No

Antineoplastic Agent, Natural Source (Plant) Derivative

Treatment of nonsmall cell lung cancer (as a single agent or in combination with cisplatin)

D

For I.V. use only; I.T. use may result in death; severe bone marrow suppression (granulocyte counts <1000 cells/mm³) or presence of bacterial infection not under control prior to initiation of therapy

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Avoid extravasation; dosage modification required in patients with impaired liver function and neurotoxicity. Frequently monitor patients for myelosuppression both during and after therapy. Granulocytopenia is dose-limiting. Intrathecal administration may result in death. Use with caution in patients with cachexia or ulcerated skin.

>10%:

Dermatologic: Alopecia (12%)

Gastrointestinal: Nausea and vomiting are most common and are easily controlled with standard antiemetics; constipation, diarrhea, stomatitis, abdominal cramps, anorexia, metallic taste

Emetic potential: Moderate (30% to 60%)

Hematologic: May cause severe bone marrow suppression and is the dose-limiting toxicity of vinorelbine; severe granulocytopenia may occur following the administration of vinorelbine

Myelosuppressive:

WBC: Moderate - severe

Onset (days): 4-7

Nadir (days): 7-10

Recovery (days): 14-21

Neuromuscular and skeletal: Peripheral neuropathy (20% to 25%)

1% to 10%:

Central nervous system: Fatigue

Extravasation: Vesicant and can cause tissue irritation and necrosis if infiltrated; if extravasation occurs, follow institutional policy, which may include hyaluronidase and hot compresses

Vesicant chemotherapy

Neuromuscular & skeletal: Mild to moderate peripheral neuropathy manifested by paresthesia and hyperesthesia, loss of deep tendon reflexes; myalgia, arthralgia, jaw pain

<1%: Hemorrhagic colitis, severe peripheral neuropathy (generally reversible)

Symptoms of overdose include bone marrow suppression, mental depression, paresthesia, loss of deep reflexes, neurotoxicity. Overdoses involving quantities of up to 10 times the recommended dose (30 mg/m²) have been reported. The toxicities described were consistent with those listed in the adverse reactions section including paralytic ileus, stomatitis, and esophagitis. Bone marrow aplasia, sepsis, and paresis have also been reported. Fatalities have occurred following overdose of vinorelbine.

There are no antidotes for vinorelbine. Treatment is supportive and symptomatic, including fluid restriction or hypertonic saline (3% sodium chloride) for drug-induced secretion of inappropriate antidiuretic hormone (SIADH), diazepam or phenytoin for seizures, laxatives for constipation, blood transfusions, growth factors, antibiotics, and antiemetics for toxic emesis.

CYP2D6 enzyme inhibitor

Previous or simultaneous use with mitomycin-C has resulted in acute shortness of breath and severe bronchospasm within minutes or several hours after vinca alkaloid injection and may occur up to 2 weeks after the dose of mitomycin

Cisplatin: Incidence of granulocytopenia is significantly higher than with single-agent vinorelbine

Store intact vials under refrigeration (2°C to 8°C) and protect from light; vials are stable at room temperature for up to 72 hours

Further dilution in D₅W or NS is stable for 24 hours at room temperature

Standard I.V. dilution:

I.V. push: Dose/syringe (concentration = 1.5-3 mg/mL)

Maximum syringe size for IVP is a 30 mL syringe and syringe should be less than or equal to 75% full

IVPB: Dose/50-250 mL D₅W or NS (concentration = 0.5-2 mg/mL)

Solutions are stable for 24 hours at room temperature

Semisynthetic vinca alkaloid which binds to tubulin and inhibits microtubule formation, therefore, arresting the cell at metaphase by disrupting the formation of the mitotic spindle; it is specific for the M and S phases; binds to microtubular protein of the mitotic spindle causing metaphase arrest

Absorption: Not reliably absorbed from the GI tract and must be given I.V.

