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Dosage Administration

Contents

  • Dosage and Administration
  • Dose Modifications for Hematologic Toxicity
  • Dose Modification for Hepatic Insufficiency
  • Dose Modification for Concurrent Hematologic Toxicity and Hepatic Insufficiency
  • Administration Precautions
  • Preparation for Administration
  • Administration Guidelines
  • Handling
  • Stability
  • Physical and Chemical Incompatibilities
  • How Supplied
  • Storage
  • Table 4. Compounds Found to be Physically Incompatible with NAVELBINE (vinorelbine tartrate) injection
  • Antibiotics
  • Antiviral Agents
  • Antineoplastic Agents
  • Miscellaneous

  • Dosage and Administration

    The usual initial dose of NAVELBINE (vinorelbine tartrate) Injection is 30 mg/square m administered weekly as a 6- to 10-minute intravenous injection. NAVELBINE dose modifications should be instituted in patients with hematologic toxicity or hepatic insufficiency. For patients experiencing both hematologic toxicity and hepatic impairment, the lowest dose calculated by the following schedules should be used. No dose adjustments are required for renal insufficiency. Treatment with NAVELBINE should be discontinued in patients experiencing moderate or severe neurotoxicity.


    Dose Modifications for Hematologic Toxicity

    Granulocyte counts should be equal to, or greater than1000 cells/cubic mm prior to the administration of NAVELBINE (vinorelbine tartrate) Injection. Adjustments in the dosage should be based on granulocyte counts obtained on the day of treatment according to Table 2.

    Table 2. Dose Modifications for Patients with Hematologic Toxicity
    Granulocyte Count*
    (cells/mm3)                                  Dose
    on Day of Treatment                          (mg/square m)
    
    equal to, or greater than 1500 30 1000 to 1499 15 less than 1000 Do not administer. Repeat granulocyte count in 1 week. If 3 consecutive weekly doses are held because granulocyte count is less than 1000 cells/cubic mm discontinue NAVELBINE.

    Note: For patients who, during treatment with NAVELBINE, have experienced fever and/or sepsis while granulocytopenic or had two (2) consecutive weekly doses held due to granulocytopenia, subsequent doses of NAVELBINE should be:

    22.5 mg/square m for granulocyte counts of equal to, or greater than 1500 cells/cubic mm
    11.25 mg/square m for granulocyte counts of 1000 to 1499 cells/cubic mm


    *The term "granulocytes" as used in clinical practice is usually synonymous with the terms "polys," "segs," "PMNs," and "neutrophils." In clinical trials, the NAVELBINE dosage was modified on the basis of the AGC on the day of therapy.

    The AGC is calculated as follows: total white blood cells (WBC) multiplied by the percent segmented plus banded neutrophils.

    Eg:
    WBC = 7000 cells/mm3 with a differential of 56% segs,
    9% bands, 30% lymphocytes, 2% eosinophils, 1% basophils, 2% monocytes then:
    AGC = 7000 x (0.56 + 0.09)
    AGC = 4550 cells/mm3

    Dose Modification for Hepatic Insufficiency


    NAVELBINE (vinorelbine tartrate) Injection should be administered with caution to patients with hepatic insufficiency. In patients who develop hyperbilirubinemia during treatment with NAVELBINE, the dose should be adjusted for total bilirubin according to Table 3.

    Table 3. Dose Modification Based on Total Bilirubin
     
    Total Bilirubin                                      Dose of NAVELBINE
    (mg/dL)	                                             (mg/m2)
    
    equal to or less than 2.0 30 2.1 to 3.0 15 less than 3.0 7.5


    Dose Modification for Concurrent Hematologic Toxicity and Hepatic Insufficiency

    In patients with both hematologic toxicity and hepatic insufficiency, the lower of the doses determined from Table 2 and Table 3 should be administered.


    Administration Precautions

    NAVELBINE (vinorelbine tartrate) Injection is a moderate vesicant and an irritant to the vein. Care must be taken to avoid extravasation during intravenous administration. Leakage into surrounding tissue during intravenous administration may cause considerable irritation, local tissue necrosis, and/or thrombophlebitis.

