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Vinorelbine

Medically reviewed by Drugs.com. Last updated on May 17, 2020.

Pronunciation

(vi NOR el been)

Index Terms

  • Dihydroxydeoxynorvinkaleukoblastine
  • Vinorelbine Tartrate
  • Vinorelbine, inj

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 10 mg/mL (1 mL [DSC]); 50 mg/5 mL (5 mL [DSC])

Solution, Intravenous [preservative free]:

Navelbine: 10 mg/mL (1 mL); 50 mg/5 mL (5 mL)

Generic: 10 mg/mL (1 mL); 50 mg/5 mL (5 mL)

Brand Names: U.S.

  • Navelbine

Pharmacologic Category

  • Antineoplastic Agent, Antimicrotubular
  • Antineoplastic Agent, Vinca Alkaloid

Pharmacology

Vinorelbine is a 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.

Distribution

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

Metabolism

Extensively hepatic, via CYP3A4, to two metabolites, deacetylvinorelbine (active) and vinorelbine N-oxide

Excretion

Feces (~46%); urine (~18%, 10% to 12% as unchanged drug)

Half-Life Elimination

Triphasic:

Children and Adolescents 2 to 17 years: Terminal: 16.5 ± 9.7 hours (Johansen 2006)

Adults: Terminal: ~28 to 44 hours

Protein Binding

80% to 91%

Use: Labeled Indications

Non-small cell lung cancer: Treatment (first-line; in combination with cisplatin) of locally advanced or metastatic non-small cell lung cancer (NSCLC); single-agent treatment of metastatic NSCLC.

Off Label Uses

Breast cancer, metastatic

Data from two multicenter randomized trials evaluating the use of vinorelbine in patients with HER-2 positive advanced or metastatic breast cancer supports the use of vinorelbine in the treatment of this condition [Andersson 2011], [ Burstein 2007]. Data from two phase 2 studies also demonstrated activity of vinorelbine in the treatment of metastatic breast cancer unresponsive to anthracyclines, taxanes, and vinorelbine (in combination with trastuzumab) for the treatment of metastatic breast cancer without prior chemotherapy [Zelek 2001], [Burstein 2001].

Cervical cancer, persistent or recurrent

Data from a phase 2 study evaluating vinorelbine in patients with advanced or recurrent squamous cell carcinoma of the cervix refractory to standard local therapy (which could include primary chemoradiation) supports the use of vinorelbine in this condition [Muggia 2004]. Data from a phase 2 study evaluating vinorelbine in patients with recurrent or persistent nonsquamous cell carcinoma of the cervix who received prior chemotherapy also supports the use of vinorelbine for this condition [Muggia 2005].

Hodgkin lymphoma, relapsed or refractory

Data from a phase 1/2 trial evaluating vinorelbine (in combination with gemcitabine and doxorubicin) in patients with relapsed or refractory Hodgkin lymphoma supports the use of vinorelbine for the treatment of this condition [Bartlett 2007]. Data from a study evaluating vinorelbine (in combination with ifosfamide and gemcitabine) in patients with relapsed or refractory Hodgkin lymphoma supports the use of vinorelbine for the treatment of this condition [Santoro 2007].

Malignant pleural mesothelioma

Data from a phase 2 open-label study evaluating vinorelbine in patients with relapsed malignant pleural mesothelioma suggests that vinorelbine may be beneficial for the treatment of this condition [Stebbing 2009]. Data from a multicenter randomized controlled trial in patients with recently diagnosed malignant pleural mesothelioma demonstrated that adding vinorelbine to active symptom control offers no significant benefit; however, the authors determined, based on exploratory analyses, that the role of vinorelbine deserves further investigation [Muers 2008].

Ovarian cancer, relapsed

Data from two phase 2 studies evaluating vinorelbine in patients with recurrent or resistant epithelial ovarian cancer (after treatment with platinum and/or taxane) support the use of vinorelbine for the treatment of relapsed ovarian cancer [Bajetta 1996], [Rothenberg 2004].

Salivary gland cancer, recurrent

Data from a small, phase 2, randomized study evaluating vinorelbine (in combination with cisplatin versus vinorelbine monotherapy) in patients with recurrent salivary gland cancer supports the use of vinorelbine (in combination with cisplatin) for this condition [Airoldi 2001].

Small cell lung cancer, refractory

Data from two phase 2 studies evaluating vinorelbine in patients with refractory small cell lung cancer supports the use of vinorelbine in the treatment of this condition [Furuse 1996], [Jassem 1993].

Soft tissue sarcoma, advanced

Data from a phase 2, randomized study evaluating vinorelbine (in combination with gemcitabine) in patients with unresectable or metastatic soft-tissue sarcomas supports the use of vinorelbine in the treatment of this condition [Dileo 2007].

