Vinorelbin (Concentrate) Instructions for Use

ATC Code

L01CA04 (Vinorelbine)

Active Substance

Vinorelbine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agents; plant alkaloids and other natural substances; vinca alkaloids and their analogues

Pharmacological Action

An antineoplastic agent from the group of cytostatics, it is a semi-synthetic derivative of one of the alkaloids of the pink periwinkle – vinblastine. Like vinblastine, Vinorelbine blocks cell mitosis at the metaphase stage by binding to the protein tubulin.

Pharmacokinetics

After intravenous administration, Vinorelbine is widely distributed in tissues; the V_d is more than 40 L/kg. Binding to plasma proteins is moderate – 13.5%, to platelets – high – 78%.

The kinetics of vinorelbine in plasma is triphasic. The mean T_1/2 of the active substance in the terminal phase is 40 hours. Systemic clearance is 1.3 L/h/kg. It is excreted primarily in the bile.

Indications

Non-small cell lung cancer, advanced breast cancer, hormone-resistant prostate cancer (in combination with low-dose oral corticosteroid therapy).

ICD codes

Dosage Regimen

Administer Vinorelbin concentrate only by intravenous route as a short infusion. Do not administer intrathecally; fatal outcomes have been reported.

Determine the dose individually based on body surface area, typically 25-30 mg/m². Administer once weekly. Calculate the exact dose immediately before preparation.

Dilute the concentrate with a compatible solution, such as 0.9% sodium chloride or 5% glucose, to a final concentration of 1.5-3.0 mg/mL. Administer the diluted solution over 6-10 minutes.

Follow administration with a flush of at least 75-125 mL of the compatible solution to minimize vascular irritation.

Assess the complete blood count with differential prior to each weekly dose. Withhold the dose if the granulocyte count is below 2000 cells/µL or if the platelet count is below 100,000 cells/µL.

Resume treatment only after hematological recovery. For grade 4 neutropenia or thrombocytopenia, consider a dose reduction of 50% for subsequent cycles.

Reduce the dose by 50% in patients with total bilirubin levels between 2 and 3 mg/dL. Do not administer if the total bilirubin exceeds 3 mg/dL.

Monitor for signs of extravasation during infusion. If extravasation occurs, stop administration immediately and institute appropriate management measures for vesicant injury.

Adverse Reactions

From the hematopoietic system: granulocytopenia, anemia.

From the peripheral nervous system: possible decrease (up to complete extinction) of osteotendinous reflexes; rarely – paresthesia; with prolonged use – increased fatigue of the muscles of the lower extremities.

From the digestive system: nausea, less often – vomiting; due to the effect of the drug on the autonomic innervation of the intestine – constipation; in some cases – intestinal paresis; rarely – paralytic ileus.

Allergic reactions: difficulty breathing, bronchospasm; in isolated cases – skin reactions.

Other: alopecia, jaw pain.

Local reactions: phlebitis.

Contraindications

Baseline absolute neutrophil count <1500 cells/µL, baseline platelet count <100000 cells/µL; infectious diseases on the day of therapy initiation or suffered within the last 2 weeks; concomitant use with yellow fever vaccine; pregnancy, breastfeeding period; children and adolescents under 18 years of age, hypersensitivity to vinorelbine.

With caution

Patients with a history of coronary artery disease, severe general condition of patients, severe hepatic impairment; concomitant use with strong inhibitors or inducers of the CYP3A4 isoenzyme, vitamin K antagonists, with macrolides, cobicistat, protease inhibitors, lapatinib; patients of Japanese population (due to more frequent cases of interstitial lung disorders in this category of patients).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in severe hepatic impairment.

Use in Renal Impairment

Due to low renal elimination, dose adjustment is not required in patients with renal impairment.

Pediatric Use

Contraindicated for use in children and adolescents.

Geriatric Use

Increased toxic effects of vinorelbine in elderly patients cannot be completely ruled out.

Special Precautions

Treatment with vinorelbine should be carried out only in a specialized hospital by personnel experienced in the use of chemotherapeutic agents. Before starting treatment, as well as before each subsequent administration of vinorelbine, it is necessary to monitor the composition of peripheral blood. If the granulocyte count is less than 2000/µL, the next injection should not be given, postponing it until a safe granulocyte level is reached.

Vinorelbine should be used with caution in patients with impaired liver function; in this case, the dose should be reduced.

Radiotherapy to the liver area should not be prescribed during treatment with vinorelbine.

Avoid extravasation during intravenous infusion. The entry of vinorelbine into the tissues surrounding the vein leads to pain, inflammation, and in severe cases, necrosis.

Avoid contact of vinorelbine solution with the eyes.

Drug Interactions

With simultaneous use with mitomycin C, the risk of respiratory depression and bronchospasm increases, especially in predisposed patients; with cisplatin – an increase in the frequency of toxic reactions.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.