Navelbine 10 mg/ml 1 ml 10 pcs

Pharmacodynamic

The antineoplastic vinca alkaloid drug from group (vinca alkaloid derived semisynthetically). The drug blocks cell mitosis at metaphase G2-M, causing cell death during interphase or at the subsequent mitosis. At the molecular level affects the dynamic equilibrium of tubulin in the microtubule apparatus of the cell. Navelbine inhibits tubulin polymerization by binding predominantly with mitotic microtubules, and in higher concentrations also affects axonal microtubules. The induction of tubulin helix under Navelbina less pronounced than with vincristine.

pharmacokinetics

Absorption and distribution

After intake of rapidly absorbed from the gastrointestinal tract. Vinorelbine Cmax achieved after 1.5-3 hours. The absolute bioavailability on average was 40%. Food intake does not affect the extent of absorption.

After on / in the kinetics of vinorelbine is a three-phase exponential process.

Plasma protein binding is 13.5%. Intensively binds to blood cells and especially to platelets (78%). It penetrates the tissues and delayed them for a long time. High concentrations of vinorelbine are determined in the spleen, liver, kidneys, lungs and thymus, moderate – in the heart and muscles, the minimum – in the adipose tissue and bone marrow. The concentration in the lungs of 300 times the concentration in plasma. Do not cross the blood-brain barrier.

Metabolism and excretion

Biotransformiroetsa in the liver, principally under the action of the isoenzyme CYP3A4 to form several metabolites; mainly determined in the blood is diatsetilvinorelbin which retains antitumor activity. Excreted mainly in the bile. The average T1 / 2 of 40 hours (27,7-43,6 h) in the terminal phase.

Pharmacokinetics in special clinical situations

The pharmacokinetic parameters Navelbina (administered at a dose of 20 mg / m2 weekly) does not depend on the age of the patients and do not vary with moderate or severe liver failure.

Active substance:
Vinorelbine

Manufacturer

Pierre Fabre medicament France

Composition

1 ml of the concentrate comprises:

The active ingredients: Vinorelbine tartrate 13.85 mg, which corresponds to a content of 10 mg of vinorelbine base

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Excipients: Water d / and nitrogen (inert gas)

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In the vial 1 ml of concentrate. In the cold box of 10 vials. The carton 1 cold box.

Indications

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

Contraindications

• Number of neutrophils less than 1500 / l;
• platelet count less than 75,000 / microliter (to / v administration) and at least 100,000 / microliter (oral);
• severe infections during the start of therapy or deferred during the last two weeks;
• severe liver failure, unrelated to the neoplastic process;
• the need for continuous oxygen therapy in patients with lung tumor;
• diseases and conditions, resulting in decreased absorption from the gastrointestinal (for oral administration);
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to the drug and other vinca alkaloids.

Precautions: prescribed medication for respiratory failure, inhibition of bone marrow hematopoiesis (including after previous chemotherapy or radiation therapy), constipation or phenomena ileus history, a history of neuropathy

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Side effects

The following side effects were more common than in isolated cases. We used the following criteria for evaluating the frequency of occurrence of adverse events:

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

From the hematopoietic system: very often – neutropenia, anemia, thrombocytopenia, accession secondary infections on the background of suppression of bone marrow hematopoiesis; often – fever (38 ° C) for neutropenia; sometimes – sepsis, septicemia; extremely rare – complicated by septicemia, in some cases leading to death. The smallest number of neutrophils occurs 7-10 days after initiation of therapy, recovery occurs over the next 5-7 days. Cumulation gematotoksichnosti not mentioned.

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

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Since the cardiovascular system: sometimes – increase or decrease in blood pressure, hot flushes and cold extremities; rarely – ischemic heart disease (angina, myocardial infarction), hypotonia, collapse; rarely – tachycardia, palpitations, irregular heartbeat

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With the respiratory system: sometimes – shortness of breath, bronchospasm; rarely – interstitial pneumonia (in combination therapy with mitomycin), acute respiratory distress syndrome

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From the digestive system: very often – nausea, vomiting, stomatitis, constipation, diarrhea, transient increase in liver function tests (ALT, ACT); rarely – pancreatitis, increased bilirubin, intestinal paresis

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

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Dermatological reactions: often – alopecia; seldom – a skin rash

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Local reactions: often – pain / burning or redness at the injection site, change the color veins, phlebitis; when extravasation – Cellulite; possible – necrosis of surrounding tissue

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Other: often – fatigue, myalgia, arthralgia, fever, pain of different localization, including chest pain, pain in the lower jaw and in the field of tumor formation; rarely – hyponatremia; very rarely – hemorrhagic cystitis and the syndrome of inappropriate secretion of ADH

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How to accept, acceptance rate and dosage

Navelbin applied as a monotherapy, or in combination with other antineoplastic drugs. When choosing the dose and mode of administration in each individual case should be referred to specialized literature.

Concentrate Navelbina injected strictly on / in a 6-10 minutes infusion.

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

In monotherapy the usual dosage of the drug to / v administration of 25-30 mg / m2 body surface area once a week. Navelbine diluted in 0.9% sodium chloride solution or 5% dextrose to concentrations of 1.0-2.0 mg / ml (average 50 mL). After administration the vein should be flushed by introducing at least an additional 250 ml of 0.9% sodium chloride solution or 5% dextrose solution.

For patients with a body surface area of ​​2 m2 and a single dose Navelbina / v administration should not exceed 60 mg.

