Navelbine, 20mg capsules, 1pc

Composition

1 capsule contains:

Active ingredients:

vinorelbine tartrate is 41.55 mg, which corresponds to a vinorelbine content of 30 mg.

Auxiliary substances:

anhydrous ethanol – 7.5 mg,

purified water-18.75 mg,

glycerol-3 mg,

macrogol 400-q. s. up to 262.5 mg.

Capsule shell composition:

gelatin, glycerol 85%, anidrisorb 85/70 (D-sorbitol,1,4-sorbitan, mannitol, higher polyols), medium-chain triglycerides PHOSAL 53 MST (phosphatidylcholine, glycerides, ethanol), red iron oxide (E 172), titanium dioxide (E 171).

The blister contains 1 capsule. The package contains 1 blister.

Pharmacological action

Pharmacodynamics

Antitumor drug from the group of vincaalkaloids (pink periwinkle alkaloid obtained by semi-synthetic means). The drug blocks cell mitosis at the G2-M metaphase stage, causing cell death during interphase or during subsequent mitosis.

At the molecular level, it affects the dynamic equilibrium of tubulin in the microtubule apparatus of the cell. Navelbin suppresses tubulin polymerization by binding mainly to mitotic microtubules, and in higher concentrations also affects axonal microtubules. The induction of tubulin spiralization under the action of Navelbin is less pronounced than with the use of vincristine.

Pharmacokinetics

Suction and distribution

After oral use, it is rapidly absorbed from the gastrointestinal tract. Cmax of vinorelbine is reached in 1.5-3 hours. Absolute bioavailability on average is 40%. Food intake does not affect the degree of absorption.

After intravenous use, the kinetics of vinorelbine is a three-phase exponential process.

Binding to plasma proteins is 13.5%. Intensely binds to blood cells and especially platelets (78%). It penetrates well into the tissues and stays in them for a long time. High concentrations of vinorelbine are detected in the spleen, liver, kidneys, lungs and thymus gland, moderate – in the heart and muscles, minimal-in adipose tissue and bone marrow. The concentration in the lungs is 300 times higher than the concentration in the plasma. It does not penetrate the BBB.

Metabolism and elimination

Biotransformed in the liver, mainly under the action of the CYP3A4 isoenzyme with the formation of a number of metabolites; the main one determined in the blood is diacetylvinorelbine, which retains antitumor activity. It is mainly excreted in the bile. The average T1 / 2 in the terminal phase is 40 hours (27.7-43.6 hours).

Pharmacokinetics in special clinical cases

, the pharmacokinetic parameters of Navelbine (administered at a dose of 20 mg/m2 weekly) do not depend on the age of patients and do not change in moderate or severe hepatic insufficiency.

Indications

• Non-small cell lung cancer;
• breast cancer;
• prostate cancer resistant to hormone therapy (in combination with small doses of corticosteroids for oral use).

Use during pregnancy and lactation

Navelbine is contraindicated for use during pregnancy and lactation (breastfeeding).

Contraindications

• The neutrophil count less than 1500/µl;
• platelet count less than 75 000/µl (for/in the introduction) and less than 100 000/µl (oral);
• serious infectious diseases during the initiation of therapy or postponed in the past two weeks;
• severe impairment of liver function, not associated with the tumor process;
• the need for continuous oxygen therapy in patients with lung tumor;
• diseases and conditions, leading to decreased absorption from the gastrointestinal tract (oral);
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to the drug and to other vinylchloride.

With caution: prescribe the drug for respiratory failure, suppression of bone marrow hematopoiesis (including after previous chemotherapy or radiation therapy), constipation or a history of intestinal obstruction, neuropathy in the anamnesis.

Side effects

The following side effects were more common than in isolated cases. The following criteria were used to assess the frequency of adverse events:

• very often (> 1/10);>
• often ( > 1/100,1/10);>
• sometimes ( > 1/1000,1/100);>
• rarely ( > 1/10 000,1/1000);>
• extremely rarely (1/10 000).

