Dosing and uses of Navelbine (vinorelbine)
Adult dosage forms and strengths
injectable solution
- 10mg/mL
Non-small Cell Lung Carcinoma
Monotherapy: 30 mg/sq.meter IV over 6-10 minutes qWeek
Combo Therapy
- 25 mg/sq.meter IV qWeek with IV cisplatin 100 mg/sq.meter q4Weeks OR
- 30 mg/sq.meter IV qWeek with cisplatin 120 mg/sq.meter on Days 1 & 29 & then q6Weeks
Breast Cancer (Off-label)
20-30 mg/sq.meter qWeek, has been administered as IV infusion, slow (3-5 minutes) or rapid IV injection
Ovarian Cancer (Off-label)
25 mg/sq.meter q7Days
25-30 mg/sq/meter/day on days 1 & 8 of 21 day cycle
Administration
Dilute IV concentration 0.5-2 mg/mL
Infuse over 6-10 minutes to reduce toxicity
Other Information
Hematologic toxicity (Granulocyte Count)
- >1500 cells/cu. mm: 100 % of dose
- 1000-1499 cells/cu. mm: Decrease dose 50%
- < 1000 cells/cu mm: Do not administer
Hepatic Insufficiency (total bilirubin)
- <2 mg/dL: 100% of dose
- 2.1-3 mg/dL: Decrease dose 50%
- >3 mg/dL: Decrease dose 75%
Neurotoxicity
- Grade > 2: Discontinue
Pediatric dosage forms and strengths
Safety & efficacy not established
Navelbine (vinorelbine) adverse (side) effects
>10%
Leukopenia (92%)
Granulocytopenia (90%)
Anemia (83%)
Elev AST (67%)
Nausea (44%)
Asthenia (36%)
Constipation (35%)
Fatigue (27%)
Peripheral neuropathy (25%)
Vomiting (20%)
Anorexia (20%)
Stomatitis (20%)
Alopecia (12%)
1-10%
Dyspnea (7%)
Chest pain (5%)
Rash (5%)
SOB (3%)
Hemorrhagic cystitis (1%)
SIADH (1%)
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to diagnose and manage complications
The needle should be properly positioned in the vein before this product is injected. Leakage to surrounding tissue during IV administration may cause considerable irritation. Immediately discontinue the injection, and introduce any remaining portion of the dose into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage will help disperse the drug and may minimize the discomfort and possibility of cellulitis.
Intrathecal use may be fataL
Contraindications
Hypersensitivity
Acute bacterial infection, ANC <1000/cu.mm, intrathecal (IT) administration, intestinal obstruction, paralytic ileus, pregnancy, lactation
Cautions
Vesicant: moderate
Likely fatal if given intrathecally
Bone marrow depression, neuropathy, neuromuscular dz, neurotoxic agents, ototoxic agents, pulmonary dz, hepatic impairment, potential CYP3A4 intxns
Avoid extravasation
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Navelbine (vinorelbine)
Half-Life: 28-44 hr
Peak Plasma: 234-1160 ng/mL
Protein Bound: 80-92%
Vd: 25-40 L/kg
Metabolism: CYP3A isoenzymes
Metabolites: vinorelbine N-oxide, deacetylvinorelbine
Clearance: 0.97-1.26 L/hr/kg
Excretion
Feces: 46%
Urine: 18%
Mechanism of action
Semi-synthetic vinca alkaloid; inhibits mitosis at metaphase by depolymerizing microtubules
Administration
IV Incompatibilities
Y-site: acyclovir, allopurinol, aminophylline, amphotericin B, ampho B cholesteryl sulfate, ampicillin, cefazolin, cefoperazone, cefotetan, ceftriaxone, cefuroxime, co-trimoxazole, fluorouracil, furosemide, ganciclovir, methylprednisolone sodium succinate, mitomycin, piperacillin, sodium bicarbonate, thiotepa
IV Compatibilities
Solution: D5W, Ns
Y-site (partial list): buprenorphine, cisplatin, cyclophosphamide, diphenhydramine, gemcitabine, fluconazole, granisetron, hydromorphone, imipenem-cilastatin, lorazepam, meperidine, morphine, ondansetron, KCl, vancomycin, zidovudine
IV Preparation
May be diluted in syringe or bag
Syringe: dilute to 1.5-3 mg/mL in NS or D5W
IV Bag: dilute to 0.5-2 mg/mL in NS, 1/2NS, D5W, D5/½NS, LR or Ringer's
IV Administration
Vesicant
For IV use only; fatal if given intrathecally
Administer IV over 6-10 min through sidearm of free-flowing IV closest to IV bag
Then flush with 75-125 mL of one of the IV fluids
Extravasation Management
Mix 250 U hyaluronidase with 6 mL Ns
Inject hyaluronidase solution subcutaneously through 6 clockwise injections into infiltrated area using a 25-gauge needle
Change needle with each new injection
Elevate extremities
Apply heat immediately for 1 hr
Give QID for 3-5 days
Application of cold or hydrocortisone is contraindicated
Storage
Store intact vials under refrigeration protected from light
Diluted solution may be stored in polypropylene syringes for 24 hr under normal light at 5-30°C
