Overview
11 DESCRIPTION Vinorelbine Injection, USP contains vinorelbine, a semi-synthetic vinca alkaloid. The molecular formula for vinorelbine tartrate is C 45 H 54 N 4 O 8 •2C 4 H 6 O 6. It has a molecular weight of 1079.11. The structural formula is as follows: Vinorelbine tartrate is a white to light yellow amorphous powder.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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 Ca++-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 40 μM, suggesting a modest selectivity of vinorelbine for mitotic microtubules. 12.
Indications
- 1 INDICATIONS AND USAGE Vinorelbine Injection is indicated: In combination with cisplatin for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) As a single agent for the treatment of patients with metastatic NSCLC Vinorelbine Injection is a vinca alkaloid indicated: In combination with cisplatin for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) ( 1 ) As a single agent for first-line treatment of patients with metastatic NSCLC ( 1 )
Common Doses
- 30 mg
- 100 mg
- 25 mg
- 120 mg
Dosage
2 DOSAGE AND ADMINISTRATION In combination with cisplatin: 25 to 30 mg/m 2 as an intravenous injection or infusion once weekly ( 2.1 ) Single agent: 30 mg/m 2 as intravenously once a week ( 2.1 ) Adjust dose in patients with decreased neutrophil counts or elevated serum total bilirubin ( 2.2 ) 2.1 Recommended Dosage In Combination with Cisplatin 100 mg/m 2 The recommended dosage of Vinorelbine Injection is 25 mg/m 2 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/m 2 on Day 1 only of each...
Black Box Warning
WARNING: MYELOSUPPRESSION Severe myelosuppression resulting in serious infection, septic shock, hospitalization and death can occur [see Warnings and Precautions ( 5.1 )]. Decrease the dose or withhold vinorelbine in accord with recommended dose modifications [see Dosage and Administration ( 2.2 )]. WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. Severe myelosuppression resulting in serious infection, septic shock, and death can occur ( 5.1 ). Decrease the dose or withhold vinorelbine in accord with recommended dose modifications ( 2.2 ).
Contraindications
- 4 CONTRAINDICATIONS None None
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions ( 5.1 )] Hepatic Toxicity [see Warnings and Precautions ( 5.2 )] Severe Constipation and Bowel Obstruction [see Warnings and Precautions ( 5.3 )] Extravasation and Tissue Injury [see Warnings and Precautions ( 5.4 )] Neurologic Toxicity [see Warnings and Precautions ( 5.5 )] Pulmonary Toxicity and Respiratory Failure [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Inhibitors of CYP3A4: May cause earlier onset and/or increased severity of adverse reactions ( 7.1 ) 7.1 CYP3A Inhibitors Exercise caution in patients concurrently taking drugs known to inhibit CYP3A. Concurrent administration of vinorelbine with a CYP3A inhibitor may cause an earlier onset and/or an increased severity of adverse reactions.