From the hematopoietic system: very often – neutropenia, anemia, thrombocytopenia, attachment of secondary infections against the background of inhibition of bone marrow hematopoiesis; often-fever (38°C) against the background of neutropenia; sometimes-sepsis, septicemia; extremely rarely-complicated septicemia, in some cases leading to death. The lowest number of neutrophils is observed on 7-10 days from the start of therapy, recovery occurs in the next 5-7 days. No accumulation of hematotoxicity was observed.

From the peripheral nervous system: very often – paresthesia, hyperesthesia, reduction or loss of deep tendon reflexes; often-weakness in the legs; sometimes-severe paresthesia with sensory and motor symptoms, usually reversible.

From the cardiovascular system: sometimes-an increase or decrease in blood pressure, hot flashes and cold extremities; rarely-IHD (angina pectoris, myocardial infarction), severe hypotension, collapse; extremely rarely-tachycardia, palpitations, cardiac arrhythmia.

From the respiratory system: sometimes – shortness of breath, 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 (ALT, ACT); rarely – pancreatitis, increased bilirubin levels, intestinal paresis.

From the immune system: rarely – anaphylactic shock, angioedema.

Dermatological reactions: often-alopecia; rarely-skin rashes.

Local reactions: often-pain/burning or redness at the injection site, discoloration of the vein, phlebitis; with extravasation-cellulite; possibly-necrosis of the surrounding tissues.

Other: often-increased fatigue, myalgia, arthralgia, fever, pain of various localization, including chest pain, pain in the lower jaw and in the area of tumor formations; rarely-hyponatremia; very rarely-hemorrhagic cystitis and syndrome of inadequate ADH secretion.

Interaction

When combined with other cytostatics, side effects may be mutually aggravated, primarily myelosuppression.

When combined with mitomycin C, acute respiratory failure may develop.

When used together with paclitaxel, the risk of neurotoxicity increases.

Use during radiation therapy leads to radiosensitization. The use of Navelbine after radiation therapy may lead to repeated occurrence of radiation reactions.

Concomitant use of the drug with inducers and inhibitors of cytochrome P450 isoenzymes may lead to changes in the pharmacokinetics of vinorelbine.

How to take, course of use and dosage

Navelbine is used both as monotherapy and in combination with other antitumor drugs. When choosing the dose and mode of use in each individual case, you should refer to the special literature.

Navelbin concentrate is administered strictly intravenously in the form of a 6-10-minute infusion.

Capsules are taken orally whole, washed down with water without chewing or dissolving them in the mouth.

In the monotherapy mode, the usual dose of the drug for intravenous use is 25-30 mg/m2 of body surface area once a week. Navelbine is diluted in 0.9% sodium chloride solution or 5% dextrose solution to a concentration of 1.0-2.0 mg / ml (on average in 50 ml). After use of the drug, the vein should be flushed, adding at least 250 ml of 0.9% sodium chloride solution or 5% dextrose solution.

For patients with a body surface area of 2 m2 or more, a single dose of Navelbin for intravenous use should not exceed 60 mg.

The recommended single starting dose of Navelbine for oral use is 60 mg/m2 of body surface area once a week. After the third dose, it is recommended to increase the dose to 80 mg / m2.

Increasing the dose of 60 mg/m 2 to 80 mg/m 2 can be carried out, unless within three weeks of taking Navelbine not marked degree 4 neutropenia (less than 500/µl), or was one episode of grade 3 neutropenia (less than 1000/µl, but more than 500/µl), and the number of neutrophils before the next reception is not below 1500/µl.

The minimum number of neutrophils (cells/µl) recorded in the first 3 weeks of oral use of Navelbine at a dose of 60 mg / m2 per week

>1000>

≥ 500 and

≥ 500 and

Recommended dose starting with the 4th dose

80 mg / m2

60 mg/m2

If there is grade 4 neutropenia (less than 500/mcl) or 2 cases of grade 3 neutropenia (less than 1000/mcl, but more than 500/mcl) when taking Navelbine at a dose of 80 mg/m2, then the dose of Navelbine should be reduced from 80 to 60 mg/m2 per week in the next 3 doses.

