vinorelbine

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
vine-oh-rel-been


Trade Name(s)

  • Navelbine

Ther. Class.

antineoplastics

Pharm. Class.

vinca alkaloids

Indications

Inoperable non-small-cell lung cancer (as monotherapy or in combination with cisplatin).

Action

Binds to a protein (tubulin) of cellular microtubules, where it interferes with microtubule assembly. Cell replication is stopped as a result (cell cycle–specific for M phase).

Therapeutic Effect(s):

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Highly bound to platelets and lymphocytes.

Metabolism and Excretion: Mostly metabolized by the liver. At least one metabolite is active. Large amounts eliminated in feces; 11% excreted unchanged by the kidneys.

Half-life: 28–44 hr.

TIME/ACTION PROFILE (effect on WBCs)

ROUTEONSETPEAKDURATION
IVunknown7–10 days7–15 days

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Active infection;
  • ↓ bone marrow reserve;
  • OB:   Pregnancy;
  • Lactation:  Lactation.

Use Cautiously in:

  • Hepatic impairment (dose ↓ recommended if total bilirubin >2 m g/dL);
  • Debilitated patients (↑ risk of hyponatremia);
  • Granulocytopenia (temporarily discontinue or reduce dose);
  • Rep:   Women of reproductive potential;
  • Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: chest pain

Derm: alopecia, rash

F and E: hyponatremia

GI: constipation, nausea, ↑ in liver enzymes, abdominal pain, anorexia, diarrhea, vomiting

Hemat: anemia, neutropenia, thrombocytopenia

Local: irritation at iv site, phlebitis

MS: arthralgia, back pain, jaw pain, myalgia

Neuro: fatigue, neurotoxicity

Resp: shortness of breath

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • ↑ bone marrow depression with other  antineoplastics  or  radiation therapy.
  • Concurrent use with  cisplatin  ↑ risk and severity of bone marrow depression.
  • Concurrent use with  mitomycin  or  chest radiation  ↑ risk of pulmonary reactions.

Route/Dosage

IV (Adults): 30 mg/m2  once weekly.

Hepatic Impairment 
IV (Adults):   Total bilirubin 2.1–3 mg/dL:  15 mg/m2  once weekly;  total bilirubin ≥3 mg/dL:  7.5 mg/m2  once weekly.

Availability (generic available)

Solution for injection: 10 mg/mL

Assessment

  • Monitor BP, pulse, and respiratory rate during therapy. Note significant changes. Acute shortness of breath and severe bronchospasm may occur infrequently shortly after administration. Treatment with corticosteroids, bronchodilators, and supplemental oxygen may be required, especially in patients with a history of pulmonary disease.
  • Assess frequently for signs of infection (sore throat, temperature, cough, mental status changes), especially when nadir of granulocytopenia is expected.
  • Monitor neurologic status. Assess for paresthesia (numbness, tingling, pain), loss of deep tendon reflexes (Achilles reflex is usually first involved), weakness (wrist drop or footdrop, gait disturbances), cranial nerve palsies (jaw pain, hoarseness, ptosis, visual changes), autonomic dysfunction (constipation, ileus, difficulty voiding, orthostatic hypotension, impaired sweating), and CNS dysfunction (decreased level of consciousness, agitation, hallucinations). These symptoms may persist for mo. The incidence of neurotoxicity associated with vinorelbine is less than that of other vinca alkaloids.
  • Monitor intake and output and daily weight for significant discrepancies.
  • Assess nutritional status. Mild to moderate nausea is common. An antiemetic may be used to minimize nausea and vomiting.
  • Monitor for symptoms of gout (increased uric acid, joint pain, edema). Encourage patient to drink at least 2 L of fluid/day. Allopurinol and alkalinization of urine may decrease uric acid levels.

Lab Test Considerations:

Monitor CBC prior to each dose and routinely during therapy. The nadir of granulocytopenia usually occurs 7–10 days after vinorelbine administration and recovery usually follows within 7–15 days. If granulocyte count is <1500/mm3 , dose reduction or temporary interruption of vinorelbine may be warranted. If repeated episodes of fever and/or sepsis occur during granulocytopenia, future dose of vinorelbine should be modified. May also cause mild to moderate anemia. Thrombocytopenia rarely occurs.

  • Monitor liver function studies (AST, ALT, LDH, bilirubin) and renal function studies (BUN, creatinine) prior to and periodically during therapy. May cause ↑ uric acid; monitor periodically during therapy.

