(vi NOR el been)
Treatment of non-small cell lung cancer (NSCLC)
Pretreatment granulocyte counts <1000/mm3
Vinorelbine tartrate injection should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
Not for intrathecal use:This product is for intravenous (IV) use only. Intrathecal administration of other vinca alkaloids has resulted in death. Syringes containing this product should be labeled "Warning " for IV use only. Fatal if given intrathecally. "
Bone marrow suppression:Severe granulocytopenia resulting in increased susceptibility to infection may occur. Granulocyte counts should be greater than or equal to 1000 cells/mm3 prior to the administration of vinorelbine tartrate. The dosage should be adjusted according to complete blood counts with differentials obtained on the day of treatment.
Extravasation:It is extremely important that the IVs needle or catheter be properly positioned before vinorelbine tartrate is injected. Administration of vinorelbine tartrate may result in extravasation causing local tissue necrosis or thrombophlebitis.
Non-small cell lung cancer (NSCLC): IV:
Single-agent therapy: 30 mg/m2 every 7 days until disease progression or unacceptable toxicity
Combination therapy: 25-30 mg/m2 every 7 days (in combination with cisplatin)
Off-label dosing: 25 mg/m2 days 1 and 8 every 21 days (in combination with cisplatin and cetuximab) for up to 6 cycles (Pirker, 2009) or 25-30 mg/m2 days 1, 8, and 15 every 28 days (in combination with gemcitabine) for 6 cycles or until disease progression or unacceptable toxicity (Herbst, 2002; Greco, 2007)
Breast cancer, metastatic (off-label use): IV: 25 mg/m2 every 7 days (as a single agent) until disease progression or unacceptable toxicity (Zelek, 2001) or 30 mg/m2 every 7 days (as a single agent); after 13 weeks, may administer every 14 days for patient convenience, continue until disease progression or unacceptable toxicity (Vogel, 1999) or 25 mg/m2 every 7 days (in combination with trastuzumab) until disease progression or unacceptable toxicity (Burstein, 2001; Burstein 2007) or 30 or 35 mg/m2 days 1 and 8 every 21 days (in combination with trastuzumab) until disease progression or unacceptable toxicity (Andersson, 2011)
Cervical cancer (off-label use): IV: 30 mg/m2 days 1 and 8 of a of a 21-day treatment cycle (Muggia, 2004; Muggia, 2005)
Hodgkin lymphoma, relapsed or refractory (off-label use): IV:
GVD regimen: 15 mg/m2 (post-transplant patients) or 20 mg/m2 (transplant-na ¯ve patients) on days 1 and 8 of a 21-day cycle (in combination with gemcitabine and doxorubicin liposomal) for 2 to 6 cycles (Bartlett, 2007 )
IGEV regimen: 20 mg/m2 on day 1 of a 21-day cycle (in combination with ifosfamide, mesna, gemcitabine, and prednisolone) for 4 cycles (Santoro, 2007)
Malignant pleural mesothelioma (off-label use): IV: 30 mg/m2 (maximum dose: 60 mg) every 7 days per 6-week treatment cycle, continue until disease progression (Stebbing, 2009) or 30 mg/m2 (maximum dose: 60 mg) every 7 days for 6 weeks, off 2 weeks, then repeat cycle (Muers, 2008)
Ovarian cancer, relapsed (off-label use): IV: 25 mg/m2 every 7 days (Bajetta, 1996) or 30 mg/m2 days 1 and 8 of a 21-day treatment cycle (Rothenberg, 2004) until disease progression or unacceptable toxicity
Salivary gland cancer, recurrent (off-label use): IV: 25 mg/m2 on days 1 and 8 of a 21-day cycle (in combination with cisplatin) for a minimum of 3 cycles and for up to 6 cycles (Airoldi, 2001) or 30 mg/m2 every 7 days (monotherapy) for a minimum of 9 weeks and for up to 6 cycles (Airoldi, 2001)
Small cell lung cancer, refractory (off-label use): IV: 25 or 30 mg/m2 every 7 days until disease progression or unacceptable toxicity (Furuse, 1996; Jessem, 1993)
Soft tissue sarcoma, advanced (off-label use): IV: 25 mg/m2 days 1 and 8 of a 21-day treatment cycle (in combination with gemcitabine) until disease progression or unacceptable toxicity (Dileo, 2007)
Refer to adult dosing.
