Vinelbin

General characteristics. Structure:

Active ingredient: 10 mg of a vinorelbin (in the form of ditartrate).

Excipients: water for injections.

Pharmacological properties:

Pharmacodynamics. Antineoplastic drug (alkaloid of a periwinkle pink, received in the semi-synthetic way) from group of vinkaalkaloid. Breaks polymerization of a tubulin in the phases G2 and M of a cellular cycle. Blocks a mitosis, causes destruction of cells in interphase (G2) or at the subsequent mitosis.

Affects preferential mitotic microtubules; at use in high doses exerts impact and on axonal microtubules. The effect of spiralling of a tubulin caused vinorelbiny is expressed more weakly, than at Vincristinum.

Pharmacokinetics. Later in/in administrations of drug the three-phase kinetics is traced.

Distribution. Linkng with proteins of plasma makes 79.6-91.2%. Intensively contacts blood cells and especially thrombocytes (78%). Well gets into fabrics and the long time is late in them. Large numbers are defined in a spleen, a liver, kidneys, lungs and a thymus, moderate - in heart and muscles, minimum - in fatty tissue, head and marrow. Does not get through GEB. Concentration in lungs by 300 times exceeds concentration in plasma.

Metabolism and removal. It is metabolized in a liver, mainly with the participation of CYP3A4 isoenzyme. Forms a number of metabolites; one of metabolites - диацетилвинорелбин keeps antineoplastic activity.

It is removed preferential with bile. Average T1/2 in a final phase makes 40 (27.7-43.6) h.

Pharmacokinetics in special clinical cases. The pharmacokinetics of the vinorelbin entered in a dose of 20 mg/sq.m weekly at patients with the moderated or expressed liver failure, does not change. The pharmacokinetics of a vinorelbin does not depend on age of patients.

Indications to use:

— widespread inoperable not small-celled cancer of a lung;

— a widespread breast cancer, refractory or progressing after the chemotherapy including anthracyclines;

— a prostate cancer, resistant to hormonal therapy (in a combination with small doses of peroral glucocorticoids).

Route of administration and doses:

Vinelbin is applied both in the form of monotherapy, and in a combination with other antineoplastic drugs. At the choice of a dose and mode of introduction in each individual case it is necessary to address special literature.

The drug Vinelbin is administered strictly in/in in the form of 6-10-minute infusion.

In the monotherapy mode the usual dose of drug makes 25-30 ^mg/sq.m of a body surface once a week. Drug is dissolved in 0.9% solution of sodium of chloride or 5% dextrose solution to concentration of 1.5-3.0 mg/ml. After administration of drug the vein should be washed out, having entered in addition not less than 250 ml of 0.9% of solution of sodium of chloride or 5% of solution of a dextrose.

For patients with the surface area of a body of ≥2 ^sq.m the single dose of Vinelbin entered in/in should not exceed 60 mg.

At polychemotherapy the dose and frequency of introduction of Vinelbin depend on the program of antineoplastic therapy.

Correction of the mode of a drug dosing Vinelbin at a gematotoksichnost (depending on hematologic indicators).

Number of neutrophils in day of administration of drug (a cell / мкл)	Percent from a starting dose of drug Vinelbin
1500	100%
from 1000 to 1499	50%
<1000	Do not enter. Repeat definition of number of neutrophils in 1 week. At the admission of 3 weekly administrations of drug in a row because of the maintenance of neutrophils <1000 cells / мкл drug Vinelbin do not resume treatment
Note: at patients with fever and/or sepsis against the background of a neutropenia during treatment by drug Vinelbin or at the admission of 2 weekly administrations of drug in a row because of the low maintenance of neutrophils of a dose at the subsequent introductions have to be the following:
1500	75%
from 1000 to 1499	37.5%
<1000	Do not enter. Repeat definition of number of neutrophils in 1 week. At the admission of 3 weekly administrations of drug in a row because of the maintenance of neutrophils <1000 cells / мкл drug Vinelbin do not resume treatment

Correction of the mode of a drug dosing Vinelbin at a liver failure:

Concentration of the general bilirubin (µmol/l)	Percent from a starting dose of drug Vinelbin
≤ 34.2	100%
from 35.9 to 51.3	50%
> 51.3	25%

Safety and Vinelbin's efficiency at children is not studied.

Any special application instructions of Vinelbin at patients of advanced age are absent.

Features of use:

Use at pregnancy and feeding by a breast. Drug is contraindicated at pregnancy and in the period of a lactation.

In time and within, at least, 3 months after the termination of therapy it is necessary to use reliable methods of contraception.

Use at abnormal liver functions. At patients with the expressed liver failure Vinelbin has to be appointed with care, in the dose which is not exceeding 20 mg/sq.m.

Use at renal failures. With care it is necessary to appoint drug at a renal failure.

Use for children. Safety and Vinelbin's efficiency at children is not studied.