Implementation

  • High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, dose calculations, and infusion pump settings.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.

    • Assess infusion site frequently for redness, irritation, or inflammation. Vinorelbine is a vesicant. If extravasation occurs, infusion must be stopped and restarted elsewhere to avoid damage to SUBQ tissue. Treatment of extravasation includes application of warm compresses applied over the area immediately for 30–60 min, then alternating on/off every 15 min for 1 day to increase systemic absorption of the drug. Hyaluronidase 150 units diluted in 1–2 mL of 0.9% NaCl, 1 mL for each mL extravasated, should be injected through existing IV cannula or SUBQ if the needle has been removed to enhance absorption and dispersion of the extravasated drug.

IV Administration

  • IV Push:   Dilution:  Dilute vinorelbine with 0.9% NaCl or D5W. Concentration: 1.5–3 mg/mL.
  • Rate: 

    Infuse over 6–10 min into Y-site closest to bag of a free-flowing IV or into a central line.

    • Flush vein with at least 75–125 mL of 0.9% NaCl or D5W administered over 10 min or more following administration of vinorelbine.
  • Intermittent Infusion:   Dilution:  Dilute vinorelbine with 0.9% NaCl, D5W, 0.45% NaCl, D5/0.45% NaCl, Ringer's or lactated Ringer's injection. Solution should be colorless to pale yellow. Do not administer solutions that are discolored or contain particulate matter. Diluted solution is stable for 24 hr at room temperature. Concentration:  0.5–2 mg/mL.
  • Rate: 

    Infuse over 6–10 min (up to 30 min) into Y-site closest to bag of a free-flowing IV or into a central line.

    • Flush vein with at least 75–125 mL of 0.9% NaCl or D5W administered over 10 min or more following administration of vinorelbine.
  • Y-Site Compatibility:
    • amikacin
    • aztreonam
    • bleomycin
    • MORE...
      • bumetanide
      • buprenorphine
      • butorphanol
      • calcium gluconate
      • carboplatin
      • carmustine
      • cefotaxime
      • ceftazidime
      • chlorpromazine
      • cisplatin
      • clindamycin
      • cyclophosphamide
      • cytarabine
      • dacarbazine
      • dactinomycin
      • daunorubicin hydrochloride
      • dexamethasone
      • diphenhydramine
      • doxorubicin hydrochloride
      • doxorubicin liposomal
      • doxycycline
      • droperidol
      • enalaprilat
      • etoposide
      • famotidine
      • filgrastim
      • floxuridine
      • fluconazole
      • fludarabine
      • gemcitabine
      • gentamicin
      • granisetron
      • haloperidol
      • hydrocortisone
      • hydromorphone
      • idarubicin
      • ifosfamide
      • imipenem/cilastatin
      • lorazepam
      • mannitol
      • melphalan
      • meperidine
      • mesna
      • methotrexate
      • metoclopramide
      • metronidazole
      • mitoxantrone
      • morphine
      • nalbuphine
      • ondansetron
      • oxaliplatin
      • potassium chloride
      • prochlorperazine
      • promethazine
      • tobramycin
      • vancomycin
      • vinblastine
      • vincristine
      • zidovudine
  • Y-Site Incompatibility:
    • acyclovir
    • allopurinol
    • aminophylline
    • MORE...
      • amphotericin B deoxycholate
      • ampicillin
      • cefazolin
      • ceftriaxone
      • cefuroxime
      • fluorouracil
      • furosemide
      • ganciclovir
      • lansoprazole
      • methylprednisolone
      • mitomycin
      • sodium bicarbonate
      • thiotepa
      • trimethoprim/sulfamethoxazole

Patient/Family Teaching

  • Instruct patient to report symptoms of neurotoxicity (paresthesia, pain, difficulty walking, persistent constipation).
  • Inform patient that increased fluid intake, dietary fiber, and exercise may minimize constipation. Stool softeners or laxatives may be necessary. Patient should be advised to report severe constipation or abdominal discomfort, as this may be a sign of ileus, which may occur as a consequence of neuropathy.
  • Advise patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; or mouth sores occur.
  • Caution patient to avoid crowds and persons with known infections.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 2 mo after last dose of vinorelbine and to avoid breastfeeding during and for 9 days after last dose.
  • Discuss with patient the possibility of hair loss and explore coping strategies.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

Decrease in the size or spread of malignancy without detrimental side effects.

vinorelbineis the Emergency Central Word of the day!