Renal insufficiency: No dosage adjustment necessary.
Hemodialysis: Initial: IV: Reduce dose to 20 mg/m2/week; administer either after dialysis (on dialysis days) or on nondialysis days (Janus, 2010)
Note: In patients with concurrent hematologic toxicity and hepatic impairment, administer the lower of the doses determined from the adjustment recommendations.
Administer 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 ≤2 mg/dL: Administer 100% of dose
Serum bilirubin 2.1-3 mg/dL: Administer 50% of dose (Ecklund, 2005; Floyd, 2006; Superfin, 2006)
Serum bilirubin >3 mg/dL: Administer 25% of dose (Ecklund, 2005; Floyd, 2006; Superfin, 2006)
Patients (breast cancer) with extensive liver metastases (>75% of liver volume): Administer 50% of dose (Ecklund, 2005; Superfin, 2006)
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Dilute in D5W or NS to a final concentration of 1.5-3 mg/mL (for syringe) or D5W, NS, 1/2NS, D51/2NS, LR, or Ringers to a final concentration of 0.5 to 2 mg/mL (for IV bag). Vinorelbine should NOT be prepared during the preparation of any intrathecal medications.
For IV use only; FATAL IF GIVEN INTRATHECALLY. Administer as a direct intravenous push or rapid bolus, over 6-10 minutes (up to 30 minutes). Longer infusions may increase the risk of pain and phlebitis. Intravenous doses should be followed by at least 75-125 mL of saline or D5W to reduce the incidence of phlebitis and inflammation.
Vesicant; ensure proper needle or catheter position prior to administration. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry warm compresses for 20 minutes 4 times a day for 1-2 days; elevate extremity (Perez Fidalgo, 2012). Remaining portion of the vinorelbine dose should be infused through a separate vein.
Hyaluronidase: If needle/cannula still in place, administer 1-6 mL hyaluronidase (150 units/mL) into the existing IV line; the usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug (Perez Fidalgo, 2012; Schulmeister, 2011). If needle/cannula was removed, inject 1-6 mL (150 units/mL) subcutaneously in a clockwise manner using 1mL for each 1 mL of drug extravasated (Schulmeister, 2011) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) subcutaneously into the extravasation site (Polovich, 2009).
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Store intact vials refrigerated at 2 °C to 8 °C (36 °F to 46 °F); do not freeze. Protect from light. Intact vials are stable at room temperature of 25 °C (77 °F) for up to 72 hours. Solutions diluted for infusion in polypropylene syringes (D5W or NS) or polyvinyl chloride bags (D5W, NS, 1/2NS, D51/2NS, LR, or Ringers) are stable for 24 hours at 5 °C to 30 °C (41 °F to 86 °F). After preparation, keep vinorelbine in a location away from the separate storage location recommended for intrathecal medications.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Navelbine: 10 mg/mL (1 mL); 50 mg/5 mL (5 mL)
Generic: 10 mg/mL (1 mL); 50 mg/5 mL (5 mL)
Solution, Intravenous [preservative free]:
Generic: 10 mg/mL (1 mL); 50 mg/5 mL (5 mL)
Stable in D51/2NS, D5W, LR, NS, 1/2NS.
Y-site administration: Incompatible with acyclovir, allopurinol, aminophylline, amphotericin B, amphotericin B cholesteryl sulfate complex, ampicillin, cefazolin, cefotetan, ceftriaxone, cefuroxime, fluorouracil, furosemide, ganciclovir, methylprednisolone sodium succinate, mitomycin, piperacillin, sodium bicarbonate, thiotepa, trimethoprim/sulfamethoxazole.