The recommended initial dose Navelbina single oral 60 mg / m2 body surface area once a week. After receiving the third dose should be increased to 80 mg / m2.

Increasing the dose to 60 mg / m2 to 80 mg / m2 can be accomplished if during the three weeks of Navelbina not marked neutropenia grade 4 (less than 500 / L), or was one neutropenia grade 3 episode (less than 1000 cells / mm but more than 500 / ml) and neutrophil count before the next reception of not less than 1500 / l.

The minimum number of neutrophils (cells / ml) recorded in the first 3 weeks of Navelbina oral dose of 60 mg / m2 weekly

> 1 000

≥ 500 and

≥ 500 and

The recommended dose starting with the 4th reception

80mg / m2

60mg / m2

If reception Navelbina at a dose of 80 mg / m2 marked grade 4 neutropenia (less than 500 / ml) or 2 cases of neutropenia grade 3 (less than 1000 / l, but more than 500 cells / mm) in the following 3 doses necessary to reduce the dose Navelbina from 80 to 60 mg / m2 per week.

The minimum number of neutrophils (cells / ml) recorded in the first 3 weeks of Navelbina oral dose of 80 mg / m2 weekly

> 1 000

≥ 500 and

≥ 500 and

< 500

The recommended dose starting with the 4th reception

80mg / m2

60mg / m2

If the number of neutrophils was not reduced below 500 / mm, or there was more than one to reduce the number of neutrophils in the range of 500 to 1000 / ml for three weeks of Navelbina at a dose of 60 mg / m2 (according to the above recommendations) may be again increase the dose from 60 to 80 mg / m2 per week.

Navelbina Recommended doses for oral administration according to the patient’s body surface area (BSA) are shown in the following table.

body surface area (m2)

60mg / m2

80mg / m2

Dose (mg) per week

From 0.95 to 1,0

60

From 1,05 to 1,14

70

From 1,15 to 1,24

70

From 1,25 to 1,34

80

From 1,35 to 1,44

80

From 1,44 to 1,54

90

From 1,55 to 1,64

100

From 1.65 to 1,74

100

From 1,75 to 1,84

110

From 1.85 to 1,94

110

1,95 and more

120

For patients with BSA 2 m2 and a total single dose Navelbina for oral administration should never exceed 120 mg per week when administering the drug in a dose of 60 mg / m2 and 160 mg per week at a dose of 80 mg / m2.

Application Navelbina inwards in doses of 60 mg / m2 and 80 mg / m 2 corresponds to I / Navelbina administration at doses of 25 mg / m2 and 30 mg / m2.

When chemotherapy dose and frequency of administration Navelbina (as with / in the introduction, and by ingestion) depend upon the particular tumor therapy program.

By reducing the number of neutrophils less than 1500 / l or platelets less than 75,000 / microliter (at / in the introduction) or less than 100,000 / ml (by ingestion) regular administration or ingestion Navelbina delaying for 1 week. If, due to hematological toxicity had to refrain from 3 weekly injections or dose, use Navelbina advised to stop.

Patients with severe hepatic insufficiency Navelbin should be used with caution at a dose reduced by 33%.

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

Ad hoc correction dosing regimen Navelbina in the elderly is not required.

Storage conditions

Concentrate for solution for infusion should be kept out of the reach of children, protected from light at a temperature of from 2 ° to 8 ° C.
After further dilution of the concentrate its physical and chemical stability is maintained in

Active substance

Vinorelbine

Interaction

When combined with other cytotoxic agents may mutual aggravation of side effects, in the first place – myelosuppression

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When combined with mitomycin C may develop acute respiratory failure.

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

The use of radiation therapy in the background leads to radiosensitization. Application Navelbina after radiotherapy may lead to reappearance radioreactions.

The simultaneous use of the drug with inducers and inhibitors of cytochrome P450 isozymes may alter the pharmacokinetics of vinorelbine.

Special conditions

Treatment Navelbin should be carried out under the supervision of a physician who has experience with anticancer drugs.

When expressed human liver Navelbina dose should be reduced by 33%.

If the kidney function is necessary to monitor the patient’s condition.

If signs of neurotoxicity of 2 or more degrees Navelbina use should be discontinued. When the shortness of breath, cough, or hypoxia of unknown etiology should examine the patient to rule out lung toxicity.

If extravasation of drug infusion should be discontinued immediately, the remaining dose administered in another vein.

In case of nausea or vomiting after taking the capsules Navelbina repeated the same dose should not be accepted.

At the time and for at least three months after cessation of therapy, you must use reliable methods of contraception.

After contact with the active substance in the mouth is recommended to rinse the mouth with water or any brine.

In case of contact with eyes Navelbina should be abundantly and thoroughly with water.

Tk. of the drug include sorbitol, Navelbin should not be used in patients with hereditary fructose intolerance.

Monitoring of laboratory parameters

Treatment with hematological carried out under strict control by determining the number of leukocytes, neutrophils, platelets and hemoglobin level once before each injection or ingestion. By reducing the number of neutrophils less than 1500 / l and / or platelets less than 75,000 / microliter (to / v administration) or at least 100,000 / L (oral) application of the next dose of medication should be deferred until normalization of simultaneously monitor the patient’s condition.

Overdose

Symptoms: bone marrow suppression, neurotoxic reactions

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Treatment: In case of overdose the patient should be hospitalized; symptomatic therapy with careful monitoring functions of vital organs. A specific antidote is not known.