Navelbine^® (Capsules, 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

Antineoplastic agent from the group of cytostatics, 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 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 the capsules orally on days 1 and 5 of a 21-day cycle, or weekly. The typical weekly dose is 60-80 mg/m². Swallow the capsules whole with a full glass of water during a meal.

For the concentrate for solution, administer intravenously once weekly. The standard single dose is 25-30 mg/m². Dilute the concentrate in a sufficient volume of compatible solution, such as 0.9% sodium chloride or 5% glucose, to a final concentration of 1.5-3.0 mg/mL.

Infuse the diluted solution intravenously over 6-10 minutes. Follow the infusion with at least 250-500 mL of a compatible flushing solution to reduce the risk of phlebitis.

Before each administration, mandatorily assess the complete blood count. Withhold therapy if the absolute neutrophil count (ANC) is below 1500 cells/µL or platelets are below 100,000 cells/µL. Resume treatment only after hematological recovery.

Reduce the dose by 50% for patients with severe hepatic impairment (bilirubin > 2-3 times the upper limit of normal). No initial dose adjustment is required for renal impairment.

Adjust subsequent doses based on hematological tolerance and the severity of non-hematological toxicity observed after the previous cycle. Permanently discontinue for the development of severe neuropathy.

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 long-term 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 liver dysfunction.

Use in Renal Impairment

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

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 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.

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.