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Ceritinib: May increase the serum concentration of CYP3A4 Substrates. Management: Use of ceritinib with a narrow therapeutic index CYP3A substrate (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) should be avoided when possible. Monitor therapy
CISplatin: May enhance the adverse/toxic effect of Vinorelbine. Specifically, the combination may be associated with a higher risk of granulocytopenia. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Vinorelbine. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gefitinib: May enhance the neutropenic effect of Vinorelbine. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Macrolide Antibiotics: May increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Macrolides may also increase the distribution of Vinca Alkaloids into certain cells and/or tissues. Management: Consider an alternative to using a macrolide antibiotic when possible in order to avoid the potential for increased vinca alkaloid toxicity. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
MitoMYcin (Systemic): Antineoplastic Agents (Vinca Alkaloids) may enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
PACLitaxel (Conventional): May enhance the neurotoxic effect of Vinorelbine. Monitor therapy
PACLitaxel (Protein Bound): May enhance the neurotoxic effect of Vinorelbine. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Posaconazole: May enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Posaconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Management: Consider vinca alkaloid dose adjustment. Specific dose adjustment guidelines are not currently available. Monitor response to vinca alkaloid therapy, including development of vinca alkaloid toxicities (e.g., gastrointestinal toxicity, neurotoxicity). Consider therapy modification
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Voriconazole: May enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Voriconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Consider therapy modification
CBC with differential and platelet count (prior to each dose, and after treatment), hepatic function tests; monitor for new-onset pulmonary symptoms (or worsening from baseline); monitor for neuropathy (new or worsening symptoms; monitor infusion site; monitor for signs symptoms of constipation/ileus
Note: Reported with single-agent therapy.
>10%:
Central nervous system: Fatigue (27%)
Dermatologic: Alopecia (12% to 30%)
Gastrointestinal: Nausea (31% to 44%; grade 3: 1% to 2%), constipation (35%; grade 3: 3%), vomiting (20% to 31%; grade 3: 1% to 2%), diarrhea (12% to 17%)
Hematologic: Leukopenia (83% to 92%; grade 4: 6% to 15%), granulocytopenia (90%; grade 4: 36%; nadir: 7-10 days; recovery 14-21 days), neutropenia (85%; grade 4: 28%), anemia (83%; grades 3/4: 9%)
Hepatic: AST increased (67%; grade 3: 5%; grade 4: 1%), total bilirubin increased (5% to 13%; grade 3: 4%; grade 4: 3%)
Local: Injection site reaction (22% to 28%; includes erythema, vein discoloration), injection site pain (16%)
Neuromuscular & skeletal: Weakness (36%), peripheral neuropathy (25%; grade 3: 1%; grade 4: <1%)
Renal: Creatinine increased (13%)
1% to 10%:
Cardiovascular: Chest pain (5%)
Dermatologic: Rash (<5%)
Gastrointestinal: Paralytic ileus (1%)
Hematologic: Neutropenic fever/sepsis (8%; grade 4: 4%), thrombocytopenia (3% to 5%; grades 3/4: 1%)
Local: Phlebitis (7% to 10%)
Neuromuscular & skeletal: Loss of deep tendon reflexes (<5%), myalgia (<5%), arthralgia (<5%), jaw pain (<5%)
Otic: Ototoxicity ( ≤1%)
Respiratory: Dyspnea (7%)
<1% (Limited to important or life-threatening): Abdominal pain, allergic reactions, anaphylaxis, angioedema, back pain, DVT, dysphagia, esophagitis, flushing, gait instability, headache, hemolytic uremic syndrome, hemorrhagic cystitis, hyper-/hypotension, hyponatremia, intestinal necrosis, intestinal obstruction, intestinal perforation, interstitial pulmonary changes, local rash, local urticaria, MI (rare), mucositis, muscle weakness, myocardial ischemia, pancreatitis, paralytic ileus, pneumonia, pruritus, pulmonary edema, pulmonary embolus, radiation recall (dermatitis, esophagitis), skin blistering, syndrome of inappropriate ADH secretion, tachycardia, thromboembolic events, thrombotic thrombocytopenic purpura, tumor pain, urticaria, vasodilation
Concerns related to adverse effects:
- Bone marrow suppression: [U.S. Boxed Warning]: Severe granulocytopenia may occur with treatment (may lead to infection); granulocyte counts should be ≥1000 cells/mm3 prior to treatment initiation; dosage adjustment may be required based on blood counts (monitor blood counts prior to each dose). Granulocytopenia is a dose-limiting toxicity; nadir is generally 7-10 days after administration and recovery occurs within the following 7-14 days. Monitor closely for infections and/or fever in patients with severe granulocytopenia. Use with extreme caution in patients with compromised marrow reserve due to prior chemotherapy or radiation therapy.