Use for elderly patients. Any special application instructions of Vinelbin at elderly people are absent.

Special instructions. Treatment by Vinelbin should be carried out under observation of the doctor having experience with antineoplastic drugs.

Treatment by Vinelbin is carried out under strict hematologic control, defining number of leukocytes, neutrophils, thrombocytes and hemoglobin level before each next injection.

At the expressed drug dose abnormal liver function Vinelbin it is necessary to reduce depending on concentration of the general bilirubin.

At a renal failure the doubled watch of the patient is necessary.

To and during treatment (before each next injection) definition of activity of ALT, ACT, ShchF, concentration of bilirubin is necessary.

At emergence of signs of a neurotoxicity of the 2nd and more degree treatment by drug should be cancelled.

At emergence of an asthma, cough or hypoxia of the obscure etiology it is necessary to inspect the patient for an exception of pulmonary toxicity.

At an ekstravazation infusion of drug should be stopped immediately, the remained dose is entered into other vein.

At Vinelbin's hit in their eyes it is necessary to wash out plentifully and carefully water.

Side effects:

From system of a hemopoiesis: neutropenia, anemia, thrombocytopenia. The smallest number of neutrophils is observed for the 7-10th day from the beginning of therapy, recovery happens in the next 5-7 days. Kumulirovaniya and a gematotoksichnost is not marked out.

From immune system: seldom - an acute anaphylaxis or a Quincke's disease.

From a nervous system: decrease or loss of deep tendon jerks, a peripheral neuropathy (paresthesias, hyperesthesias), weakness in legs, pain in jaws, heavy paresthesias with touch and motor symptoms, as a rule, reversible character.

From cardiovascular system: increase or decrease in the ABP, inflows of heat to the person and a cold snap of extremities, an ischemic heart disease (stenocardia, a myocardial infarction), a collapse, tachycardia, a heart consciousness and disturbance of a cordial rhythm.

From respiratory system: an asthma, a bronchospasm, intersticial pneumonia (at a combination therapy with mitomitsiny), an acute respiratory distress syndrome, a fluid lungs.

From the alimentary system: nausea, vomiting, anorexia, stomatitis, lock, diarrhea, pancreatitis, intestines paresis, paralytic intestinal impassability, passing increase in level of bilirubin and increase in activity of hepatic transaminases.

From skin and hypodermic fabrics: alopecia, skin rashes.

Local reactions: pain/burning or reddening in the place of an injection, change of coloring of a vein, phlebitis; at an ekstravazation - an inflammation of a hypodermic fatty tissue, perhaps, a necrosis of surrounding fabrics.

Others: weakness, a mialgiya, an arthralgia, fever, pains of various localization, including pain in a thorax and in the field of tumoral educations, a hyponatremia, hemorrhagic cystitis and a syndrome of inadequate secretion of ADG.

Interaction with other medicines:

At combined use with other cytostatics perhaps mutual aggravation of side effects, first of all - miyelosupressiya.

At combined use with mitomitsiny development of acute respiratory insufficiency is possible.

At use together with paklitaksely the risk of a neurotoxicity increases.

Use against the background of radiation therapy leads to a radio sensitization. Vinelbin's use after radiation therapy can lead to repeated emergence of beam reactions.

Simultaneous use of drug with inductors and inhibitors of P450 cytochrome can lead to change of pharmacokinetics of a vinorelbin.

At simultaneous use with inhibitors of an isoenzyme CYP3A4 increase in serious side effects is possible.

Contraindications:

— initial maintenance of neutrophils <1500 cells / мкл blood and thrombocytes <75 000 cells / мкл blood;

— serious infectious diseases during the beginning of therapy or postponed within the last 2 weeks;

— the expressed insufficiency of function of a liver not connected with tumoral process;

— the need for a constant oxygenotherapy - at patients with a lung tumor;

— pregnancy;

— lactation period;

— children's age (lack of data on efficiency and safety);

— hypersensitivity to vinkaalkaloida or other components of drug.

With care it is necessary to appoint drug at respiratory insufficiency, oppression of a marrowy hemopoiesis (including after the previous chemotherapy or beam treatment), a liver and renal failure, locks or intestinal impassability in the anamnesis, a neuropathy in the anamnesis, a concomitant use of inhibitors of an isoenzyme of CYP3A4.

Overdose:

The main expected manifestations of overdose include suppression of function of marrow and manifestation of a neurotoxicity.

Treatment: symptomatic. The specific antidote is not known. In case of overdose of the patient it is necessary to hospitalize and to carefully control functions of vitals.

Storage conditions:

Drug should be stored in the unavailable to children, protected from light place at a temperature from 2 °C to 8 °C; not to freeze. A period of validity - 2 years. After additional cultivation of drug the period of storage makes 24 h (at the room temperature).

Issue conditions:

According to the recipe

Packaging:

5 ml - bottles glass transparent, type I (USP), with a capacity of 5 ml (1) - packs cardboard.