Navelbin

Vincaalkaloid drug Navelbine belongs to the cytostatic group of drugs. The drug is quite effectively used by modern medicine in the fight against such a terrible disease as breast cancer, prostate cancer, and oncological tumors in lung tissue. Despite its high toxicity, it has already managed to save more than one life. It is worth remembering that drugs of this group should only be prescribed by a doctor, and the therapy itself should take place under the watchful eye of a highly qualified specialist.

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Indications Navelbin

The pharmacological agent under consideration has the characteristics of a fairly narrowly targeted effect, therefore the indications for the use of Navelbine are extensive, but limited in the localization of the effect:

• Non-small cell malignant neoplasms of the lung tissue ( lung cancer ).
• Non-small-sized malignant tumors of the mammary glands.
• Prostate cancers that are responsive to hormonal therapy (in combination with small amounts of oral glucocorticosteroids (GCS)).

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Release form

Navelbine is produced in several medicinal derivatives. The release form is a concentrate for the preparation of a solution for intravenous administration. The color of the drug must fall into the color space: from transparent, colorless, to a pale yellow shade. This form is produced in two dosages:

Document Without Name

	Capacity of 1 ml	Capacity: 5 ml
Concentration of vinorelbine tartrate, mg	13.85	69.25
Directly proportional to the amount of vinorelbine, mg	10	50

Additional chemical compounds include pure water for injection and inert gas nitrogen _N2.

The packaging bottles are made of transparent glass and placed in a special heat-insulated foam container, placed in a cardboard box.

Release form - capsules, oval, with a soft gelatin shell, inside which is a gel-like solution. The normal viscous drug has a color from milky yellow to rich orange.

	№20	№30
Concentration of vinorelbine tartrate, mg	27.7	41.55
Directly proportional to the amount of vinorelbine, mg	20	30
Color of capsules	Brown - milky, with red embossing "№20"	Pale pink with red embossing "No. 30"
Drug size	3	4

Additional chemical compounds include: glycerol, macrogol 400, anhydrous ethanol, distilled water. Combination in various dosages (this parameter depends on the capsule number).

Navelbine units are packed in a blister and placed in a cardboard box.

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Pharmacodynamics

The chemical compound in question belongs to the vinca alkaloid group of drugs, i.e. organic compounds with a complex chemical structure. The antitumor drug is an alkaloid of the pink periwinkle. This is where the pharmacodynamics of Navelbine is determined, which is expressed in the ability of the drug to block the indirect division of eukaryotic cells (mitosis), even during the metaphase G2-M. This effect causes cells to die during the interphase, when the cell is "resting", or during its next division.

Vinorelbine at the molecular level affects the dynamic features of the interaction of a group of cellular microtubules and tubulin. In this case, the antitumor drug inhibits the polymerization of tubulin, mostly by contacting mitotic microtubules. If the drug is administered in a significant dose, and the concentration of the active substance in the patient's body increases, then Navelbine begins to affect axonal microtubules.

In the case of tubulin spiralization, this characteristic is manifested somewhat less than in the case of the patient’s body being exposed to vincristine.

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Pharmacokinetics

Pharmacokinetics Navelbine is characterized by a fairly high rate of absorption of the drug into the gastrointestinal mucosa. The maximum concentration of the active substance (C _max ) in tissues is achieved approximately one and a half to three hours after its introduction into the patient's body. Absorbed from the gastrointestinal tract, vinorelbine shows biological availability within 40%.

Laboratory studies have shown that a fairly high percentage of the drug is retained in the kidneys, thymus, spleen, liver and lungs. For example, in lung tissue, the concentration of vinorelbine is three hundred times higher than in the blood, since it practically does not penetrate the blood-brain barrier (BBB). Its content in muscle tissue and heart tissue is much lower. A minimal amount of it is deposited in the bone marrow and fatty tissues.

The antitumor drug enters the body mainly intravenously, and after that the pharmacokinetics of Navelbine begins to manifest three-phase exponential processes. The connection of plasma protein and vinorelbine is quite low and shows only 13.5%. But it shows a high percentage of binding to platelets. This figure is approaching 78%. Navelbine passes perfectly, without any particular difficulties, into the cellular and intercellular space and is able to accumulate in it for a long time.

The main part of Navelbine, under the influence of the CYP3A4 isoenzyme, undergoes biotransformation in the liver, transforming into metabolites. The main product of vinorelbine metabolism, which is found in plasma and retains its antitumor activity, is diacetylvinorelbine. It is mainly utilized by the body and excreted from it together with bile. The half-life of the antitumor drug varies from 27.7 hours to 43.6 hours, which is an average of forty hours. The pharmacokinetics of Navelbine is absolutely not affected by the patient's age or liver failure (both moderate and severe) in his anamnesis.