    It is extremely important that the intravenous needle or catheter be properly positioned in the vein before NAVELBINE is injected. To minimize the risk of venous irritation, diluted NAVELBINE should be infused into the side-arm port closest to the intravenous bag, not the patient. The intravenous site should be observed frequently during administration of NAVELBINE for patency, swelling, erythema, and pain during infusion and afterwards, as indicated.

    The patient should be instructed to immediately report any symptoms such as pain or stinging at the site of administration.

    Treating extravasation. If an extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Treat extravasation according to institutional guidelines.


    Preparation for Administration

    NAVELBINE (vinorelbine tartrate) Injection must be diluted in either a syringe or intravenous bag using Normal Saline, D5W or one of the compatible solutions listed below. The diluted drug may be used for up to 24 hours under normal light conditions when stored in polypropylene syringes or polyvinylchloride bags at 5 degrees; to 30 degrees C (41 degrees to 86 degrees F).

    Syringe. The calculated dose of NAVELBINE 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

    Intravenous bag. The calculated dose of NAVELBINE should be diluted to a concentration between 0.5 and 2.0 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% NaCl, USP
    Ringer's Injection, USP
    Lactated Ringer's Injection, USP


    Administration Guidelines

    1. Dilute NAVELBINE (vinorelbine tartrate) Injection in syringe or intravenous bag in Normal Saline, D5W or one of the other compatible solutions.
    2. Infuse diluted NAVELBINE intravenous over 6 to 10 minutes into side-arm port of free-flowing IV infusion, either peripherally or in central line. Be sure to infuse diluted NAVELBINE into the side-arm port closest to the free-flowing intravenous bag, not the patient.
    3. Flush vein with at least 75 to 125 mL of Normal Saline or D5W.

    Handling

    As with other toxic compounds, caution should be exercised in handling and preparing the solution of NAVELBINE. The use of gloves is recommended as a precaution against skin reactions that can occur with accidental exposure. If the NAVELBINE solution makes contact with the skin or mucosa, the affected area should be immediately washed with soap and water. Care should also be taken to avoid contact between NAVELBINE and the eye. Accidental contamination of the eye with another vinca alkaloid compound has been reported to result in severe irritation and it is likely that NAVELBINE has similar effects. If NAVELBINE comes into contact with the eye, the affected area should be flushed with water immediately and thoroughly.

    Procedures for the proper handling and disposal of anticancer drugs should be followed.[5-11]


    Stability


    Unopened vials of NAVELBINE (vinorelbine tartrate) Injection are stable until the date indicated on the package when stored under refrigeration at 2 degrees to 8 degrees C (36 degrees to 46 degrees F) and protected from light in the carton. Unrefrigerated, unopened vials of NAVELBINE are stable at temperatures up to 25 degrees C (77 degrees F) for up to 72 hours. The product should not be frozen.

    Diluted NAVELBINE may be used for up to 24 hours under normal light when stored at temperatures of 5 degrees to 30 degrees C (41 degrees to 86 degrees F).

    Physical and Chemical Incompatibilities


    Twenty of 92 agents tested have been found to be incompatible when mixed with NAVELBINE at high clinical concentrations in a 1:1 ratio (Table 4).[12]

    Mixtures of NAVELBINE and the compounds listed in Table 4 resulted in the formation of precipitates that ranged from slightly cloudy to cottony in appearance.

    To avoid problems with physically incompatible agents, it is recommended that either these agents be infused through separate lines or that the line be flushed thoroughly before infusion of an incompatible product is initiated. The extent of flushing depends on the type of intravenous line used, but 5 to 10 mL is typically sufficient. Administering incompatible agents sequentially without flushing is not sufficient to avoid precipitation problems, as some mixing will still occur inside the intravenous line.

    Some commonly used agents that are compatible with Navelbine (vinorelbine tartrate) Injection via Y-site administration include potassium chloride injection, antiemetics (chlorpromazine HCl, diphenhydramine HCl, hydroxyzine HCl, metoclopramide HCl, ondansetron HCl, and promethazine HCl), dexamethasone sodium phosphate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lorazepam, meperidine HCl, and morphine sulfate.


    How Supplied

    NAVELBINE is a clear colorless to pale yellow solution in Water for Injection containing 10 mg/mL vinorelbine. NAVELBINE is supplied in:

    Each vial is individually packaged in a carton. Multiple-use vials are not appropriate since NAVELBINE degrades in the presence of oxygen.


