Navelbin

Active material: Vynorelbyn
When ATH: L01CA04
CCF: Anticancer drug
ICD-10 codes (testimony): C34, C50, C61
When CSF: 22.03.01
Manufacturer: PIERRE FABRE MEDICAMENT PRODUCTION (France)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Capsules soft gelatin, Oval, size №3, light brown, с красной надписью “N20”; содержимое капсул – вязкий раствор от светло-желтого до оранжево-желтого цвета.

Excipients: Anhydrous ethanol, Purified water, glycerol, macrogol 400.

Ingredients of the capsule shell: gelatin, glycerol 85%, anidrisorʙ 85/70 (D-sorbitol and 1,4-sorbitan), medium chain triglycerides PHOSAL 53 MST (fosfatidilxolin, glycerides, ethanol), iron oxide red (E172), iron oxide yellow (E171).

1 PC. – блистеры (1) – пачки картонные.

Capsules soft gelatin, oblong, size №4, Pink colour, с красной надписью “N30”; содержимое капсул – вязкий раствор от светло-желтого до оранжево-желтого цвета.

Excipients: Anhydrous ethanol, Purified water, glycerol, macrogol 400.

Ingredients of the capsule shell: gelatin, glycerol 85%, anidrisorʙ 85/70 (D-sorbitol and 1,4-sorbitan), medium chain triglycerides PHOSAL 53 MST (fosfatidilxolin, glycerides, ethanol), iron oxide red (E172), iron oxide yellow (E171).

1 PC. – блистеры (1) – пачки картонные.

Concentrate for solution for infusion clear, colorless to pale yellow.

Excipients: water d / and, nitrogen (inert gas).

1 мл – флаконы бесцветного стекла (10) – упаковки из пенопласта (thermocontainers) (1) – пачки картонные.

Concentrate for solution for infusion clear, colorless to pale yellow.

Excipients: water d / and, nitrogen (inert gas).

5 мл – флаконы бесцветного стекла (10) – упаковки из пенопласта (thermocontainers) (1) – пачки картонные.

Pharmacological action

An antineoplastic drug from the vinca alkaloids group (alkaloid periwinkle pink, semi-synthetic). The drug blocks cell mitosis at the metaphase stage G2-M, causing cell death during interphase or subsequent mitosis. At the molecular level, it affects the dynamic equilibrium of tubulin in the apparatus of cell microtubules. Navelbin inhibits tubulin polymerization, binding predominantly to mitotic microtubules, and at higher concentrations also affects axonal microtubules. Induction of tubulin spiralization under the action of Navelbin is less pronounced, than with vincristine.

Pharmacokinetics

Absorption and distribution

After ingestion is rapidly absorbed from the gastrointestinal tract. FROM_max vinorelbine is achieved through 1.5-3 no. The average absolute bioavailability is 40%. Eating does not affect the degree of suction.

After i.v. administration, the kinetics of vinorelbine is a three-phase exponential process.

Plasma protein binding is 13.5%. Intensively binds to blood cells and especially platelets (78%). It penetrates well into tissues and remains in them for a long time. High concentrations of vinorelbine are detected in the spleen, liver, kidney, lungs and thymus, умеренные – в сердце и мышцах, минимальные – в жировой ткани и костном мозге. Concentration in the lungs 300 times the plasma concentration. Do not cross the BBB.

Metabolism and excretion

Biotransformed in the liver, mainly under the action of the isoenzyme CYP3A4 with the formation of a number of metabolites; primary, determined in the blood is diacetylvinorelbine, which retains anti-tumor activity. It is excreted mainly with bile. Average T_1/2 in the terminal phase is 40 no (27.7-43.6 no).

Pharmacokinetics in special clinical situations

Pharmacokinetic parameters of Navelbin (administered in a dose 20 mg / m² weekly) do not depend on the age of the patients and do not change with moderate or severe hepatic impairment.

Testimony

- Non-small cell lung cancer;

- Mammary cancer;

- Prostate cancer, hormone resistant (in combination with small doses of corticosteroids for oral administration).

Dosage regimen

Navelbin is used as monotherapy, and in combination with other anticancer drugs. When choosing a dose and mode of administration in each individual case, you should refer to the special literature..

Navelbina concentrate is injected strictly intravenously in the form 6-10 minute infusion.

The capsules are taken orally whole, drinking water without chewing or dissolving them in the mouth.

