Velbin conc. 10 mg/ml 5 ml of 1 pc.

pharmacodynamics

The antitumor preparation of vinca alkaloid group is a vinca alkaloid. Penalized tubulin polymerization during cell mitosis. Blocking mitosis in G2 + M phase and causes destruction of cells at the interface or in the subsequent mitosis. It acts mainly on mitotic microtubules; when used in high doses it has an effect on axonal microtubules. Spiraling effect tubulin caused by vinorelbine, is less pronounced than that of vincristine.

Pharmacokinetics

After the on / in the preparation traced three-phase kinetics.

Distribution

Binding to plasma proteins is 13.5%. Intensively binds to blood cells and especially to platelets (78%). It penetrates the tissues and delayed them for a long time. In large amounts determined in spleen, liver, kidney, lung, and thymus, moderate – heart and muscles; in minimal quantities – in the adipose tissue and bone marrow. It does not cross the blood-brain barrier. The concentration in the lungs of 300 times the concentration in plasma.

Metabolism

It is metabolized in the liver, principally under the action of the isoenzyme CYPZA4. It forms a series of metabolites, one of which, diatsetilvinorelbin retains antitumor activity.

breeding

The average T1 / 2 in the terminal phase is 40 (27,7-43,6) hours. Report mostly in bile.

Pharmacokinetics in special clinical situations

Pharmacokinetics of vinorelbine, administered in a dose of 20 mg / m2 weekly in patients with moderate to severe hepatic insufficiency does not change.

The pharmacokinetics of vinorelbine is not dependent on the age of the patient.

Active substance:
Vinorelbine

Manufacturer

S.K.Sindan Pharma, Romania

Composition

Active substances 1 mL vinorelbine ditartrate 13.85 mg corresponding to 10 mg of vinorelbine content.

Excipients: Water d / and – up to 1 ml.

Indications

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

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Contraindications

• The original number of neutrophils in the blood < 1500 / L, platelet count < 75,000 / ul;
• severe infections during the start of therapy or deferred during the last 2 weeks;
• severe hepatic impairment not related to the tumoral process;
• the need for continuous oxygen therapy – in patients with lung tumor;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to the drug;
• hypersensitivity to vinca alkaloids.

Precautions: use in patients with respiratory failure, inhibition of bone marrow hematopoiesis (including after previous chemotherapy or radiation therapy), constipation or phenomena ileus history, a history of neuropathy.

Side effects

Co side of hematopoiesis: neutropenia, anemia, thrombocytopenia; amid suppression of bone marrow hematopoiesis – connection of secondary infections, fever (> 38 ° C), sepsis, septicemia, very rarely – septicemia complicated, 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 noted.

Allergic reactions: seldom – anaphylactic shock or angioedema.

From the nervous system: paresthesia, hyperesthesia, reduction or loss of deep tendon reflexes, weakness in the legs, pain in the jaw rarely severe paresthesias with sensory and motor symptoms are usually reversible.

Cardio-vascular system: increased or decreased blood pressure, hot flushes and cold extremities, ischemic heart disease (angina, myocardial infarction), severe hypotension, collapse; rarely – tachycardia, palpitations and irregular heartbeat.

The respiratory system: dyspnea, bronchospasm, interstitial pneumonia (in combination therapy with mitomycin C), acute respiratory distress syndrome.

From the digestive system: nausea, vomiting, anorexia, stomatitis, constipation, diarrhea, pancreatitis, intestinal paresis, a transient increase in bilirubin levels and increase in liver transaminases.

Skin and skin appendages: alopecia, skin eruptions.

Local reactions: pain / burning or redness at the injection site, change the color veins, phlebitis; when extravasation – inflammation of subcutaneous fat necrosis of surrounding tissues.

Other: fatigue, myalgia, arthralgia, fever, pain of different localization, including pain in the chest and in the field of tumor formation, hyponatremia, hemorrhagic cystitis and the syndrome of inappropriate secretion of ADH.

How to accept, acceptance rate and dosage

Velbin 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.

Velbin administered strictly on / in a 6-10 minutes infusion.

In monotherapy the usual dose is 25-30 mg / m2 of body surface 1 time / week.

The drug was diluted in 0.9% sodium chloride solution or 5% dextrose solution to a concentration of 1.0-2.0 mg / 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 single dose Velbina at / in should not exceed 60 mg.

When chemotherapy dose and frequency of administration depends on the particular Velbina program antitumor therapy.

By reducing the content of neutrophils < 1500 / l or thrombocytopenia < 75,000 / microliter regular lay Velbina administering for 1 week. If due to hematological toxicity had to refrain from 3 weekly injections of the drug, the use of Velbina should stop.

In patients with severe hepatic insufficiency Velbin be used with caution at a dose not exceeding 20 mg / m2.

Storage conditions

Store at 2 to 8 ° C.

Active substance

Vinorelbine

Interaction

In a joint application with other cytostatics possible mutual aggravation of side effects, in the first place – myelosuppression.

When combined with mitomycin C may develop acute respiratory failure.

When used in conjunction with paclitaxel increased risk of neurotoxicity.

Application on the background radiation therapy leads to radiosensitization. In applying vinorelbine after radiotherapy may lead to reappearance of radiation reactions.

Simultaneous use of the drug with inducers and inhibitors of cytochrome P450 can lead to a change in the pharmacokinetics of vinorelbine.

Special conditions

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

Treatment is carried out under strict hematological control, determining the number of leukocytes, neutrophils, platelets and hemoglobin level once before each injection or ingestion. When the content of neutrophils below 1500 cells / ml and / or platelets below 75,000 cells / .mu.l administering the next dose should be postponed to restore normal levels.

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

If the kidney function must be enhanced monitoring of patients.

If signs of neurotoxicity 2 and a degree Velbina application should stop.

When dyspnea, coughing or hypoxia unknown etiology patient should be evaluated to exclude pulmonary toxicity.

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

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

There are no special instructions for use Velbin drug in elderly patients are missing.

The use of a pediatric

The safety and efficacy Velbina in children has not been studied.

Pregnancy and lactation

Do not use this during pregnancy and lactation (breastfeeding).

At the time and for at least 3 months after cessation of therapy is necessary to use reliable methods of contraception.

Overdose

Symptoms may be bone marrow suppression and neurotoxicity.

Treatment: the specific antidote is not known. In case of overdose, the patient should be hospitalized and carefully monitor the function of vital organs. Symptomatic therapy.