Navelbin

Vinca-alkaloid drug Navelbin belongs to the preparations of the cytostatic group. The medicine is effectively used by modern medicine in combating such a terrible disease as breast cancer, prostate cancer, oncological neoplasms in the tissues of the lungs. Despite its high toxicity, he managed to save more than one life. It is only necessary to remember that the drugs of this group should be prescribed only by a doctor, and the therapy itself should proceed under the watchful eye of a highly qualified specialist.

[1], [2], [3]

Indications Navelbin

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

• Non-malignant malignant neoplasms in the lung tissue ( lung cancer ).
• Non- malignant malignant tumors of mammary glands.
• Cancerous growths in the prostate gland that are susceptible to hormonal therapy (in combination with a small amount of glucocorticosteroids (GCS) taken orally).

[4]

Release form

Navelbin is produced by several medicinal derivatives. Form release - concentrate for the manufacture of a solution for intravenous administration. The color of the drug must fall into the color space: from a transparent, not having a color, to a pale yellow shade. This form is produced in two dosages:

Document Without a Name

	Capacity of 1 ml	Capacity of 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 an inert gas nitrogen N ₂.

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

The form of the release is capsules, oval, with a soft gelatin shell, inside of which there is a gel-like solution. A normal viscous preparation has a color from milky yellow to a saturated orange color.

	№20	№30
Concentration of vinorelbine tartrate, mg	27.7	41.55
Directly proportional to the amount of vinorelbine, mg	20	Thirty
Capsule Color	Brown - milk, with red stamping "№ 20"	Pale pink with red stamping "№ 30"
Size of the preparation	3	4

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

The units of Navelbin are packed in a blister and placed in a cardboard box.

[5]

Pharmacodynamics

The chemical compound in question refers to the vincaalkaloid group of drugs, i.e. Organic compounds with a complex chemical structure. The antitumor drug is the vinca alkaloid pink. Hence the pharmacodynamics of Navelbin 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. Such influence causes cells to die during the interphase period, when the cell "rests", or during its next division.

Vinorelbine at the level of molecules effect on the dynamic features of the interaction of a group of cellular microtubules and tubulin. In this case, the antitumor drug depresses the polymerization of tubulin, most of it by contacting mitotic microtubules. If the drug is administered a significant dosage, and the concentration of the active substance in the patient's body increases, then Navelbin begins to affect and axonal microtubules.

In the case of spiral tubulin, this characteristic manifests itself somewhat less than in the case of exposure to the patient's vincristine.

[6], [7], [8], [9], [10], [11], [12]

Pharmacokinetics

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

Laboratory studies have shown that a sufficiently high percentage of the drug is retained in the kidneys, thymus gland, spleen, liver and lungs. For example, in pulmonary tissue vinorelbine concentration is three hundred times higher than in blood, as it practically does not penetrate the blood-brain barrier (BBB). Much lower its content in muscle tissues and tissues of the heart. The minimum amount is deposited in the bone marrow and fatty tissues.

The antitumor drug enters the body, mainly intravenously, and after this pharmacokinetics, Navelbina begins to manifest itself in three-phase exponential procedures. The relationship between the plasma protein and vinorelbine is quite low and only shows 13.5%. But it shows a high percentage of binding to platelets. This figure is close to 78%. Navelbina is excellent, without much difficulty, passes into the cellular and intercellular space and for a long time is able to cumulate in it.

The bulk of Navelbin, under the influence of the isoenzyme CYP3A4, undergoes biotransformation in the liver, converting to metabolites. The main product of vinorelbine metabolism, which is in the plasma and retains its antitumor activity, is diacetylvinorelbine. It, mainly, is utilized by an organism and is allocated from it together with bile. The half-life of the antitumor drug varies from 27.7 hours to 43.6 hours, an average of forty hours. The pharmacokinetics of Navelbina is not affected at all by the age of the patient, nor by the hepatic insufficiency (both moderate and severe) present in his anamnesis.

[13], [14], [15], [16]

Dosing and administration

All dosages are calculated on the basis element of the constituents of Navelbin (not targeting the salts of tartrate). The method of application and dose is determined directly by the attending physician - oncologist and individually to each patient, based on the patient's age, the complex picture of the disease, his state of health.