In monotherapy regimen, the usual dose of the drug for intravenous administration is 25-30 mg / m² body surfaces once a week. Navelbin is bred in 0.9% sodium chloride or 5% dextrose solution to concentration 1.0-2.0 mg / ml (on average 50 ml). After administration of the drug, the vein should be flushed, introducing additionally at least 250 ml 0.9% sodium chloride solution or 5% dextrose.

For patients with body surface area 2 m² and more single dose of Navelbine for intravenous administration should not exceed 60 mg.

The recommended single initial dose of Navelbine for oral administration is 60 mg / m² body surfaces once a week. After the third dose, it is recommended to increase the dose to 80 mg / m².

Dose increase with 60 mg / m² to 80 mg / m² can be done, if no neutropenia has been noted within three weeks of taking Navelbine 4 degrees (less than 500 / μl), or had one episode of neutropenia 3 degrees (less than 1000 / μl, but more than 500 / μl), and the number of neutrophils before the next dose is not less than 1500 / μl.

If, when taking Navelbine in a dose 80 mg / m² marked neutropenia 4 degrees (less than 500 / μl) or 2 case of neutropenia 3 degrees (less than 1000 / μl, but more than 500 / μl), subsequent 3 taking it is necessary to reduce the dose of Navelbine with 80 to 60 mg / m² in Week.

If the number of neutrophils did not fall below 500 / μL, or there was no more than one decrease in neutrophil counts ranging from 500 up to 1000 / μl within three weeks of taking Navelbine in a dose 60 mg / m² (according to the recommendations above), you can increase the dose of the drug again with 60 to 80 mg / m² in Week.

Recommended doses of Navelbine for oral administration, depending on the patient's body surface area (BSA) are given in the following table.

For BSA patients 2 m² and the more general single dose of Navelbine for oral administration should never exceed 120 mg per week when prescribing the drug in a dose 60 mg / m² and 160 mg per week at dose 80 mg / m².

Application of Navelbine inside in doses 60 mg / m² and 80 mg / m² corresponds to intravenous administration of Navelbine in doses 25 mg / m² and 30 mg / m².

At polychemotherapy dose and frequency of administration of Navelbine (as with i.v. introduction, and when taken orally) depend on the specific anticancer therapy program.

With a decrease in the number of neutrophils less than 1500 / μl or platelets less 75 000/l (at / in the introduction) or less 100 000/l (ingestion) the next administration or ingestion of Navelbina is postponed for 1 week. If due to hematological toxicity it was necessary to refrain from 3 weekly injections or doses of the drug, it is recommended to stop using Navelbine.

Patients with severe hepatic insufficiency Navelbine should be used with caution., dose, reduced by 33%.

Safety and efficacy of using Navelbin in children It has not been studied.

Special correction of the dosage regimen for Navelbina the elderly not required.

Side effect

The following side effects were more common, than in isolated cases. The following criteria were used to assess the incidence of adverse events: Often (>1/10); often (>1/100,1/10); sometimes (>1/1000, 1/100); rarely (>1/10 000, 1/1000); rarely (1/10 000).

From the hematopoietic system: очень часто – нейтропения, anemia, thrombocytopenia, accession of secondary infections against the background of inhibition of bone marrow hematopoiesis; часто – лихорадка (38° C) against the backdrop of neutropenia; иногда – сепсис, septicemia; крайне редко – осложненная септицемия, in some cases fatal. The smallest number of neutrophils is observed on 7-10 day from the start of therapy, recovery occurs in subsequent 5-7 days. No accumulation of hematotoxicity was observed.

On the part of the peripheral nervous system: очень часто – парестезии, hyperesthesia, decreased or absent deep tendon reflexes; часто – слабость в ногах; sometimes severe paresthesias with sensory and motor symptoms, usually, reversible.

Cardio-vascular system: иногда – повышение или снижение АД, hot flashes and cold extremities; редко – ИБС (angina, myocardial infarction), severe hypotension, collapse; крайне редко – тахикардия, heartbeat, irregular heartbeat.

The respiratory system: иногда – одышка, bronchospasm; rarely - interstitial pneumonia (in 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 (GOLD, ACT); редко – панкреатит, increased levels of bilirubin, enteroplegia.

On the part of the immune system: rarely - anaphylactic shock, angioedema.

Dermatological reactions: часто – алопеция; rarely skin rashes.

