Welbin, 10 mg/ml concentrate 5 ml

Pharmacodynamics

Antitumor drug from the group of vincaalkaloids, it is an alkaloid of Barvinac pink. It disrupts polymerization of tubulin in the process of cell mitosis. It blocks mitosis in G2+M phase and causes cell destruction in interphase or during subsequent mitosis. It acts mainly on mitotic microtubules; when used in high doses, it also affects axonal microtubules. The effect of tubulin spiralization caused by vinorelbine is weaker than that of vincristine.

Pharmacokinetics

Three-phase kinetics can be seen following IV administration of the drug.

Distribution

The binding to plasma proteins is 13.5%. Intensively binds with blood cells and especially with platelets (78%). It penetrates into the tissues well and stays there for a long time. Detected in large amounts in the spleen, liver, kidneys, lungs and thymus gland, moderate amounts in the heart and muscles; in minimal amounts in adipose tissue and bone marrow. Does not penetrate through the GEB. Concentration in lungs is 300 times higher than in plasma.

Metabolism

Metabolized in the liver, mainly under the action of CYPZA4 isoenzyme. It forms a number of metabolites, one of which, diacetylvinorelbine, retains antitumor activity.

Excretion

The average T1/2 in the terminal phase is 40 (27.7-43.6) hours. It is excreted mainly with bile.

Pharmacokinetics in special clinical cases

The pharmacokinetics of vinorelbine administered at a dose of 20 mg/m2 weekly in patients with moderate to severe hepatic impairment are not altered.

The pharmacokinetics of vinorelbine are independent of patient age.

Indications

Active ingredient

Composition

Active ingredients:

1 ml vinorelbine ditartrate 13.85 mg, corresponding to a vinorelbine content of 10 mg.

Auxiliary substances:

water d/i – up to 1 ml.

How to take, the dosage

Velbin is used both as monotherapy and in combination with other anticancer drugs. When choosing the dose and mode of administration in each individual case the special literature should be consulted.

Velbin is administered strictly by IV as a 6-10 minute infusion.

In monotherapy, the usual dose of the drug is 25-30 mg/m2 body surface area once/week.

The drug is diluted in 0.9% sodium chloride solution or 5% dextrose solution to a concentration of 1.0-2.0 mg/ml. After the drug is injected, the vein should be flushed with at least an additional 250 ml of 0.9% sodium chloride solution or 5% dextrose solution.

In patients with a body surface area of >2 m2 a single dose of Velbin by IV should not exceed 60 mg.

In polychemotherapy the dose and frequency of administration of Velbin depend on the specific program of antitumor therapy.

If neutrophils < 1500/µl or thrombocytopenia < 75,000/µl are reduced, the next administration of Velbin should be delayed for 1 week. If, due to hematologic toxicity, 3 weekly injections of Velbin have to be withheld, discontinuation of Velbin is recommended.

In patients with significant hepatic impairment, Velbin should be administered with caution in a dose not to exceed 20 mg/m2.

Interaction

When co-administered with other cytostatics there may be mutual exacerbation of side effects, primarily myelosuppression.

In co-administration with mitomycin C acute respiratory failure may occur.

In co-administration with paclitaxel the risk of neurotoxicity increases.

The use against a background of radiation therapy leads to radiosensitization. When using vinorelbine after radiation therapy may lead to the reappearance of radiation reactions.

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

Special Instructions

The treatment with Velbin should be done under the supervision of a physician experienced in the use of antitumor drugs.

The treatment is carried out under strict hematological control, determining the number of leukocytes, neutrophils, platelets and hemoglobin levels before each injection or oral intake. If the neutrophil count is below 1,500 cells/µL and/or the platelet count is below 75,000 cells/µL, the next dose should be delayed until normal levels are restored.

In severe hepatic dysfunction, doses of Valbin should be reduced by 33%.

In case of impaired renal function, increased monitoring of the patient is necessary.

In case of signs of grade 2 or higher neurotoxicity, Velbin should be discontinued.

If dyspnea, cough, or hypoxia of unknown etiology occur, the patient should be evaluated to rule out pulmonary toxicity.

If extravasation occurs, the drug infusion should be stopped immediately, and the remaining dose administered in another vein.

In case of contact of Velbin with the eyes, they should be rinsed abundantly and thoroughly with water.

There are no special instructions for the use of Velbin in elderly patients.

Pediatric use

The safety and effectiveness of Velbin in children has not been studied.

Contraindications

With caution: the drug should be used in case of respiratory insufficiency, suppression of medullary hematopoiesis (including after previous chemotherapy or radiation therapy), constipation or bowel obstruction in anamnesis, neuropathy in anamnesis.

Side effects

Co organs of hematopoiesis: neutropenia, anemia, thrombocytopenia; against suppression of medullary hematopoiesis – accession of secondary infections, fever ( > 38 ° C), sepsis, septicemia, very rarely – complicated septicemia, in some cases leading to death. The lowest number of neutrophils is observed on days 7-10 from the beginning of therapy, recovery occurs in the next 5-7 days.

Hematotoxicity has not been observed to cumulate.

Allergic reactions: rarely anaphylactic shock or angioedema.

Nervous system disorders: paresthesias, hyperesthesia, decreased or loss of deep tendon reflexes, weakness in the legs, pain in the jaw region, rarely severe paresthesias with sensory and motor symptoms, usually reversible in nature.

Cardiovascular system disorders: increase or decrease of BP, hot flashes and coldness of extremities, CHD (angina, myocardial infarction), marked hypotension, collapse; extremely rare – tachycardia, palpitations and heart rhythm disturbances.

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

Digestive system disorders: nausea, vomiting, anorexia, stomatitis, constipation, diarrhea, pancreatitis, intestinal paresis, transient increase in bilirubin levels and increased liver transaminase activity.

Skin and skin appendages: alopecia, skin rash.

Local reactions: pain/burning or redness at the injection site, discoloration of the vein, phlebitis; in extravasation – inflammation of subcutaneous fatty tissue, necrosis of surrounding tissues.

Others: weakness, myalgia, arthralgia, fever, pain of various localizations, including pain in the chest and tumor area, hyponatremia, hemorrhagic cystitis and syndrome of inadequate secretion of ADH.

Overdose

Symptoms: bone marrow suppression and neurotoxicity may occur.

Treatment: no specific antidote is known. In case of overdose the patient should be hospitalized and functions of vital organs should be carefully monitored. Carrying out symptomatic therapy.

Pregnancy use

The use is contraindicated in pregnancy and during lactation (breastfeeding).

During and for at least 3 months after discontinuation of therapy it is necessary to use reliable methods of contraception.