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

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 change dosing interval to 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 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-naive 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)

Non-small cell lung cancer (NSCLC): IV:

Metastatic (single-agent therapy): 30 mg/m2 once a week

Locally advanced or metastatic (in combination with cisplatin): 25 mg/m2 on days 1, 8, 15, and 22 of a 28-day cycle or 30 mg/m2 once a week

Advanced NSCLC (off-label dosing): 25 to 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 (Greco 2007; Herbst 2002)

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)

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; Jassem 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)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precautions to verify dosing parameters during calculations. Protocol-specific details concerning dosing, frequency, and combination regimens should be consulted.

Hodgkin lymphoma, refractory or recurrent: Limited data available; dosing regimens and combinations variable: Children ≥10 years and Adolescents:

GV regimen: IV: 25 mg/m2 on days 1 and 8 of a 21-day cycle in combination with gemcitabine (Cole 2009).

GVD regimen: IV: 20 mg/m2 on day 1 and 8 of a 21-day cycle in combination with gemcitabine and pegylated liposomal doxorubicin (Jaffray 2015).

IVB regimen: IV: 25 mg/m2 on days 1 and 5 of a 21-day cycle in combination with ifosfamide and bortezomib (Horton 2015).

Leukemias (acute ALL, AML), refractory or recurrent: Limited data available:

TVTC regimen:

Infants: IV: 0.67 mg/kg once weekly on days 0, 7, 14 of a 14-day cycle in combination with topotecan, clofarabine, and thiotepa (Steinherz 2010).

Children and Adolescents: IV: 20 mg/m2 once weekly on days 0, 7, and 14 of a 14-day cycle in combination with topotecan, clofarabine, and thiotepa (Shukla 2014; Steinherz 2010).

BDMV regimen: Infants ≥9 months, Children, and Adolescents: IV: 25 mg/m2 on days 3, 10, and 17 in combination with bortezomib, dexamethasone, and mitoxantrone (Yeo 2016).

Solid tumors, refractory or recurrent: Limited data available: Children and Adolescents:

Monotherapy: IV: 30 mg/m2 once weekly for weeks 1 to 6 of an 8-week cycle for 10 courses; may reduce dosage to 27 mg/m2 for Grade 3 or 4 hematologic toxicity in patients who demonstrate objective response or who have had treatment delay beyond 63 days (week 9) from the previous course (Kuttesch 2009).

Combination therapy: IV: 25 mg/m2 on days 1, 8, and 15 of each 28-day cycle in combination with cyclophosphamide (Casanova 2004; Minard-Colin 2012).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.

Adult: Note: In patients with concurrent hematologic toxicity and hepatic impairment, administer the lower of the doses determined from the adjustment recommendations.

Neutrophil counts should be ≥1,000 cells/mm3 prior to the administration of vinorelbine. Adjustments in the dosage of vinorelbine should be based on neutrophil counts obtained on the day of treatment as follows:

Neutrophils ≥1,500 cells/mm3 on day of treatment: Administer 100% of starting dose.

Neutrophils 1,000 to 1,499 cells/mm3 on day of treatment: Administer 50% of starting dose.

Neutrophils <1,000 cells/mm3 on day of treatment: Do not administer. Repeat neutrophil count in 1 week; if 3 consecutive doses are held because neutrophil count is <1,000 cells/mm3, discontinue vinorelbine.

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

Neutrophils ≥1,500 cells/mm3: Administer 75% of starting dose.

Neutrophils 1,000 to 1,499 cells/mm3 on day of treatment: Administer 37.5% of starting dose.

Neutrophils <1,000 cells/mm3 on day of treatment: Do not administer. Repeat neutrophil count in 1 week.

Neurotoxicity (peripheral neuropathy or autonomic neuropathy causing constipation) ≥ grade 2: Discontinue treatment.

Severe adverse events: Reduce dose or discontinue treatment.

Dosing: Adjustment for Toxicity

Non-small cell lung cancer:

Note: In patients with concurrent hematologic toxicity and hepatic impairment, administer the lower of the doses determined from the adjustment recommendations.

Dosage adjustment in hematological toxicity (based on neutrophil counts):

Neutrophils ≥1,500/mm3 on day of treatment: Administer 100% of vinorelbine starting dose.

Neutrophils 1,000 to 1,499/mm3 on day of treatment: Administer 50% of vinorelbine starting dose.

Neutrophils <1,000/mm3 on day of treatment: Do not administer vinorelbine. Repeat neutrophil count in 1 week. If 3 consecutive doses are held because neutrophil count is <1,000/mm3, discontinue vinorelbine.

