Vinorelbine (vinorelbine tartrate)

Dosage of vinorelbine tartrate is expressed in terms of the base.

Adjustment of vinorelbine dosage in geriatric patients solely on the basis of age is not necessary.

The effect of renal and/or hepatic impairment on the disposition of vinorelbine has not been fully established. Reduction of vinorelbine dosage in patients with renal impairment does not appear to be necessary.

Because the drug is extensively metabolized in the liver, doses of vinorelbine should be reduced and the drug should be administered with caution in patients with hepatic impairment. In patients with total serum bilirubin concentration of 2 mg/dL or less, no dosage reduction is required. In patients with total serum bilirubin concentration of 2.1-3 mg/dL, vinorelbine dose should be reduced to 50% of the starting dose. In patients with total serum bilirubin concentration exceeding 3 mg/dL, vinorelbine dose should be reduced to 25% of the starting dose. In patients with concurrent hepatic impairment and hematologic toxicity, vinorelbine dosage should be adjusted to the lower dosage advised by these guidelines.

Vinorelbine is administered only by IV injection into a free-flowing IV infusion or a large central vein, usually over a period of 6-10 minutes followed by flushing of the vein with a compatible IV solution, by individuals experienced in administration of the drug. The IV needle or catheter must be properly positioned before vinorelbine is injected. Improper administration of vinorelbine may result in extravasation of the drug causing local tissue necrosis and/or thrombophlebitis. Although vinorelbine also has been infused IV over 20-60 minutes via a peripheral vein or by rapid IV injection over 1-2 minutes, such methods of administration are not recommended because of the high rate of adverse local effects (e.g., phlebitis, erythema, venous discoloration, ulceration, pain) associated with this infusion rate and reports of severe back pain associated with rapid injection. Continuous IV infusions+ of vinorelbine have been well tolerated, but additional study is needed to establish the role of such infusion in treating various cancers.

Vinorelbine tartrate is very irritating and must not be given IM, subcutaneously, or intrathecally. Intrathecal administration of other vinca alkaloids (i.e., vinblastine, vincristine) has resulted in death. When dispensed, the syringe containing the individual dose prepared for administration to the patient must be labeled with the statement: ''Warning: For IV use only. Fatal if given intrathecally.'' The syringe must be enclosed in an overwrap (e.g., plastic bag or similar wrap with typed label) bearing the statements: ''Do not remove covering until moment of injection. Fatal if given intrathecally. For IV use only.''

In addition to the use of the warning labels and overwrap, other protective measures to prevent inadvertent intrathecal administration of vinorelbine or other vinca alkaloids include: administering diluted vinca alkaloid solutions in minibags, preparing the medication at the time of administration, attaching a unique filter, dispensing the vinca alkaloid separately from all other medications, dispensing the vinca alkaloid directly to the individual who is administering the drug, conducting an independent check of the dose and route of administration for the drug both at the time of preparation and prior to administration of the drug, and administering the vinca alkaloid in a separate room from rooms where other medications are administered.

Management of patients mistakenly receiving intrathecal vinorelbine is a medical emergency. Currently, there are no reports of patients mistakenly receiving intrathecal administration of vinorelbine. Unfortunately, the prognosis to date for patients inadvertently administered vincristine, another vinca alkaloid, intrathecally generally has been poor despite immediate efforts at removing spinal fluid and flushing with lactated Ringer's injection as well as other solutions, with such efforts failing to prevent ascending paralysis and death in almost all cases. In one case, progression of paralysis was stopped in an adult patient when the following treatment was initiated immediately after inadvertent intrathecal injection of vincristine. Such treatment consisted of immediate removal of as much CSF as safely possible via lumbar access, followed by flushing of the subarachnoid space with lactated Ringer's solution infused continuously at a rate of 150 mL/hour through a catheter in a cerebral lateral ventricle and removal of fluid through a lumbar access. As soon as available, fresh frozen plasma (25 mL) diluted in 1 L of lactated Ringer's solution was infused through the cerebral ventricular catheter at a rate of 75 mL/hour with removal of fluid through the lumbar access. The rate of infusion was adjusted to maintain a CSF protein concentration of 150 mg/dL. Glutamic acid was administered in a dose of 10 g given IV over 24 hours, followed by 500 mg orally 3 times daily for 1 month or until stabilization of neurologic status. The role of glutamic acid in this treatment is uncertain. There currently is no experience with this or any other treatment protocol in patients who mistakenly receive vinorelbine intrathecally.

Leakage of vinorelbine into surrounding tissue during IV administration of the drug can 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 administered into another vein. The manufacturer states that there are no established guidelines for the treatment of extravasation injuries caused by vinorelbine and that institutional guidelines for extravasation injuries may be used. (See Cautions: Local Effects.)

Vinorelbine for injection concentrate must be diluted prior to injection into a free-flowing IV infusion or a large central vein. The manufacturer recommends diluting the concentrate in a syringe with 5% dextrose injection or 0.9% sodium chloride injection to a final vinorelbine concentration of 1.5-3 mg/mL or in an IV bag with 5% dextrose injection, 0.9% sodium chloride injection, 0.45% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection, Ringer's injection, or lactated Ringer's injection to a final vinorelbine concentration of 0.5-2 mg/mL. The diluted solution of vinorelbine should then be administered over a period of 6-10 minutes into the side port closest to the IV bag of a free-flowing IV infusion or into a large central vein followed by flushing with at least 75-125 mL of 0.9% sodium chloride injection or 5% dextrose injection over a period of 10 minutes.

Caution should be exercised in handling and preparing solutions of vinorelbine. Because skin reactions may occur with accidental exposure to vinorelbine, the manufacturer recommends the use of latex gloves when handling the drug. If vinorelbine tartrate injection or a solution of the drug comes in contact with the skin or mucosa, the affected area should be washed immediately and thoroughly with soap and water. Care must be taken to avoid contact of vinorelbine tartrate solutions with the eyes since severe irritation of the eye has been reported with accidental exposure to another vinca alkaloid; if contact occurs, the eye should be flushed thoroughly with water immediately.

Vinorelbine tartrate injection or solutions of the drug should be inspected visually for particulate matter and/or discoloration prior to administration.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

No enhanced messaging available.

Vinorelbine can cause fetal toxicity when administered to pregnant women, but potential benefits from use of the drug may be acceptable in certain conditions despite the possible risks to the fetus. Vinorelbine has been shown to be embryotoxic and/or fetotoxic in mice and rabbits at single doses of 9 and 5.5 mg/m2, respectively (one-third and one-sixth the usual human dose). At doses that were not toxic to the pregnant animal, fetal weight was reduced and ossification was delayed. Vinorelbine and fluorouracil were administered to 3 women with breast cancer during the second or third trimester of pregnancy. The infants were delivered at 34, 37, and 41 weeks' gestation and no chemotherapy-related adverse effects were observed except for anemia in one infant, which occurred 21 days after delivery. There are no adequate and controlled studies to date using vinorelbine in pregnant women. Vinorelbine should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. When vinorelbine is administered during pregnancy or the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug.

It is not known whether vinorelbine is distributed in milk. Because many drugs are distributed in milk and because of the potential for serious adverse reactions to vinorelbine in nursing infants, nursing should be discontinued during vinorelbine therapy.

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