The minimum number of neutrophils (cells/µl) recorded in the first 3 weeks of oral use of Navelbine at a dose of 80 mg / m2 per week

>1000>

≥ 500 and

≥ 500 and

< 500

Recommended dose starting with the 4th dose

80 mg / m2

60 mg/m2

If the neutrophil count did not decrease below 500 / µl, or there was no more than one decrease in the number of neutrophils in the range from 500 to 1000/µl during the three weeks of taking Navelbine at a dose of 60 mg/m2 (according to the above recommendations), you can again increase the dose of the drug from 60 to 80 mg/m2 per week.

Recommended oral doses of Navelbine based on the patient’s body surface area (BSA) are given in the following table.

Body surface area (m2)

60 mg / m2

80 mg/m2

Dose (mg) per week

0.95 to 1.0

60

1.05 to 1.14

70

1.15 to 1.24

70

1.25 to 1.34

80

1.35 to 1.44

80

1.44 to 1.54

90

1.55 to 1.64

100

1.65 to 1.74

100

1.75 to 1.84

110

1.85 to 1.94

110

1.95 or more

120

For patients with BSA 2 m 2 or more, the total single oral dose of Navelbine should never exceed 120 mg per week when the drug is prescribed at a dose of 60 mg / m2 and 160 mg per week at a dose of 80 mg/m2.

Oral use of Navelbine at doses of 60 mg / m2 and 80 mg / m2 corresponds to intravenous use of Navelbine at doses of 25 mg/m2 and 30 mg/m2.

In polychemotherapy, the dose and frequency of use of Navelbine (both when administered intravenously and when taken orally) depend on the specific program of antitumor therapy.

With a decrease in the number of neutrophils less than 1500 / µl or platelets less than 75,000/µl (with intravenous use) or less than 100,000/µl (with oral use), the next use or oral use of Navelbin is postponed for 1 week. If due to hematological toxicity, it was necessary to refrain from 3 weekly injections or doses of the drug, the use of Navelbin is recommended to be discontinued.

In patients with severe hepatic insufficiency, Navelbine should be administered with caution, at a dose reduced by 33%.

The safety and efficacy of Navelbine in children has not been studied.

Special correction of the dosage regimen of Navelbine in the elderly is not required.

Overdose

Symptoms: suppression of bone marrow function, neurotoxic reactions.

Treatment: in case of overdose, the patient should be hospitalized; symptomatic therapy is carried out with careful monitoring of the functions of vital organs. The specific antidote is unknown.

Special instructions

Treatment with Navelbine should be carried out under the supervision of a doctor who has experience with antitumor drugs.

In patients with severe hepatic impairment, Navelbine doses should be reduced by 33%.

If renal function is impaired, the patient’s condition should be monitored.

If signs of neurotoxicity of 2 or more degrees appear, the use of Navelbin should be discontinued. If dyspnea, cough, or hypoxia of unknown etiology occur, the patient should be examined to rule out pulmonary toxicity.

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

In case of nausea or vomiting after taking Navelbine capsules, the same dose should not be taken again.

During and for at least three months after discontinuation of therapy, reliable methods of contraception should be used.

If the Active ingredient gets into the oral cavity, it is recommended to rinse your mouth with water or any saline solution.

If Navelbine gets into the eyes, they should be thoroughly and thoroughly rinsed with water.

Since the drug contains sorbitol, Navelbin 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 white blood cells, neutrophils, platelets and hemoglobin levels before each regular injection or oral use. With a decrease in the number of neutrophils less than 1500 / µl and/or platelets less than 75,000/µl (for intravenous use) or less than 100,000/µl (for oral use), the next dose of the drug is postponed until the indicators normalize, while the patient’s condition is monitored.

Form of production

Capsules.

Storage conditions

In a dark place, at a temperature of 2-8 °C

Shelf

life 2.5 years

Active ingredient

Vinorelbin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as directed by your doctor

Indications

Cancer