    Storage


    Vials containing NAVELBINE should be stored under refrigeration at 2 degrees to 8 degrees C (36 degrees to 46 degrees F) in the carton. Protect from light. DO NOT FREEZE.

    Unopened vials of NAVELBINE are stable until the date indicated on the package when stored under refrigeration at 2 degrees to 8 degrees C (36 degrees to 46 degrees F) and protected from light in the carton. Unrefrigerated vials of NAVELBINE are stable at temperatures up to 25 degrees C (77 degrees F) for up to 72 hours.

    Table 4. Compounds Found to be Physically Incompatible with NAVELBINE (vinorelbine tartrate) injection
     Drug                     Concentration     Description of
     Combined*                (mg/mL)           Physical Incompatibility
    
    When using NAVELBINE with the following compounds, administer sequentially followed by adequate flushing.
    Antibiotics
      amphotericin B**           0.6              Heavy yellow precipitate
                                                    formed immediately
      ampicillin sodium           20              Tiny particles formed
                                                    immediately, becoming large
                                                    white particles in
                                                    a cloudy solution
      cefoperazone sodium         40              Heavy white flocculent
                                                    precipitate formed immediately
      ceforanide                  20              Light haze formed immediately;
                                                    small amounts of particles 
                                                    formed in one sample in 4
                                                    hours
      cefotetan sodium            20              Tiny particles formed
                                                    immediately, becoming numerous
                                                    particles in a cloudy solution
                                                    in 4 hours
      ceftriaxone sodium          20              Tiny particles formed immediately,
                                                    becoming more numerous in 4
                                                    hours; total mean plus or minus
                                                    SD particle count increased
                                                    from 84 plus or minus 7 to
                                                    2801 plus or minus 139/mL;
                                                    10-micro m particles increased
                                                    from 5.7 plus or minus 2.1 to
                                                    46.0 plus or minus 7.0/mL;
                                                    25-micro m particles increased
                                                    from 1 in 3 mL to 3.0 plus or
                                                    minus 1.0/mL
      piperacillin sodium        40               Heavy white turbidity formed
                                                    immediately, becoming a white
                                                    flocculent precipitate in 4
                                                    hours
     trimethoprim/            0.8/4               Heavy white turbidity formed
       sulfamethoxazole                             immediately, developing into
                                                    particles in 1 hour
    
    Antiviral Agents
     Drug                     Concentration     Description of
     Combined*                (mg/mL)           Physical Incompatibility
    
    acyclovir sodium 7 Heavy white precipitate formed immediately ganciclovir sodium 20 White turbid solution with precipitate formed immediately
    Antineoplastic Agents
     Drug                     Concentration     Description of
     Combined*                (mg/mL)           Physical Incompatibility
    
    fluorouracil 16 Heavy white precipitate formed immediately mitomycin 0.5 Color changed from pale blue to reddish purple in 1 hour; became turbid (approximately 8.3 nephelometric turbidity units) and developed small amount of fine particles thiotepa 1 Cloudy solution with particles formed immediately
    Miscellaneous
     Drug                     Concentration     Description of
     Combined*                (mg/mL)           Physical Incompatibility
    
    aminophylline 2.5 Initial very light haze became visible in room light, along with large particles, in 1 hour furosemide 3 Heavy white precipitate formed immediately methylprednisolone 5 Heavy white precipitate formed sodium succinate immediately sodium bicarbonate 1*** Tiny particles and light blue haze formed immediately, developing into large particles in 4 hours
    * Tested in 0.9% Sodium Chloride Injection, USP, unless noted otherwise.
    ** Tested in both 0.9% Sodium Chloride Injection, USP, and 5% Dextrose Injection, USP.
    *** Milliequivalents per milliliter.

    Originally published in Trissel LA, Martinez JF, in Visual, Turbidimetric, and Particle-Content Assessment of Compatibility of Vinorelbine Tartrate with Selected Drugs During Simulated Y-Site Injection. Am J Hosp Pharm. 1994;51:495-499. 1994, American Society of Hospital Pharmacists, Inc. All rights reserved. Adapted with permission. (R9458)

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