Navelbin

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Navelbin: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Prices in pharmacies

Latin name: Navelbine

ATX code: L01CA04

Active ingredient: Vinorelbine (Vinorelbine)

Producer: Pierre Fabre Medicament Production (France); Catalent Germany Eberbach, GmbH (Germany)

Description and photo update: 09.10.2019

Prices in pharmacies: from 3500 rubles.

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Navelbin is an antineoplastic drug.

Release form and composition

concentrate for the preparation of solution for infusion: transparent, colorless or pale yellow solution (1 or 5 ml each in a colorless glass bottle sealed with a butyl or chlorobutyl rubber stopper, rolled in an aluminum cap with a plastic lid; in a foam plastic thermocontainer 10 vials, 1 thermal container in a cardboard box);
capsules: soft gelatinous; 20 mg - size No. 3, oval, pale brown, with red lettering "N20"; 30 mg - size No. 4, oblong, pink, with red lettering "N30"; the contents of the capsules are a viscous solution from pale yellow to orange-yellow [1 pc. in a blister of a film of polyvinyl chloride / polyvinylidene chloride (PVC / PVDC) and aluminum foil, in a cardboard box 1 blister].

Each pack also contains instructions for the use of Navelbin.

1 ml of concentrate contains:

active substance: vinorelbine tartrate - 13.85 mg, which corresponds to 10 mg of vinorelbine base;
additional components: water for injection, nitrogen (inert gas).

1 capsule contains:

active substance: vinorelbine tartrate - 27.7 or 41.55 mg, which is equivalent to vinorelbine base in the amount of 20 and 30 mg, respectively;
additional components: macrogol 400, anhydrous ethanol, glycerol, purified water;
capsule shell: glycerin 85%, gelatin, Anidrisorb 85/70 (D-sorbitol, 1,4-sorbitan, mannitol, higher polyols), medium chain triglycerides PHOSAL 53 MST (glycerides, phosphatidylcholine, ethanol), titanium dioxide E171, iron oxide yellow E172 (20 mg), iron oxide red E172 (30 mg); composition of ink for printing - propylene glycol, hypromellose, E120.

Pharmacological properties

Pharmacodynamics

Vinorelbine is a herbal antineoplastic agent belonging to the group of semi-synthetic vinca alkaloids and isolated from a plant of the genus Vinca (periwinkle). It disrupts the process of tubulin polymerization during cellular mitosis. By inhibiting mitotic cell division at the G ₂ -M metaphase stage, Navelbin leads to cell death during interphase or during subsequent phases of mitosis. The agent mainly affects mitotic microtubules, and when administered at high doses, it also affects axonal ones.

The induction of tubulin spiralization under the action of vinorelbine is less pronounced than against the background of the use of vincristine.

Pharmacokinetics

After oral administration, vinorelbine is actively absorbed from the gastrointestinal tract (GIT). The maximum absorption period (T _max) can be from 1.5 to 3 hours, and the highest level of concentration of the active substance in the blood (C _max) is about 130 ng / ml after oral administration at a dose of 80 mg / m² of body surface. On average, the absolute bioavailability is 40%; taking Navelbine with food does not affect the degree of its absorption.

The drug has a high volume of distribution - about 21.2 l / kg (in the range of 7.5–39.7 l / kg), which confirms its extensive distribution in body tissues. The connection of the drug with blood plasma proteins is insignificant - 13.5%, however, it binds in a large volume to blood cells, mainly platelets (approximately 78%). It has been established that vinorelbine is absorbed in significant amounts by the lung tissue, where its C _max can be 300 times higher than that in blood plasma. The active substance is not found in the tissues of the brain.

The process of biotransformation is carried out in the liver, the enzyme CYP3A4 of the cytochrome P450 system is responsible for its course. All metabolites of vinorelbine are identified and inactive, with the exception of 4-O-deacetyl-vinorelbine, the main active metabolite in blood plasma; sulfo- and glucurone conjugates have not been detected.

In the final phase of elimination of vinorelbine, its average half-life is approximately 40 hours (27.7–43.6 hours). The systemic clearance of the active substance is quite high and close to the blood flow rate in the liver, approximately 0.72 l / h / kg (in the range of 0.32-1.26 l / h / kg). Most of vinorelbine is excreted in the bile in unchanged form and in the form of metabolites. Less than 20% of the administered intravenous (IV) dose is excreted through the kidneys, mainly in the form of the starting substance.