Adjustment: For patients who, during treatment, have experienced fever or sepsis while neutrophils were <1,500/mm3 or had 2 consecutive weekly doses held due to neutropenia, subsequent vinorelbine doses should be:

Neutrophils ≥1,500/mm3: Administer 75% of vinorelbine starting dose.

Neutrophils 1,000 to 1,499/mm3: Administer 37.5% of vinorelbine starting dose.

Neutrophils <1,000/mm3: Do not administer vinorelbine; repeat neutrophil count in 1 week.

Dosage adjustment for neurotoxicity: Neurotoxicity (peripheral neuropathy or autonomic neuropathy causing constipation) ≥ grade 2: Discontinue vinorelbine treatment.

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (ASCO [Griggs 2012]).

Reconstitution

Dilute in D5W, NS, 1/2NS, D51/2NS, LR, or Ringer's to a final concentration (in the IV bag) of 0.5 to 2 mg/mL. The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinca alkaloids in a minibag (NOT a syringe) (ISMP 2018). Vinorelbine should NOT be prepared during the preparation of any intrathecal medications (Jacobson 2009).

Administration

IV: For IV use only; fatal if given by other routes. Administer over 6 to 10 minutes (the manufacturer recommends infusing into the side port of a free-flowing IV line); follow the infusion with at least 75 to 125 mL of a compatible solution 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 to 2 days; elevate extremity (Pérez Fidalgo 2012). Remaining portion of the vinorelbine dose should be infused through a separate vein.

Hyaluronidase: If needle/cannula still in place, administer 1 to 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 (Pérez Fidalgo 2012; Schulmeister 2011). If needle/cannula was removed, inject 1 to 6 mL (150 units/mL) subcutaneously in a clockwise manner using 1 mL 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).

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Intact (unopened) vials are stable at 25°C (77°F) for up to 72 hours. Solutions diluted for infusion in polyvinyl chloride bags (D5W, NS, 1/2NS, D51/2NS, LR, or Ringer's) are stable for up to 24 hours at 5°C to 30°C (41°F to 86°F) under normal room light. After preparation, keep vinorelbine in a location away from the separate storage location recommended for intrathecal medications (Jacobson 2009).

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

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

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. 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

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inhibitors). Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Vinorelbine. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

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

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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 (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Gefitinib: May enhance the neutropenic effect of Vinorelbine. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inhibitors). Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. 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 (High risk with Inhibitors). Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

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. Consider therapy modification

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or 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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Neurotoxicity (44%), peripheral neuropathy (20%; grades 3/4: 1%)

Dermatologic: Alopecia (12% to 30%)

Gastrointestinal: Nausea (≤34%), vomiting (≤31%), constipation (29%), diarrhea (12% to 13%)

Hematologic & oncologic: Neutropenia (80% to 85%; grades 3/4: 29% to 69%), leukopenia (81% to 83%; grades 3/4: 12% to 32%), anemia (77%; grades 3/4: 1% to 9%)

Hepatic: Increased serum aspartate aminotransferase (54%)

Local: Injection site reaction (22% to 38%; includes erythema at injection site, vein discoloration), pain at injection site (13%)

Neuromuscular & skeletal: Asthenia (27%)

Renal: Increased serum creatinine (13%)

1% to 10%:

Cardiovascular: Localized phlebitis (10%), chest pain (5%)

Central nervous system: Neuropathy (grades 3/4: 1%)

Hematologic & oncologic: Febrile neutropenia (≤8%), thrombocytopenia (3% to 4%; grades 3/4: 1%)

Hepatic: Increased serum bilirubin (9%)

Infection: Sepsis (≤8%)

Otic: Ototoxicity (1%)

Respiratory: Dyspnea (3%)

Frequency not defined:

Gastrointestinal: Intestinal necrosis, intestinal obstruction, intestinal perforation, paralytic ileus

Hematologic & oncologic: Bone marrow depression

Hepatic: Hepatotoxicity

Respiratory: Interstitial pulmonary disease, pulmonary toxicity (including acute respiratory distress syndrome, interstitial pneumonitis, severe acute bronchospasm)

<1%, postmarketing, and/or case reports: Abdominal pain, abnormal gait, anaphylaxis, angioedema, arthralgia, auditory impairment, back pain, decreased deep tendon reflex, deep vein thrombosis, dermatitis, dysphagia, electrolyte disorder, esophagitis, exfoliation of skin, flushing, headache, hemorrhagic cystitis, hypertension, hyponatremia, hypotension, jaw pain, localized rash, mucositis, myalgia, myasthenia, myocardial infarction, palmar-plantar erythrodysesthesia, pancreatitis, pneumonia, pruritus, pulmonary edema, pulmonary embolism, radiation recall phenomenon, SIADH, skin blister, skin rash, tachycardia, tumor pain, urticaria, urticaria at injection site, vasodilation, vestibular disturbance