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Dosing and administration

All dosages are calculated for the basic element of Navelbine components (not focusing on tartrate salts). The method of administration and dosage are determined directly by the attending physician - oncologist and individually for each patient, based on the patient's age, complex picture of the disease, his health condition.

Vinorelbine is administered intravenously only, quite slowly (six to ten minutes). The drug must be administered very carefully to avoid hyperemia and necrosis in the tissues of the adjacent area. The solution for invasion is prepared immediately before the procedure: the ampoule with the drug is opened and diluted with a 0.9% sodium chloride solution (NaCl) in an amount of 125 - 250 ml.

In the case of therapy, which is represented only by Navelbine, the drug is administered to the patient once a week. The dosage is calculated as 30 mg per square meter of the patient's body area. In the case of complex treatment, including cisplatin, the drug in question is prescribed in the same amount, and cisplatin is taken at the rate of 120 mg / m2. Initially, such a combination is used on the first and then on the 29th day of the course. Subsequent administration in the treatment protocol is usually prescribed once every six weeks. Upon completion of the procedure, it is necessary to thoroughly flush the vein into which the drug was administered. The treatment is done with 200 ml of 0.9% NaCl solution.
Before each procedure, a blood test is prescribed and, depending on the results of hematological characteristics, the administered doses are adjusted.

• If a clinical analysis shows the number of granulocytes in the blood equal to 1500/mcl or more, then the drug is taken in the dosage stated above (30 mg/m2).
• If the test results vary between one and one and a half thousand microliters, the dosage of vinorelbine is taken in the amount of 15 mg/m2.
• If the result obtained is below one thousand microliters, the procedure is not performed. It is postponed for one week, after which the analysis is repeated. If three weeks have passed and the level of granulocytes in the plasma has not increased, it is recommended to replace vinorelbine with another drug.

If during the treatment period against the background of granulocytopenia the patient has sepsis and/or elevated body temperature, and also two doses of the drug were missed, then the subsequent dose of the drug in case of granulocyte level in plasma from 1500 per microliter or more should be 22.5 mg/m2. If this indicator falls within the range of 1000 – 1500 /mkl – the dosage is equal to 11.25 mg/m2.

Liver failure in the patient's history also requires its own correction:

- If the total bilirubin level is 34.2 μmol per liter or less, the amount of Navelbine administered is determined by the figure of 30 mg/m2.

- In case of bilirubin level falling within the range from 35.9 to 51.3 µmol/l, the dose of vinorelbine is equal to 15 mg/m2.

- Total bilirubin level of 51.3 μmol/l or more – the prescribed amount of the drug is 7.5 mg/m2.

If Navelbine comes into contact with the skin or mucous membrane of the eyes of medical personnel or a patient, it is necessary to immediately and very thoroughly wash the area of contact with plenty of water.

If side symptoms such as coughing and breathing problems appear, the patient needs to undergo additional examination to rule out damage to the lung tissue by toxins.

If extravasation (drug entry outside the vein) is observed during drug administration, the procedure must be stopped immediately. The remaining amount of drug is injected into the elbow vein of the other arm. If the patient's body responds with vomiting and severe nausea, then repeated administration of vinorelbine must be carried out with a lower dosage.

During the period of therapy with Navelbine, as well as for three months after its completion, it is recommended to use reliable methods of contraception to avoid conception.

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Use Navelbin during pregnancy

During such a period, a woman needs to be especially careful when choosing and taking various pharmacological drugs, therefore, due to its toxicity, the use of Navelbine during pregnancy and breastfeeding is strictly prohibited.

Contraindications

The pharmacological agent in question, in light of its toxicity, has quite extensive limitations in use. And in order not to harm the patient, it is necessary to know the contraindications for the use of Navelbine:

• An acute form of infectious pathology of fungal, viral or bacterial origin.
• Increased sensitivity of the patient's body to vinorelbine and other vinca alkaloids.
• Insufficient liver function.
• In case of severe bone marrow suppression. When thrombocytopenia and/or granulocytopenia are determined (indicator below one thousand / µl).
• A pathology that causes a decrease in the adsorbing capacity of the gastrointestinal tract.
• Time to carry a baby.
• Breastfeeding.
• The constant need to use oxygen therapy in patients diagnosed with lung cancer.
• If the blood test shows the content of:
  • Neutrophils are lower than the figure of 1.5 thousand/mcl.
  • Platelets are lower than the limit of 75 thousand/μl (in case of intravenous administration) and less than 100 thousand/μl (in case of oral administration).
• Penetration of metastases into bone marrow tissue.
• Kidney dysfunction.
• Given that the drug contains sorbitol, it should not be prescribed to patients with a history of hereditary hypersensitivity to fructose.