Indications for use

advanced breast cancer;
non-small cell lung cancer;
hormone-resistant prostate cancer, in combination with oral glucocorticosteroids (GCS) in low doses - additionally for the concentrate.

Contraindications

Absolute contraindications for both forms of Navelbine:

the initial platelet count is less than 100,000 cells / μl of blood;
initial absolute neutrophil count (ANC) less than 1500 cells / μl of blood;
infectious diseases present on the day of the start of the course of therapy or transferred over the past 2 weeks;
age up to 18 years;
pregnancy and lactation;
concurrent use with yellow fever vaccine;
hypersensitivity to any of the constituents of the drug.

Additional absolute contraindications for Navelbin capsules:

a history of significant resection of the stomach or duodenum;
the need for constant oxygen therapy - in patients with a lung tumor;
diseases and conditions that cause a decrease in absorption in the gastrointestinal tract;
severe hepatic dysfunction, not associated with the tumor process.

Relative contraindications (Navelbin should be used with extreme caution):

history of ischemic heart disease (CHD);
liver failure of moderate and severe (for concentrate) severity;
simultaneous use with strong inhibitors / inducers of the CYP3A4 isoenzyme;
severe general condition (for capsules).

Navelbin, instructions for use: method and dosage

Concentrate for solution for infusion

The solution for infusion, prepared from Navelbin concentrate, must be administered strictly intravenously. Intrathecal administration of the drug is strictly prohibited, since it can cause death.

The dosage regimen, dose of Navelbine, the frequency of its use and the duration of the course of treatment are set by the attending physician.

Pre-concentrate must be diluted in 20-50 ml of sodium chloride solution for injection 0.9%, or dextrose solution for injection 5%. The prepared solution is administered as a 6-10 minute infusion. Immediately after the infusion of the drug, in order to flush the vein from its residues, it is required to introduce a 0.9% sodium chloride solution in a dose of at least 250 ml.

Recommended dosage regimen of Navelbine:

advanced breast cancer, non-small cell lung cancer: the standard dose is 25-30 mg / m², as a monotherapy drug is administered 1 time per week, in combination chemotherapy - every 3 weeks on days 1 and 5 or on days 1 and 8, in dependence on the treatment protocol;
hormone-resistant prostate cancer: the standard dose is 30 mg / m² every 3 weeks on days 1 and 8 when combined with the daily use of oral corticosteroids in low doses (eg, hydrocortisone 40 mg daily).

In the case of a decrease in ANC less than 1500 cells / μL of blood and / or thrombocytopenia of less than 100,000 cells / μL of blood, the next scheduled infusion of Navelbin is postponed until the initial amount of these hematological parameters is restored.

Preparation for the administration of the solution and the administration itself should be performed by medical personnel trained in working with anticancer drugs. Healthcare professionals are required to wear eye protection, disposable face masks, gloves and an apron.

The solution for infusion should be used exclusively intravenously, therefore it is extremely important to make sure that the catheter or needle is accurately in the vein before starting its administration. In case of extravasation, it is required to immediately stop the administration of Navelbine, flush the vein with a 0.9% sodium chloride solution, and pour the rest of the dose into another vein. To reduce the risk of phlebitis in case of extravasation, IV corticosteroids should be urgently applied.

From a microbiological point of view, the prepared solution must be injected immediately. If the drug was not used immediately, the medical professional is fully responsible for the conditions and duration of its storage before infusion. At a temperature of 2 to 8 ° C in a place protected from light, the duration of such storage should not exceed 24 hours.

Capsules

Navelbin capsules are taken orally, preferably with food, swallowing whole, without dissolving or chewing in the mouth, drinking water.

The duration of the course of therapy and the frequency of Navelbin's receptions are set by the attending physician.

Recommended total single doses of the drug (in mg), taking into account the body surface area (BSA) [BSA (m2) - when Navelbine is administered at a dose of 60 or 80 (mg / m2)]:

from 0.95 to 1 - 60/80;
from 1.05 to 1.14 - 70/90;
from 1.15 to 1.24 - 70/100;
from 1.25 to 1.34 - 80/100;
from 1.35 to 1.44 - 80/110;
from 1.45 to 1.54 - 90/120;
from 1.55 to 1.64 - 100/130;
from 1.65 to 1.74 - 100/140;
from 1.75 to 1.84 - 110/140;
from 1.85 to 1.94 - 110/150;
more than 1.95 - 120/160.

