VIinorelbine Kelun-Kazpharm (Concentrate) Instructions for Use

Marketing Authorization Holder

Kelun-Kazpharm, LLP (Kazakhstan)

ATC Code

L01CA04 (Vinorelbine)

Active Substance

Vinorelbine (Rec.INN registered by WHO)

Dosage Form

Vinorelbine Kelun-Kazpharm

Concentrate for solution for infusion 10 mg/ml: 1 ml or 5 ml fl. 1 pc.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion in the form of a transparent solution from colorless to pale yellow.

Excipients : water for injections – up to 1 ml.

1 ml – vials of colorless glass (type I) (1) – cardboard packs.
5 ml – vials of colorless glass (type I) (1) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent – alkaloid

Pharmacological Action

Antineoplastic agent from the group of cytostatics, is a semi-synthetic derivative of one of the alkaloids of the periwinkle plant – 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, 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 h. Systemic clearance is 1.3 L/h/kg. It is excreted mainly with 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

Determine the dosage individually based on the specific cancer type, disease stage, patient’s general condition, and the chosen anticancer therapy protocol.

Administer as an intravenous infusion. Dilute the concentrate before administration using a 0.9% sodium chloride solution or a 5% glucose solution.

Calculate the single dose based on body surface area. The typical monotherapy dose for adults is 25-30 mg/m². Administer the infusion at this dose once weekly.

For combination chemotherapy regimens, adjust the vinorelbine dose accordingly, often to a lower range of 20-25 mg/m² administered weekly.

Before each administration, mandatorily check the complete blood count. Do not administer if the absolute neutrophil count is below 1500 cells/µl or if the platelet count is below 100,000 cells/µl.

Withhold therapy if granulocyte count is less than 2000/µl. Resume treatment only after hematological recovery to a safe level.

Reduce the dose by 50% for patients with severe hepatic impairment (total bilirubin greater than 2-3 times the upper limit of normal).

Administer the diluted solution as a short intravenous infusion over 6-10 minutes. Following the infusion, flush the vein with a sufficient volume of saline.

Avoid extravasation rigorously. Monitor the injection site for signs of infiltration, which can cause severe local tissue damage, pain, and necrosis.

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 intestinal obstruction.

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 insufficiency; concomitant use with strong inhibitors or inducers of the CYP3A4 isoenzyme, vitamin K antagonists, with macrolides, cobicistat, protease inhibitors, lapatinib; patients from the 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

The increased toxic effect 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 treatment with 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 is not performed, postponing it until a safe level of granulocytes is reached.

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

Radiation therapy 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.