesia, hyperesthesia, weakness in the legs, pain in the jaw region, headache, intestinal paresis, rarely paralytic ileus.

On the part of the digestive system: nausea, vomiting, anorexia, constipation, diarrhea, dysphagia, mucositis, pancreatitis, increased bilirubin concentration and increased hepatic transaminase activity.

On the part of the respiratory system: difficulty breathing, shortness of breath, bronchospasm, interstitial pneumonia, acute respiratory distress syndrome.

From the cardiovascular system: pain in the chest, increase or decrease in blood pressure, tachycardia, hot flushes to the face; rarely - myocardial infarction, pulmonary edema.

Local reactions: pain or redness at the injection site; when extravasation - inflammation of the subcutaneous tissue, phlebitis and, possibly, necrosis of surrounding tissues.

Other: allergic reactions; weakness, myalgia, arthralgia, skin rashes, increased creatinine concentration, hyponatremia, hemorrhagic cystitis and the syndrome of inadequate secretion of antidiuretic hormone.

Overdose:The main expected overdose manifestations include suppression of bone marrow function and manifestations of neurotoxicity. The specific antidote is not known. In case of an overdose, the patient should be hospitalized and closely monitor the functions of vital organs. Treatment is symptomatic.

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

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 R₄₅₀ may lead to a change in the pharmacokinetics of vinorelbine.

Special instructions:Treatment with Winkater should be performed under the supervision of a doctor who has experience with antitumor drugs.

The treatment is performed under strict hematological control, determining the number of leukocytes, neutrophils, platelets and hemoglobin level before each injection. If dysfunction of the liver dose Vincitors should be reduced.

If there is a violation of the kidneys, it is necessary to monitor the patient more closely.

If there are signs of neurotoxicity of the 2nd or more degree, treatment with the drug should be canceled.

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

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

During and for at least three months after discontinuation of therapy, it is necessary to use reliable contraceptive methods.

If they get into the eyes, Winkaters should be washed and rinsed thoroughly with water.

Form release / dosage:Concentrate for the preparation of a solution for infusions of 10 mg / 1 ml and 50 mg / 5 ml.

Packaging:In bottles of neutral bromosilicate hydrolytic glass (class I),ukuporennyh brombutilovymi stoppers and crimped aluminum caps with a plastic cover "flip ofl".

1 bottle with instructions for use in a cardboard box.

Storage conditions:List B.

At a temperature of 2 to 4 ° C in the dark place.

Keep out of the reach of children.

After additional dilution, the shelf life is 24 hours (at room temperature).

Shelf life:3 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016076 / 01

Date of registration:23.10.2009

Expiration Date:Unlimited

The owner of the registration certificate:Laboratory Tutor SAASIFAALaboratory Tutor SAASIFAA Argentina

Manufacturer: & nbsp

Laboratorio TUTEUR S.A.C.I.F.I.A. Argentina

Representation: & nbspHEAD OF MEDICA SAHEAD OF MEDICA SASwitzerland

Information update date: & nbsp16.02.2017

Illustrated instructions

Instructions

Winkater (Vincatera)