For patients with BSA of 2 m² and more, the total single dose of the drug should not exceed 120 mg per week with the recommended use of the drug at a dose of 60 mg / m² and 160 mg per week at a dose of 80 mg / m².

When Navelbine is administered in monotherapy, the initial single dose is 60 mg / m² once a week. Starting from the fourth dose, it is recommended to increase the dose to 80 mg / m². This increase is allowed only if, during 3 weeks of treatment at a dose of 60 mg / m2 once a week, no decrease in ANC to a value of less than 500 cells / μl was recorded, or no more than one decrease was recorded to a value 500-1000 cells / μl.

The recommended dose of Navelbine for the start of the next dose, depending on the ANC, during the first three cycles of administration at a dose of 60 mg / m² per week:

ANC> 1000, or ≥500 and <1000 (1 episode) - 80 mg / m²;
ANC ≥500 and <1000 (2 episodes), or <500 - 60 mg / m².

If, during the use of the drug at a dose of 80 mg / m², ANC becomes less than 500 cells / μL or more than 1 time decreases to the level of 500-1000 cells / μL, it is necessary to postpone the next dose of Navelbine until the ANC is restored and use capsules at a dose of 60 mg / m² per week for 3 consecutive weeks.

In order to increase the dose again from 60 to 80 mg / m², an assessment of hematological parameters should be performed. The recommended dose of Navelbine for starting the next dose, taking into account the ANC after taking at a dose of 80 mg / m² per week:

ANC> 1000, or> 500 and <1000 (1 episode) - 80 mg / m²;
ANC> 500 and <1000 (2 episodes), or <500 - 60 mg / m².

During the use of Navelbine in a combination therapy regimen, in which oral administration of capsules and intravenous administration of a solution for infusion alternates, it should be borne in mind that oral administration in doses of 60 and 80 mg / m² provides a blood level of vinorelbine comparable to the level achieved with intravenous infusion of solution for infusion at doses of 25 and 30 mg / m², respectively.

If, due to hematological toxicity, it was necessary to abandon 3 weekly oral doses or intravenous infusion of Navelbine, its use is recommended to be discontinued.

Side effects

blood and lymphatic system: very often - anemia, leukopenia, myelosuppression, causing neutropenia (the minimum number of neutrophils is observed on the 7-10th day from the beginning of the course, recovery occurs in the next 5-7 days and there is no accumulation of hematotoxicity), thrombocytopenia; often (capsules) - grade IV neutropenia associated with an increase in body temperature above 38 ° C, febrile neutropenia (concentrate - with an unknown frequency); infrequently (capsules) - sepsis, septicemia;
parasitic and infectious diseases: very often - bacterial, fungal and viral infections of various localizations without neutropenia; often - fungal, viral and bacterial infections associated with myelosuppression and / or immunosuppression (neutropenic infections), as a rule, reversible with appropriate therapy; with an unknown frequency - neutropenic sepsis;
nervous system: very often - neurological disorders, including a decrease or loss of tendon reflexes; often (capsules) - gustatory disorder, dizziness, headache, insomnia, neuromotor disorders; infrequently (concentrate) - severe paresthesias with motor and sensory symptoms, usually reversible; ataxia (capsules); with an unknown frequency (concentrate) - weakness of the lower extremities against the background of prolonged chemotherapy;
metabolism and nutritional disorders: rarely - severe hyponatremia;
organ of vision (capsules): often - visual impairment;
Gastrointestinal tract: very often - nausea, stomatitis, constipation, vomiting, additionally for capsules - diarrhea, abdominal pain, anorexia (with an unknown frequency for the concentrate); often (capsules) - esophagitis, dysphagia: concentrate - moderate / moderate diarrhea; rarely - pancreatitis, paralytic intestinal obstruction (it is necessary to stop the administration of Navelbin until normal bowel function is restored); with an unknown frequency (capsules) - gastrointestinal bleeding;
liver and biliary tract: very often (concentrate) - a short-term increase in the activity of hepatic transaminases in the absence of clinical symptoms; often (capsules) - impaired liver function;
heart: infrequently (capsules) - heart rhythm disturbances, heart failure; rarely (concentrate) - ischemic heart disease, including angina pectoris, myocardial infarction; extremely rare (concentrate) - palpitations, heart rhythm disturbances, tachycardia, fibrillation;
vessels: often - arterial hypertension / hypotension; infrequently (concentrate) - cold extremities, hot flashes; rarely (concentrate) - severe arterial hypotension, collapse;
respiratory system, chest and mediastinal organs: infrequently - shortness of breath, cough, bronchospasm; rarely (concentrate) - interstitial pneumonia;
immune system (concentrate): with an unknown frequency - systemic allergic reactions (anaphylactic shock, anaphylactoid-type reactions, anaphylaxis);
endocrine system (concentrate): with unknown frequency - syndrome of inappropriate antidiuretic hormone secretion;
skin and subcutaneous tissue: very often - alopecia, usually of a moderate degree; often - skin reactions; rarely (concentrate) - generalized skin reactions; with an unknown frequency (concentrate) - erythema on the palms and feet;
musculoskeletal system and connective tissue: often - pain in the temporomandibular joint, myalgia, arthralgia;
kidneys and urinary tract (capsules): often - dysuria and other genitourinary disorders;
instrumental and laboratory data: very often - weight loss; often - weight gain;
general disorders and disorders at the injection site: very often - feeling unwell, weakness, fever; reactions at the injection site, including discoloration of the veins, burning pain, erythema and phlebitis at the injection site; often - chills, pain, including in the area of the tumor and in the chest, asthenia; rarely - tissue necrosis at the injection site.