Vinorelbine is administered only intravenously, slowly enough (six to ten minutes). The drug should be administered very carefully, in order 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 0.9% sodium chloride solution (NaCl) in an amount of 125 - 250 ml.

In the case of therapy, which is represented only by Navelbin, the drug is injected into the patient's body once a week. The dosage is calculated at 30 mg per square meter of the patient's body area. In the case of complex treatment involving cisplatin, the drug in question is administered in the same amount, and cisplatin is taken at a rate of 120 mg / m2. Primarily, this combination is used in the first and then on the 29th day of the course. Follow-up in the treatment protocol is usually given once every six weeks. At the end of the procedure, it is necessary to thoroughly wash 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 necessarily prescribed and, depending on the results of hematological characteristics, correction of the administered doses is carried out.

• If the clinical analysis showed a granulocyte count in the blood equal to 1500 / μl or more, then the drug is taken in the dosage given above (30 mg / m 2).
• If the result of the research varies from one to 1,500 microliters, the dosage of vinorelbine is taken at 15 mg / m 2.
• If the result is less than one thousand microliters, then the procedure is not carried out. She is delayed 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 a background of granulocytopenia, the patient has sepsis and / or elevated body temperature, as well as missed two doses of the drug, the subsequent dose of the drug in the case of an indication of the level of granulocytes and plasma from 1500 to microliter and more, should be 22.5 mg / sq.m. If this indicator falls within the limit of 1000 - 1500 / μL - the dosage is equivalent to 11.25 mg / m 2.

Hepatic insufficiency in the patient's anamnesis also requires its correction:

- At a total bilirubin level of 34.2 μmol per liter or less, the amount of Navelbin administered is determined by the figure of 30 mg / m 2.

- In the case of bilirubin, falling within the range from 35.9 to 51.3 μmol / l, the dose of vinorelbine is 15 mg / m 2.

- The total bilirubin index is 51.3 μmol / l and more - the amount of the prescribed preparation is 7.5 mg / m 2.

If Navelbin hits the skin or the mucous membrane of the eyes of medical personnel or the patient, it is necessary to rinse the place of contact in a large amount of water urgently and very carefully.

If there are side effects in the form of cough and breathing problems, the patient needs to conduct an additional examination to rule out toxins of lung tissue.

If the introduction of the drug is observed extravasation (ingestion of the drug outside the vein), the procedure must be immediately stopped. The remaining amount of the drug is injected into the ulnar vein of the other arm. If the patient's body responded with vomiting and severe nausea, then repeated administration of vinorelbine should be done with a lower dosage.

During the period of Navelbin therapy, and also within three months after its termination, it is recommended to apply reliable methods of contraception to avoid conception.

[20], [21]

Use Navelbin during pregnancy

In such a period, it is necessary for a woman to be especially cautious in choosing and accepting various pharmacological preparations, therefore, due to its toxicity, the use of Navelbin during pregnancy and the feeding of a newborn is strictly prohibited.

Contraindications

The considered pharmacological agent, in the light of its toxicity, has rather extensive limitations in use. And, in order not to harm the patient, it is necessary to know the contraindications to the use of Navelbin:

• An acute form of infectious pathology of a fungal, viral or bacterial nature.
• Increased sensitivity of the patient's body to vinorelbine and the remaining vinaalkaloids.
• Insufficient liver function.
• In the case of a severe form of suppression of the bone marrow. When thrombocytopenia and / or granulocytopenia are detected (the figure is below one thousand / μl).
• Pathology, which provokes a decrease in the absorption capacity of the gastrointestinal tract.
• Time of bearing a baby.
• Lactation.
• The constant need to use oxygen therapy in patients with a diagnosis is lung cancer.
• If the blood test shows the content:
  • The neutrophils are lower than the figure of 1,500 / μL.
  • The platelets are lower than the limit of 75,000 / μL (in the case of intravenous administration) and less than 100,000 / μL (in the case of oral administration).
• Penetration of metastases in bone marrow tissue.
• Renal dysfunction.
• Proceeding from the fact that the composition of the drug is sorbitol, it should not be attributed to patients whose history is burdened by heredity associated with hypersensitivity to fructose.

With great caution, you must enter the drug:

• In case of problems with breathing.

