DOSAGE AND ADMINISTRATION
Single-Agent Vinorelbine: The usual initial dose of single-agent Vinorelbine is 30 mg/m2 administered weekly. The recommended method of administration is an intravenous injection over 6 to 10 minutes. In controlled trials, single-agent Vinorelbine was given weekly until progression or dose-limiting toxicity.
Vinorelbine in Combination with Cisplatin: Vinorelbine may be administered weekly at a dose of 25 mg/m2 in combination with cisplatin given every 4 weeks at a dose of 100 mg/m2.
Blood counts should be checked weekly to determine whether dose reductions of Vinorelbine and/or cisplatin are necessary. In the SWOG study, most patients required a 50% dose reduction of Vinorelbine at day 15 of each cycle and a 50% dose reduction of cisplatin by cycle 3.
Vinorelbine may also be administered weekly at a dose of 30 mg/m2 in combination with cisplatin, given on days 1 and 29, then every 6 weeks at a dose of 120 mg/m2.
Dose Modifications for Vinorelbine: The dosage should be adjusted according to hematologic toxicity or hepatic insufficiency, whichever results in the lower dose for the corresponding starting dose of Vinorelbine (see Table 5).
Dose Modifications for Hematologic Toxicity: Granulocyte counts should be ≥1,000 cells/mm3 prior to the administration of Vinorelbine. Adjustments in the dosage of Vinorelbine should be based on granulocyte counts obtained on the day of treatment according to Table 5.
Table 5. Dose Adjustments Based on Granulocyte Counts |
Granulocytes on Day of Treatment (cells/mm3)
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Percentage of Starting Dose of Vinorelbine
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> 1,500
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100%
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1,000 to 1,499
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50%
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<1,000
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Do not administer. Repeat granulocyte count in 1 week. If 3 consecutive weekly doses are held because granulocyte count is <1,000 cells/mm3, discontinue Vinorelbine.
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Note: For patients who, during treatment with Vinorelbine, experienced fever and/or sepsis while granulocytopenic or had 2 consecutive weekly doses held due to granulocytopenia, subsequent doses of Vinorelbine should be:
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> 1,500
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75%
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1,000 to 1,499
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37.5%
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<1,000
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See above
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Dose Modifications for Hepatic Insufficiency: Vinorelbine should be administered with caution to patients with hepatic insufficiency. In patients who develop hyperbilirubinemia during treatment with Vinorelbine, the dose should be adjusted for total bilirubin according to Table 6.
Table 6. Dose Modification Based on Total Bilirubin |
Total Bilirubin
(mg/dL)
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Percentage of Starting Dose of Vinorelbine
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< 2.0
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100%
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| |
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2.1 to 3.0
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50%
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>3.0
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25%
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Dose Modifications for Concurrent Hematologic Toxicity and Hepatic Insufficiency: In patients with both hematologic toxicity and hepatic insufficiency, the lower of the doses based on the corresponding starting dose of Vinorelbine determined from Table 5 and Table 6 should be administered.
Dose Modifications for Renal Insufficiency: No dose adjustments for Vinorelbine are required for renal insufficiency. Appropriate dose reductions for cisplatin should be made when Vinorelbine is used in combination.
Dose Modifications for Neurotoxicity: If Grade ≥2 neurotoxicity develops, Vinorelbine should be discontinued.
Administration Precautions: Caution - Vinorelbine must be administered intravenously. It is extremely important that the intravenous needle or catheter be properly positioned before any Vinorelbine is injected. Leakage into surrounding tissue during intravenous administration of Vinorelbine may cause considerable irritation, local tissue necrosis, and/or thrombophlebitis. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Since there are no established guidelines for the treatment of extravasation injuries with Vinorelbine, institutional guidelines may be used. The ONS Chemotherapy Guidelines provide additional recommendations for the prevention of extravasation injuries.1
As with other toxic compounds, caution should be exercised in handling and preparing the solution of Vinorelbine. Skin reactions may occur with accidental exposure. The use of gloves is recommended. If the solution of Vinorelbine contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water. Severe irritation of the eye has been reported with accidental contamination of the eye with another vinca alkaloid. If this happens with Vinorelbine, the eye should be flushed with water immediately and thoroughly.
Procedures for proper handling and disposal of anticancer drugs should be used. Several guidelines on this subject have been published.2-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Vinorelbine Injection is a clear, colorless to pale yellow solution. Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. If particulate matter is seen, Vinorelbine should not be administered.
Preparation for Administration: Vinorelbine Injection must be diluted in either a syringe or IV bag using one of the recommended solutions. The diluted Vinorelbine should be administered over 6 to 10 minutes into the side port of a free-flowing IV closest to the IV bag followed by flushing with at least 75 to 125 mL of one of the solutions. Diluted Vinorelbine may be used for up to 24 hours under normal room light when stored in polypropylene syringes or polyvinyl chloride bags at 5° to 30°C (41° to 86°F).
Syringe: The calculated dose of Vinorelbine should be diluted to a concentration between 1.5 and 3.0 mg/mL. The following solutions may be used for dilution:
5% Dextrose Injection, USP
0.9% Sodium Chloride Injection, USP
IV Bag: The calculated dose of Vinorelbine should be diluted to a concentration between 0.5 and 2 mg/mL. The following solutions may be used for dilution:
5% Dextrose Injection, USP
0.9% Sodium Chloride Injection, USP
0.45% Sodium Chloride Injection, USP
5% Dextrose and 0.45% Sodium Chloride Injection, USP
Ringer’s Injection, USP
Lactated Ringer’s Injection, USP
Stability: Unopened vials of Vinorelbine are stable until the date indicated on the package when stored under refrigeration at 2° to 8°C (36° to 46°F) and protected from light in the carton.
Unopened vials of Vinorelbine are stable at temperatures up to 25°C (77°F) for up to 72 hours.
This product should not be frozen.
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