- Extravasation: [U.S. Boxed Warning]: Vesicant; ensure proper catheter or needle position prior to (and during) infusion. Avoid extravasation. Extravasation may cause local tissue necrosis and/or thrombophlebitis.
- Gastrointestinal toxicity: May cause severe constipation (grade 3-4), paralytic ileus, intestinal obstruction, necrosis, and/or perforation; some events were fatal. Oral vinorelbine (not available in the U.S.) is associated with a moderate antiemetic potential; antiemetics are recommended to prevent nausea/vomiting (Dupuis, 2011; Roila, 2010); IV vinorelbine has a minimal emetic potential (Dupuis, 2011; Roila, 2010).
- Neuropathy: May cause new-onset or worsening of pre-existing neuropathy; use with caution in patients with neuropathy. Monitor for new or worsening sign/symptoms of neuropathy. Dosage adjustment required.
- Pulmonary toxicity: Fatal cases of interstitial pulmonary changes and ARDS have been reported with single-agent therapy (mean onset of symptoms: 1 week). Promptly evaluate changes in baseline pulmonary symptoms or any new-onset pulmonary symptoms (eg, dyspnea, cough, hypoxia). Acute shortness of breath and severe bronchospasm have been reported with vinca alkaloids, usually when used in combination with mitomycin.
Disease-related concerns:
- Hepatic impairment: Vinorelbine elimination is predominantly hepatic. While there is no evidence that toxicity is enhanced in patients with elevated transaminases, use with caution in patients with severe hepatic injury or impairment; dosage modification required for elevated total bilirubin.
- Radiation therapy: May have radiosensitizing effects with prior or concurrent radiation therapy; radiation recall reactions may occur in patients who have received prior radiation therapy.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]); avoid eye contamination (exposure may cause severe irritation).
Other warnings/precautions:
- Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
- NOT for intrathecal use: [U.S. Boxed Warning]: For IV use only; intrathecal administration of other vinca alkaloids has resulted in death. If dispensed in a syringe, should be labeled "for intravenous use only - fatal if given intrathecally. Vinorelbine should NOT be prepared during the preparation of any intrathecal medications. After preparation, keep vinorelbine in a location away from the separate storage location recommended for intrathecal medications.
D
Animal reproduction studies have demonstrated embryotoxicity, fetotoxicity, decreased fetal weight, and delayed ossification. May cause fetal harm if administered during pregnancy. Women of childbearing potential should avoid becoming pregnant during vinorelbine treatment.
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. Vinorelbine may also interfere with nucleic acid and protein synthesis by blocking glutamic acid utilization.
Vd: binds extensively to human platelets and lymphocytes (80% to 91%)
Children and Adolescents 2 to 17 years: 21.1 ± 12.2 L/kg (Johansen 2006)
Adults: 25 to 40 L/kg
Extensively hepatic, via CYP3A4, to two metabolites, deacetylvinorelbine (active) and vinorelbine N-oxide
Feces (46%); urine (18%, 10% to 12% as unchanged drug)
Triphasic:
Children and Adolescents 2 to 17 years: Terminal: 16.5 ± 9.7 hours (Johansen 2006)
Adults: Terminal: 28 to 44 hours
80% to 91%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience constipation, diarrhea, or hair loss. Have patient report immediately to prescriber signs of infection, injection site pain or irritation, angina, shortness of breath, burning or numbness feeling, severe abdominal pain, loss of strength and energy, bruising, bleeding, severe nausea, vomiting, difficulty breathing, slow breathing, shallow breathing, or severe constipation, rectal pain, or rectal bleeding (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.