Overdose

In case of an overdose of Navelbine, the main symptom is suppression of bone marrow function, in some cases in combination with fever, infection, dynamic intestinal obstruction and liver dysfunction.

There is no specific antidote. If an overdose is suspected, the patient must be hospitalized and the functions of vital organs must be carefully monitored. It is required to conduct a blood transfusion, antibiotic therapy, enter growth factors, and control of liver activity is also shown.

special instructions

The use of Navelbin is required under the supervision of a qualified doctor with experience in working with cytostatic drugs. During the course of therapy, it is necessary to carefully monitor hematological parameters - before each next administration of Navelbin, determine the hemoglobin level and the number of neutrophils, leukocytes and platelets.

If on the first day of the start of treatment there are suspicions of a concomitant infection, the patient should be examined and an assessment of the benefit-risk ratio when deciding whether to administer Navelbine should be made.

In case of development of cough, shortness of breath or hypoxia of an unexplained nature, it is recommended to examine the patient in order to exclude pulmonary toxicity.

Taking the capsules increases the risk of nausea / vomiting. The use of antiemetics is recommended as primary prevention. If vomiting occurs within the first few hours after taking Navelbine, a second dose should not be used.

In case of contact with the skin, mucous membranes or eyes, the liquid contents of the capsules in case of mechanical damage, or the concentrate, may cause burns. If the drug nevertheless gets on the above areas, they should be immediately washed with a solution of sodium chloride 0.9% or water. If the capsule is chewed or sucked by mistake, the oral cavity should also be urgently rinsed with sodium chloride solution or water.

Navelbine should not be used concurrently with X-ray therapy, especially those involving the liver.

It is not recommended to combine the use of the drug with the introduction of itraconazole, phenytoin, live attenuated vaccines.

The capsules should not be taken by patients with fructose intolerance, since sorbitol is included in their shell.

Influence on the ability to drive vehicles and complex mechanisms

Until now, the effect of Navelbin on the rate of reactions when driving vehicles or operating other mechanisms has not been studied. However, patients who have recorded the development of undesirable effects that can affect the performance of such activities (visual impairment, dizziness, and others) should not drive vehicles and other complex potentially dangerous equipment.

Application during pregnancy and lactation

During pregnancy, due to the embryotoxic effect exerted by Navelbin, its use is contraindicated.

During lactation, treatment with an anticancer drug is contraindicated. Breastfeeding should be discontinued before using the product.

Pediatric use

Navelbin therapy for patients under 18 years of age is contraindicated due to the lack of data indicating the safety and effectiveness of its use in children and adolescents.

With impaired renal function

In the presence of impaired renal function, the pharmacokinetic parameters of vinorelbine have not been studied. At the same time, given the low level of renal excretion, it is not necessary to reduce the dose of Navelbine in patients with reduced renal function.