Distribution: V_d: 25.4-40.1 L/kg; binds extensively to human platelets and lymphocytes (79.6% to 91.2%)

Metabolism: Extensive hepatic metabolism to an active metabolite (deacetylvinorelbine)

Half-life (triphasic): Terminal: 27.7-43.6 hours; Mean plasma clearance: 0.97-1.26 L/hour/kg

Elimination: Feces (46%) and urine (18%)

Refer to individual protocols; varies depending upon clinical and hematological response

Dosage adjustment in hematological toxicity: Granulocyte counts should be greater than or equal to 1000 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 as follows:

Granulocytes greater than or equal to 1500 cells/mm³ on day of treatment: Administer 30 mg/m²

Granulocytes 1000-1499 cells/mm³ on day of treatment: Administer 15 mg/m²

Granulocytes <1000 cells/mm³ on day of treatment: Do not administer. Repeat granulocyte count in one week; if 3 consecutive doses are held because granulocyte count is <1000 cells/mm³, discontinue vinorelbine

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

22.5 mg/m² for granulocytes greater than or equal to 1500 cells/mm³

11.25 mg/m² for granulocytes 1000-1499 cells/mm³

Dosage adjustment in renal impairment: No dose adjustments are required for renal insufficiency. If moderate or severe neurotoxicity develops, discontinue vinorelbine.

Dosing adjustment in hepatic impairment: Vinorelbine should be administered with caution in patients with hepatic insufficiency. In patients who develop hyperbilirubinemia during treatment with vinorelbine, the dose should be adjusted for total bilirubin as follows:

Serum bilirubin less than or equal to 2 mg/dL: Administer 30 mg/m²

Serum bilirubin 2.1-3 mg/dL: Administer 15 mg/m²

Serum bilirubin >3 mg/dL: Administer 7.5 mg/m²

Dosing adjustment in patients with concurrent hematologic toxicity and hepatic impairment: Administer the lower doses determined from the above recommendations

CBC with differential and platelet count, serum uric acid, hepatic function tests

May cause drowsiness

Bone marrow suppression is common; avoid clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered by infusion, usually on a cyclic basis. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition (small frequent meals will help). You will most likely loss your hair (will grow back after therapy); experience nausea or vomiting (request medication); feel weak or lethargic (use caution when driving or engaging in tasks requiring alertness until response to drug is known). Use good oral care to reduce incidence of mouth sores. You will be more susceptible to infection; avoid crowds or exposure to infection. Report weakness, skeletal pain, or tremors; signs of infection (eg, fever, chills, sore throat, burning urination, fatigue); unusual bleeding (eg, tarry stools, easy bruising, blood in stool, urine, or mouth); numbness, pain, or tingling of fingers or toes; unresolved mouth sores; skin rash or itching; uncontrolled nausea, vomiting, or abdominal pain; or difficulty breathing. Pregnancy/breast-feeding precautions: Do not get pregnant or breast-feed.

Extravasation treatment:

Mix 250 units hyaluronidase with 6 mL of NS

Inject the hyaluronidase solution subcutaneously through 6 clockwise injections into the infiltrated area using a 25-gauge needle; change the needle with each new injection

Apply heat immediately for 1 hour; repeat 4 times/day for 3-5 days

Application of cold or hydrocortisone is contraindicated.

Monitor for life-threatening bronchospasm (most likely to occur if patient is also taking mitomycin). Maintain adequate hydration; allopurinol may be given to prevent uric acid nephropathy; may cause sloughing upon extravasation.

Injection, as tartrate: 10 mg/mL (1 mL, 5 mL)

Budman DR, "Vinorelbine (Navelbine®): A Third-Generation Vinca Alkaloid," Cancer Invest, 1997, 15(5);475-90.

Johnson SA, Harper P, Hortobagyi GN, et al, "Vinorelbine: An Overview," Cancer Treat Rev, 1996, 22(2):127-42.

Jones SF and Burris HA 3d, "Vinorelbine: A New Antineoplastic Drug for the Treatment of Nonsmall Cell Lung Cancer," Ann Pharmacother, 1996, 30(5):501-6.

LeVeque D and Jehl F, "Clinical Pharmacokinetics of Vinorelbine," Clin Pharmacokinet, 1996, 31(3):184-97.

Toso C and Lindley C, "Vinorelbine: A Novel Vinca Alkaloid," Am J Health Syst Pharm, 1995, 52(12):1287-304.