Velbin (Concentrate) Instructions for Use

Marketing Authorization Holder

Actavis Group hf. (Iceland)

Manufactured By

Actavis Italy, S.p.A. (Italy)

Or

S.C. Sindan-Pharma S.R.L. (Romania)

Contact Information

ACTAVIS GROUP AO (Iceland)

ATC Code

L01CA04 (Vinorelbine)

Active Substance

Vinorelbine (Rec.INN registered by WHO)

Dosage Forms

	Velbin	Concentrate for solution for infusion 10 mg/1 ml: vial 1 pc.
		Concentrate for solution for infusion 10 mg/1 ml: 5 ml vial 1 pc.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion clear, from colorless to pale yellow.

Excipients : water for injections – up to 1 ml.

1 ml – glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent – alkaloid

Pharmacological Action

An antineoplastic drug from the group of vinca alkaloids, it is an alkaloid of the Madagascar periwinkle. It disrupts the polymerization of tubulin during cellular mitosis. It blocks mitosis in the G2+M phase and causes cell destruction in the interphase or during subsequent mitosis. It acts primarily on mitotic microtubules; when used in high doses, it also affects axonal microtubules. The tubulin spiralization effect caused by vinorelbine is less pronounced than that of vincristine.

Pharmacokinetics

After intravenous administration of the drug, triphasic kinetics are observed.

Distribution

Plasma protein binding is 13.5%. It intensively binds to blood cells and especially to platelets (78%). It penetrates well into tissues and is retained in them for a long time. It is found in large quantities in the spleen, liver, kidneys, lungs, and thymus; moderate amounts in the heart and muscles; minimal amounts in adipose tissue and bone marrow. It does not penetrate the blood-brain barrier. The concentration in the lungs is 300 times higher than the concentration in plasma.

Metabolism

It is metabolized in the liver, mainly under the action of the isoenzyme CYP3A4. It forms a number of metabolites, one of which, diacetylvinorelbine, retains antineoplastic activity.

Excretion

The mean terminal phase T_1/2 is 40 (27.7-43.6) h.

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 or severe hepatic impairment does not change.

The pharmacokinetics of vinorelbine does not depend on the age of the patients.

Indications

• Non-small cell lung cancer;
• Breast cancer;
• Hormone-resistant prostate cancer (in combination with low doses of oral corticosteroids).

ICD codes

Dosage Regimen

Velbin is used both as monotherapy and in combination with other antineoplastic drugs. When choosing the dose and administration regimen in each individual case, one should refer to the specialized literature.

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

For monotherapy, the usual dose of the drug is 25-30 mg/m² of body surface area once a 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 administration of the drug, the vein should be flushed by additionally administering at least 250 ml of 0.9% sodium chloride solution or 5% dextrose solution.

For patients with a body surface area >2 m², the single dose of Velbin for intravenous administration should not exceed 60 mg.

For polychemotherapy, the dose and frequency of Velbin administration depend on the specific anticancer therapy program.

If the neutrophil count decreases to <1500/µl or thrombocytopenia to <75,000/µl, the next administration of Velbin is postponed for 1 week. If it is necessary to withhold three weekly administrations of the drug due to hematological toxicity, it is recommended to discontinue the use of Velbin.

In patients with severe hepatic impairment, Velbin should be prescribed with caution at a dose not exceeding 20 mg/m².

Adverse Reactions

From the hematopoietic system: neutropenia, anemia, thrombocytopenia; against the background of bone marrow suppression – addition of secondary infections, fever (>38°C (100.4°F)), sepsis, septicemia, very rarely – complicated septicemia, in some cases leading to death. The lowest neutrophil count is observed on days 7-10 from the start of therapy, with recovery occurring within the next 5-7 days.

Cumulative hematotoxicity has not been noted.

Allergic reactions: rarely – anaphylactic shock or angioedema.

From the nervous system: paresthesia, hyperesthesia, decrease or loss of deep tendon reflexes, leg weakness, jaw pain, rarely severe paresthesia with sensory and motor symptoms, usually reversible.

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

From the respiratory system: shortness of breath, bronchospasm, interstitial pneumonia (with combination therapy with mitomycin C), acute respiratory distress syndrome.

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

From the skin and skin appendages: alopecia, skin rash.

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

Other: weakness, myalgia, arthralgia, fever, pain of various localization, including chest pain and pain in the tumor area, hyponatremia, hemorrhagic cystitis, and syndrome of inappropriate antidiuretic hormone secretion.

Contraindications

• Baseline blood neutrophil count <1500/µl, platelet count <75,000 /µl;
• Severe infectious diseases at the start of therapy or within the last 2 weeks;
• Severe hepatic impairment not associated with the tumor process;
• Need for constant oxygen therapy – in patients with lung tumor;
• Pregnancy;
• Lactation period (breastfeeding);
• Hypersensitivity to the components of the drug;
• Hypersensitivity to vinca alkaloids.

With caution, the drug should be used in cases of respiratory failure, bone marrow suppression (including after previous chemotherapy or radiation therapy), history of constipation or intestinal obstruction, history of neuropathy.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

During and for at least 3 months after discontinuation of therapy, reliable methods of contraception must be used.

Use in Hepatic Impairment

The pharmacokinetics of vinorelbine administered at a dose of 20 mg/m² weekly in patients with moderate or severe hepatic impairment does not change.

The drug is contraindicated in severe hepatic impairment not associated with the tumor process;

Use in Renal Impairment

In patients with severe hepatic impairment, Velbin should be prescribed with caution at a dose not exceeding 20 mg/m². In case of renal impairment, enhanced monitoring of the patient is necessary.

In case of severe hepatic impairment, the dose of Velbin should be reduced by 33%.

Geriatric Use

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

Special Precautions

Treatment with Velbin should be carried out under the supervision of a physician experienced in the use of antineoplastic drugs.

Treatment is carried out under strict hematological control, determining the number of leukocytes, neutrophils, platelets, and hemoglobin level before each subsequent injection or oral administration. If the neutrophil count is below 1500 cells/µl and/or platelets below 75,000 cells/µl, the next dose should be postponed until normal levels are restored.

In case of severe hepatic impairment, the dose of Velbin should be reduced by 33%.

In case of renal impairment, enhanced monitoring of the patient is necessary.

If signs of neurotoxicity of grade 2 or higher appear, the use of Velbin should be discontinued.

If shortness of breath, cough, or hypoxia of unknown etiology appears, the patient should be examined to exclude pulmonary toxicity.

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

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

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

Use in pediatrics

The safety and efficacy of Velbin in children have not been studied.

Overdose

Symptoms possible suppression of bone marrow function and manifestations of neurotoxicity.

Treatment a specific antidote is not known. In case of overdose, the patient should be hospitalized and vital functions should be carefully monitored. Symptomatic therapy should be carried out.

Drug Interactions

When used concomitantly with other cytostatics, mutual aggravation of side effects is possible, primarily myelosuppression.

When used concomitantly with mitomycin C, acute respiratory failure may develop.

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

Use during radiation therapy leads to radiosensitization. The use of vinorelbine after radiation therapy may lead to the reappearance of radiation reactions.

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

Storage Conditions

The drug should be stored at a temperature of 2 to 8°C (46.4°F).

Shelf Life

Shelf life – 18 months.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.