ALERT: U.S. Boxed Warning

Bone marrow suppression:

Severe myelosuppression resulting in serious infection, septic shock, hospitalization, and death can occur. Decrease the dose or withhold vinorelbine in accord with recommended dose modifications.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Severe myelosuppression resulting in serious infection, septic shock, hospitalization, and death may occur. May require treatment interruption, dose reduction, and/or discontinuation. Neutropenia, thrombocytopenia, and anemia may occur with vinorelbine (either as a single agent or in combination with other chemotherapy); neutropenia is the major dose-limiting toxicity (grade 3 or 4 neutropenia has commonly occurred). Neutropenia has resulted in hospitalization (for fever) and/or sepsis. The neutrophil nadir occurs between 7 to 10 days after administration, and recovery occurs within the following 7 to 14 days. Monitor complete blood counts prior to each dose. Adjust dose based on blood counts obtained on the day of treatment. Do not administer if ANC <1,000/mm3.

• Extravasation: 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: Severe and fatal paralytic ileus, constipation, intestinal obstruction, necrosis, and perforation may occur with vinorelbine. Begin a prophylactic bowel regimen (including adequate dietary fiber intake, hydration, and routine stool softeners) to minimize potential constipation, bowel obstruction and/or paralytic ileus. Oral vinorelbine (not available in the US) is associated with a moderate or high antiemetic potential; antiemetics are recommended to prevent nausea/vomiting (POGO [Dupuis 2011]; ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); IV vinorelbine has a minimal emetic potential.

• Hepatitis B virus screening: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

• Hepatotoxicity: Drug-induced liver injury (transaminase and bilirubin elevations) may occur in patients receiving vinorelbine (either as a single-agent or in combination with other chemotherapy). Monitor liver function prior to treatment initiation and periodically during treatment. Dose reductions are recommended in patients who develop total bilirubin elevations >2 times ULN. Vinorelbine elimination is predominantly hepatic; use with caution in patients with hepatic impairment; dose reductions are recommended.

• Neuropathy: Sensory and motor neuropathies may occur in patients receiving vinorelbine; may be severe. Monitor for new or worsening sign/symptoms of neuropathy, including paresthesia, hyperesthesia, hyporeflexia, and muscle weakness. Discontinue vinorelbine for ≥ grade 2 neuropathy.

• Pulmonary toxicity: Pulmonary toxicity, including severe acute bronchospasm, interstitial pneumonitis, and/or acute respiratory distress syndrome (ARDS) may occur with vinorelbine; fatalities due to interstitial pneumonitis and ARDS have occurred. The mean time to onset of interstitial pneumonitis and ARDS was 1 week (range: 3 to 8 days). Interrupt vinorelbine treatment in patients who develop unexplained dyspnea or with any evidence of pulmonary toxicity. Permanently discontinue vinorelbine with confirmed interstitial pneumonitis or ARDS.

Other warnings/precautions:

• For IV use only: Vinorelbine is for IV administration only. Administration of other vinca alkaloids by other routes has been fatal. The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinca alkaloids in a minibag (NOT a syringe) (ISMP 2018). 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 (Jacobson 2009).

Monitoring Parameters

CBC with differential and platelet count (prior to each dose, and after treatment), hepatic function tests. Hepatitis B virus screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). Verify pregnancy status prior to treatment initiation (in females of reproductive potential). Monitor for new-onset pulmonary symptoms (or worsening from baseline); monitor for neuropathy (new or worsening symptoms); monitor for signs/symptoms of constipation/ileus; monitor infusion site.

Reproductive Considerations

Females of reproductive potential should use effective contraception during vinorelbine treatment and for 6 months after the final vinorelbine dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months following the last vinorelbine dose.

Vinorelbine may damage spermatozoa and may cause decreased fertility in male patients.

Pregnancy Considerations

Based on the mechanism and on findings in animal reproduction studies, vinorelbine may cause fetal harm if administered to a pregnant female.

Patient Education

What is this drug used for?

• It is used to treat lung cancer.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Lack of appetite

• Weight loss

• Muscle pain

• Joint pain

• Diarrhea

• Hair loss

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Severe injection site redness, burning, swelling, pain or irritation

• Muscle weakness

• Burning or numbness feeling

• Severe loss of strength and energy

• Chest pain

• Severe constipation

• Rectal pain

• Rectal bleeding

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.