• The presence in the anamnesis of various degenerative-dystrophic changes of the peripheral nerves.
• When there are problems with the stool.
• If the patient has signs of blocking intestinal patency.

[17], [18]

Side effects Navelbin

The drug belongs to a group of toxic chemicals. Therefore, Navelbin's side effects are quite extensive.

• Granulocytopenia.
• Reduction of the natural contractile activity of tendons.
• Paresis - complete or partial paralysis of the intestine.
• Symptoms of anemia.
• Attacks of nausea.
• Pain symptomatology in the jaw area.
• Spasms of the bronchi.
• Problems with excretion of stool.
• Neuropathy of peripheral nerves.
• There may be problems with breathing.
• Alopecia - hair starts to fall out on a head and on all body.
• The appearance of weakness in the lower limbs.
• The provocation of the inflammatory process of the walls of the veins in the place of administration of the drug.
• Reduction of platelets in blood plasma, caused by hemorrhages and / or bleeding.
• Vomiting.
• Hemorrhagic cystitis.
• The secondary disease is able to join a secondary infection, which in rare cases can lead to a fatal outcome.
• Symptoms of fever occur at elevated temperature (about 38 ° C).
• Paralytic intestinal obstruction.
• Stomatitis.
• As in the smaller or larger side, the change in blood pressure.
• It is very rare to observe a violation of the heart rate, heart palpitations.
• Single cases, when the patient comes anaphylactic shock.
• Sometimes you can observe a skin rash.
• Diarrhea with concomitant symptoms.
• Infiltration at the site of the injection, it is possible to develop necrotic lesions of adjacent tissues.
• Appearance of painful manifestations of different localization.

[19]

Overdose

Any drug should be administered to the human body with great care. This postulate also applies to Navel'bin. Its overdose can lead to granulocytopenia, which significantly weakens the body, thereby increasing the risk of re-infection and development of superinfection. There may be signs of peripheral nerve damage, leading to the detection of neuropathy.

[22], [23]

Interactions with other drugs

In the treatment of cancer, the most productive are the protocols of therapy, which include two or more co-working drugs. But do not forget that the interaction of Navelbin with other drugs of its group lead to an increase in the general toxicity that affects the patient's body, make more intensive side symptoms, especially myelosuppression. Using the introduction of vinorelbine in combination with the radiation method, the effect on cancerous growths, in fact, we are suppressing the function of the bone marrow. There is a great risk of receiving radiosensitization. If Navelbin is appointed after a course of radiation therapy, 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 on the part of the respiratory system, usually lungs. 
Interactions Navelbin with other drugs that represent live viral or inactivated vaccines are unacceptable, since this combination completely inhibits the work of microorganisms, they die. In this case, the administration of the cytostatic and the vaccine should be significantly differentiated. Time of drug spacing in many respects depends on several factors: the type of injected immunosuppressant, the main clinical picture of the pathology, its severity, the general health of the patient, and others. In this regard, this period can vary from three months to a year.

The likelihood of neurotoxicity increases with tandem vinorelbine administration with paclitaxel.

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

[24], [25]

Storage conditions

This drug belongs to the drugs of the cytostatic group, so the storage conditions of Navelbin fully comply with the rules for the content of such pharmacological units.

• Packaging of the drug should be located inaccessible to infants.
• Concentrate for the preparation of infusion solution must be kept in a dark container, protected from direct sunlight.
• The temperature climate of the premises must meet the characteristics - from two to eight degrees.

Before the introduction of the patient into the body, the drug is diluted with 0.9% solution of sodium chloride. In the form of an infusion solution, vinorelbine retains its physico-chemical characteristics for another eight days. The temperature values of this should not cross the boundary at 25 ° C. While the microbiological stability of the solution is lost very quickly and requires immediate use. If vinorelbine is divorced and partially used, then its further responsible content falls on medical personnel who are endowed with the need to withstand all conditions of Navelbin storage prior to the intended re-use. Mostly, the drug in the diluted state is stored no more than a day in a dark place at a temperature of two to eight degrees. An exception is the preparation of a solution in specialized aseptic validated conditions.

[26]

Shelf life

2,5 - 3 years, depending on the form of release, - this is the expiration date of the considered cytostatic drug, which can be found on the drug package. After the drug has been diluted for admission, its shelf life is reduced to 24 hours storage.