For violations of liver function

In the presence of liver failure, the pharmacokinetics of the drug does not change. However, as a precautionary measure when using Navelbine in the form of a concentrate in patients with moderate or severe hepatic impairment, the dose should be reduced to 20 mg / m² and the hematological parameters should be carefully monitored.

Navelbine in the form of capsules with severe liver failure, not associated with the tumor process, is contraindicated to take.

Use in the elderly

The pharmacokinetics of vinorelbine in the elderly (over 70 years) does not change, but since patients of this age group may be weakened, care must be taken when increasing the dose of Navelbine.

Drug interactions

inducers and inhibitors of cytochrome P450: there may be a change in the pharmacokinetic parameters of vinorelbine;
live attenuated vaccines: it is not recommended to immunize with live (weakened) vaccines during the period of chemotherapy due to the immunosuppressive effect of Navelbine and the possible occurrence of severe infections;
cytostatics: there may be a mutual strengthening of unwanted reactions, primarily myelosuppression;
itraconazole, ketoconazole and other inhibitors of the CYP 3A4 isoenzyme: the neurotoxicity of vinorelbine increases due to an increase in its plasma level due to a decrease in liver metabolism; use these funds in combination with vinorelbine with caution;
tacrolimus, cyclosporine: the threat of severe immunosuppression increases with the risk of lymphoproliferation;
cisplatin: no mutual influence is recorded with this combination, however, the incidence of granulocytopenia with the combined use of vinorelbine and cisplatin is higher than with monotherapy with vinorelbine;
phenytoin: there may be a weakening of the anticonvulsant effect of this substance, as well as a decrease in the effectiveness and increase in the toxicity of vinorelbine;
mitomycin C: the pulmonological toxicity of this drug increases (the threat of bronchospasm and acute respiratory failure, in rare cases - interstitial pneumonia);
inducers of the CYP 3A4 isoenzyme (including rifampicin): the effectiveness decreases and the toxicity of vinorelbine increases as a result of its increased metabolism in the liver; caution should be exercised;
inducers and inhibitors of P-glycoprotein: vinca alkaloids are a substrate for P-glycoprotein, therefore, care must be taken when using vinorelbine and drugs that alter the function of this transport protein;
oral anticoagulants: the risk of mutual aggravation of undesirable effects increases, it is recommended to conduct systematic monitoring of the indicator of the international normalized ratio (INR), as well as control the general condition of the patient;
antiemetics - 5HT ₃ antagonists (granisetron, ondansetron): their effect on the pharmacokinetics of Navelbine is not recorded;
alkaline solutions: it is contraindicated to use for diluting the concentrate due to possible precipitation;
other drugs for intravenous administration: the prepared solution for infusion should not be mixed with these drugs.

Analogs

The analogues of Navelbin are Velbin, Vinkatera, Vinorelbin Kelun-Kazfarm, Maverex, Vinelbin, Vinorelbin, Vinorelbin medak, Vinorelbin-Teva, Tsituvin.

Terms and conditions of storage

Store in a place protected from light, out of reach of children, at a temperature of 2-8 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Navelbine

The few reviews of specialists and patients about Navelbina that are found on specialized sites are mostly positive. Doctors classify the drug as a vital drug that has a significant destructive effect on cancer cells. Patients also note the positive effect of Navelbin in the treatment of breast, lung and prostate cancer.

The disadvantages of the drug include serious adverse reactions, especially at the beginning of the course. Many patients express dissatisfaction that a blood test is required after each injection of the solution; they also note the high cost of Navelbin.

Price for Navelbin in pharmacies

The price for Navelbin can be:

capsules (per 1 pc.): 20 mg - 4500–4600 rubles, 30 mg - 5800–6200 rubles;
concentrate for preparation of solution for infusion 10 mg / ml, (for 10 vials of 1 ml) - 25,000-25,700 rubles.

Navelbin: prices in online pharmacies

Drug name

Price

Pharmacy

Navelbin 20 mg capsule 1 pc.

3500 RUB

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Navelbin 30 mg capsule 1 pc.

7400 RUB

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Navelbin 10 mg / ml concentrate for the preparation of solution for infusion 1 ml 10 pcs.

RUB 24,900

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!