The drug must be administered with great caution:

• In case of breathing problems.

• History of various degenerative-dystrophic changes in the peripheral nerves.
• If you have problems with your stool.
• If the patient shows signs of intestinal obstruction.

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Side effects Navelbin

The drug belongs to the group of toxic chemicals. Therefore, the side effects of Navelbine are quite extensive.

• Granulocytopenia.
• Decreased level of natural contractile activity of tendons.
• Paresis is a complete or partial paralysis of intestinal function.
• Signs of anemia.
• Attacks of nausea.
• Pain symptoms in the jaw area.
• Bronchial spasms.
• Problems with the removal of feces.
• Peripheral nerve neuropathy.
• Breathing problems may occur.
• Alopecia – hair begins to fall out on the head and all over the body.
• The appearance of weakness in the lower limbs.
• Provoking an inflammatory process in the walls of venous vessels at the site of drug administration.
• Decreased platelet count in blood plasma caused by hemorrhages and/or bleeding.
• Vomit.
• Hemorrhagic cystitis.
• A secondary infection may join the primary disease, which in rare cases can lead to death.
• Signs of fever, occurring with an elevated temperature (about 38°C).
• Paralytic intestinal obstruction.
• Stomatitis.
• How does blood pressure change, up or down?
• Very rarely, one can observe disturbances in heart rhythm and increased heart rate.
• There are isolated cases when a patient experiences anaphylactic shock.
• Sometimes a skin rash may be observed.
• Diarrhea with associated symptoms.
• Infiltrate at the injection site, possible development of necrotic lesions of adjacent tissues.
• The appearance of painful manifestations of various localizations.

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Overdose

Any medicine must be administered to the human body with great caution. This postulate also applies to Navelbine. Its overdose can lead to granulocytopenia, which significantly weakens the body, thereby increasing the risk of re-infection and the development of superinfection. Signs of damage to peripheral nerves may appear, leading to the detection of neuropathy.

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Interactions with other drugs

In the treatment of oncological diseases, the most productive are therapy protocols that include two or more drugs working together. But do not forget that the interaction of Navelbine with other drugs of its group leads to an increase in the general toxicity affecting the patient's body, make the side symptoms more intense, especially myelosuppression. Using the introduction of vinorelbine in combination with the radiation method of exposure to cancerous neoplasms, in fact we get the suppression of bone marrow function. There is a high risk of getting radiosensitization. If Navelbine is prescribed after a course of radiation therapy, then the patient may develop a recurrent radiation reaction.

The tandem combination of the drug in question and mitomycin C provokes an increase in the likelihood of acute symptoms from the respiratory system, most often the lungs.
Interactions of Navelbine with other drugs that are live viral or inactivated vaccines are unacceptable, since such a combination completely inhibits the work of microorganisms, they die. In this case, the time of taking the cytostatic and the vaccine should be significantly separated. The time of separation of drugs largely depends on several factors: the type of immunosuppressant administered, the main clinical picture of the pathology, its severity, the general health of the patient, etc. In this regard, this period can vary from three months to a year.

The risk of developing neurotoxicity increases with the tandem administration of vinorelbine with paclitaxel.

The combined use of Navelbine with inhibitors and inducers of cytochrome P450 isoenzymes is strictly prohibited. Such a tandem can radically "reshape" the characteristics of the pharmacological kinetics of the active substance of the cytostatic drug.

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Storage conditions

The drug in question belongs to the cytostatic group of drugs, therefore the storage conditions of Navelbine fully comply with the rules for the storage of such pharmacological units.

• The packaging of the drug should be kept out of the reach of children.
• The concentrate for the preparation of infusion solution must be kept in a dark container, protected from direct sunlight.
• The room temperature must meet the following specifications: from two to eight degrees.

Before administration to the patient, the drug is diluted with 0.9% sodium chloride solution. In the form of an infusion solution, vinorelbine retains its physical and chemical properties for another eight days. Temperature indicators should not cross the 25 ° C limit. While the microbiological stability of the solution is lost very quickly and requires immediate use. If vinorelbine is diluted and partially used, then its further responsible maintenance falls on the medical staff, who are endowed with the need to withstand all storage conditions of Navelbine until the expected reuse. Mostly, the drug in a diluted state is stored for no more than a day in a dark place at a temperature of two to eight degrees. An exception may be the preparation of the solution in specialized aseptic validated conditions.

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Shelf life

2.5 – 3 years, depending on the form of release, - this is the expiration date of the cytostatic drug in question, which can be found on the packaging of the drug. After the drug has been diluted for use, its shelf life is reduced to 24 hours of storage.