vinorelbine (Rx)

>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%)

Postmarketing Reports

Palmar-plantar erythrodysesthesia syndrome

Hepatic toxicity

Bowel obstruction

Pulmonary toxicity

Respiratory failure

Contraindications

None

Cautions

Myelosuppression, manifested by neutropenia, anemia, and thrombocytopenia reported; neutropenia is the major dose-limiting toxicity; monitor complete blood counts before each dose

Risk of extravasation and tissue injury

Sensory and motor neuropathies reported

Can cause fetal harm if administered to pregnant women based on findings from animal studies and mechanism of action

Hepatic toxicity

• Drug-induced liver injury manifested by elevated aspartate aminotransferase (AST) and bilirubin occur in patients receiving drug as single agent and in combination with cytotoxic agents
• Assess hepatic function prior to initiation of therapy and periodically during treatment
• Reduce dose for patients who develop elevations in total bilirubin greater than or equal to 2 times upper limit of normal

Gastrointestinal effects

• Severe and fatal paralytic ileus, constipation, intestinal obstruction, necrosis, and perforation reported
• Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction and/or paralytic ileus
• Consider adequate dietary fiber intake, hydration and routine use of stool softeners

Pulmonary toxicity

• Pulmonary toxicity, including severe acute bronchospasm, interstitial pneumonitis, acute respiratory distress syndrome (ARDS) occur in patients receiving therapy
• Interrupt therapy in patients who develop unexplained dyspnea or have any evidence of pulmonary toxicity
• Permanently discontinue therapy for confirmed interstitial pneumonitis or ARDS

Preparation in IV infusion bag only

• On January 15, 2021, FDA alerted that vinca alkaloids should be prepared in IV infusion bags only
• Intrathecal (IT) administration will result in severe neurological injury and/or death
• Label update is to reduce the potential for unintended IT administration

Pregnancy

Based on animal findings, can cause fetal harm when administered to pregnant women

Verify pregnancy status in females of reproductive potential before initiating

Animal studies

• In animal reproduction studies in mice and rabbits, embryo and fetal toxicity were observed with vinorelbine doses ~0.33 and 0.18 times the human therapeutic dose, respectively

Contraception

• Females: Use effective contraception during treatment and for 6 months after final dose
• Males: May damage spermatozoa; advise males with female sexual partners of reproductive potential to use effective contraception during treatment and for 3 months after final dose

Infertility

• Males: Based on animal findings, may impair fertility

Lactation

Data are not available regarding drug in human milk or effects on breastfed infant or milk production

Because of potential harm; advise women not to breastfeed during treatment and for 9 days after final dose

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.

Mechanism of Action

Semi-synthetic vinca alkaloid; inhibits mitosis at metaphase by depolymerizing microtubules; specific for S ans M phases; may also inhibit nucleic acid and protein synthesis by blocking glutamic acid use

Pharmacokinetics

Half-Life: 28-44 hr

Peak Plasma: 234-1160 ng/mL

Plasma clearance: 0.97-1.26 L/hr/kg

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%)

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
• 0.9% NaCl
• 0.45% NaCl
• D5W 0.45% NaCl
• Lactated Ringer (LR)
• Ringer’s

Y-site (partial list)

• Buprenorphine, cisplatin, cyclophosphamide, diphenhydramine, gemcitabine, fluconazole, granisetron, hydromorphone, imipenem-cilastatin, lorazepam, meperidine, morphine, ondansetron, KCl, vancomycin, zidovudine

IV Preparation

Prepare in infusion bag only

Dilute to 0.5-2 mg/mL in 0.9% NaCl, 0.45% NaCl, D5W, D5/0.45% NaCl, LR or Ringer's

IV Administration

Vesicant

For IVPB use only; fatal if given intrathecally

Always properly position IV needle or catheter before any infusion

Infuse over 6-10 min through sidearm of free-flowing IV closest to IV bag

Flush with 75-125 mL of one of the IV compatible 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

Unopened vials: Refrigerate; protected from light

Diluted solution: Store for 24 hr under normal light at 5-30ºC