Local reactions: часто – боль/жжение или покраснение в месте инъекции, vein discoloration, phlebitis; при экстравазации – целлюлит; возможно – некроз окружающих тканей.

Other: часто – повышенная утомляемость, mialgii, artralgii, fever, pain of various localization, including chest pain, pain in the lower jaw and in the area of ​​tumor formations; редко – гипонатриемия; очень редко – геморрагический цистит и синдром неадекватной секреции АДГ.

Contraindications

- the number of neutrophils less than 1500 / μl;

- platelet count is less 75 000/l (for / in the) less 100 000/l (orally);

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

- severe liver failure, not associated with a tumor process;

- the need for continuous oxygen therapy in patients with lung tumor;

- diseases and conditions, leading to a decrease in absorption from the gastrointestinal tract (orally);

- Pregnancy;

- Lactation (breast-feeding);

- hypersensitivity to the drug and to other vinca alkaloids.

FROM caution prescribe a drug for respiratory failure, suppression of bone marrow hematopoiesis (incl. after the previous chemo- or radiotherapy), a history of constipation or bowel obstruction, a history of neuropathy.

Pregnancy and lactation

Navelbin is contraindicated for use during pregnancy and lactation. (breast-feeding).

Cautions

Navelbin treatment should be carried out under medical supervision, with experience in anti-cancer drugs.

In case of severe liver dysfunction, the dose of Navelbine should be reduced by 33%.

In case of impaired renal function, it is necessary to monitor the patient's condition.

When signs of neurotoxicity appear 2 and more, the use of Navelbina should be discontinued.

When shortness of breath occurs, cough or hypoxia of unexplained etiology, the patient should be examined to exclude pulmonary toxicity.

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

If nausea or vomiting occurs after taking Navelbine capsules, do not take the same dose again..

During and for, at least, three months after stopping therapy, you must use reliable methods of contraception.

If the active substance enters the oral cavity, it is recommended to rinse the mouth with water or any saline solution.

If Navelbine gets into your eyes, rinse them thoroughly and abundantly with water..

Unnecessarily. the preparation contains sorbitol, Navelbine should not be used in patients with hereditary fructose intolerance.

Monitoring of laboratory parameters

Treatment with the drug is carried out under strict hematological control., determining the number of leukocytes, neutrophil, platelets and hemoglobin levels before each regular injection or ingestion. With a decrease in the number of neutrophils less than 1500 / μl and / or platelets less 75 000/l (for / in the) or less 100 000/l (orally) the use of the next dose of the drug is postponed until the indicators normalize, simultaneously monitor the patient's condition.

Overdose

Symptoms: Suppression of the bone marrow, neurotoxic reactions.

Treatment: in case of an overdose, the patient should be hospitalized; carry out symptomatic therapy with careful monitoring of the functions of vital organs. Spetsificheskiy antidote unknown.

Drug Interactions

When used together with other cytostatics, side effects may be mutually aggravated., в первую очередь – миелосупрессии.

When combined with mitomycin C, the development of acute respiratory failure is possible.

When used in conjunction with paclitaxel, the risk of neurotoxicity increases.

Application against the background of radiation therapy leads to radiosensitization. The use of Navelbine after radiation therapy may lead to the reappearance of radiation reactions.

Simultaneous use of the drug with inducers and inhibitors of cytochrome P isoenzymes₄₅₀ can lead to a change in the pharmacokinetics of vinorelbine.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The concentrate for the preparation of solution for infusion should be kept out of the reach of children., dark place at a temperature of 2 ° to 8 ° C. The capsules should be stored out of the reach of children at a temperature of 2 ° to 8 ° C.

After additional dilution of the concentrate, its physical and chemical stability is maintained for 8 days at room temperature (20° ± 5 ° C) or in the refrigerator (at a temperature of from 2 ° to 8 ° C.).

From a microbiological point of view, the drug after dilution should be used immediately. If the drug was not administered immediately, the healthcare professional takes responsibility for the conditions and duration of its storage prior to insertion. Usually the duration of such storage should not exceed 24 hours at a temperature of from 2 ° to 8 ° C., except, when dilution is done under controlled and validated aseptic conditions.

Срок годности концентрата – 3 year. After additional dilution of the drug with saline or glucose solution, the shelf life is 24 hours at room temperature.

Shelf life of capsules - 2.5 year.