Vinorelbine Tartrate is indicated for:

• First-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with cisplatin.
• Treatment of metastatic NSCLC as a single-agent therapy.

Vinorelbine is a vinca alkaloid that interferes with microtubule assembly. The antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinorelbine may also interfere with: 1) amino acid, cyclic AMP and glutathione metabolism, 2) calmodulin-dependent Ca²⁺ transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis. Vinorelbine inhibited mitotic microtubule formation in intact mouse embryo tectal plates at a concentration of 2 μM, inducing a blockade of cells at metaphase, but produced depolymerization of axonal microtubules at a concentration of 40 μM, suggesting a modest selectivity of vinorelbine for mitotic microtubules.

In Combination with Cisplatin 100 mg/m2: The recommended dosage of Vinorelbine Tartrate is 25 mg/m2 administered as an intravenous injection or infusion over 6 to 10 minutes on Days 1, 8, 15 and 22 of a 28-day cycle in combination with cisplatin 100 mg/m2 on Day 1 only of each 28-day cycle.

In Combination with Cisplatin 120 mg/m2: The recommended dosage of Vinorelbine Tartrate is 30 mg/m2 administered as an intravenous injection or infusion over 6 to 10 minutes once a week in combination with cisplatin 120 mg/m2 on Days 1 and 29, then every 6 weeks.

Single Agent: The recommended dosage of Vinorelbine Tartrate is 30 mg/m2 administered intravenously over 6 to 10 minutes once a week.

Pediatric Use: The safety and effectiveness of Vinorelbine Tartrate in pediatric patients have not been established.

Caution is required when Vinorelbine Tartrate is used together with drugs that inhibit CYP3A enzymes. Such combinations may lead to an earlier onset or increased severity of adverse effects.

Hypersensitivity to vinorelbine or other vinca alkaloids; severe current or recent infection (within the last 2 weeks); neutropenia; thrombocytopenia; severe hepatic impairment. Intrathecal administration. Do not give concomitantly with radiotherapy if the liver is in the treatment field. Pregnancy, lactation.

Most common adverse reactions (incidence ≥20%) are leukopenia, neutropenia, anemia, increased aspartate aminotransferase, nausea, vomiting, constipation, asthenia, injection site reaction and peripheral neuropathy.

Based on findings from animal studies and its mechanism of action, Vinorelbine Tartrate can cause fetal harm when administered to a pregnant woman. Available human data are insufficient to inform the drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies in mice and rabbits, embryo and fetal toxicity were observed with administration of vinorelbine at doses approximately 0.33 and 0.18 times the human therapeutic dose, respectively. Advise pregnant women of the potential risk to a fetus.

There are no data on the presence of vinorelbine in human milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from vinorelbine, advise women not to breastfeed during treatment with Vinorelbine Tartrate and for 9 days after the final dose.

Hepatic Toxicity: Monitor hepatic function prior to initiation and during treatment.

Severe constipation and bowel obstruction, including necrosis and perforation, occur. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction and/or paralytic ileus.

Extravasation can result in severe tissue injury, local tissue necrosis and/or thrombophlebitis. Immediately stop Vinorelbin and institute recommended management procedures.

Neurologic Toxicity: Severe sensory and motor neuropathies occur. Monitor patients for new or worsening signs and symptoms of neuropathy. Discontinue for Grade 2 or greater neuropathy.

Pulmonary toxicity and respiratory failure occur. Interrupt Vinorelbin in patients who develop unexplained dyspnea or have any evidence of pulmonary toxicity. Permanently discontinue for confirmed interstitial pneumonitis or ARDS.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception

Cytotoxic chemotherapy

Store vials at 2°C–8°C in the original carton and protect from light. Do not freeze. Unopened vials may remain stable at 25°C for up to 72 hours. Diluted solutions should be stored at 5°C–30°C.