Navelbine

Vinca Alkaloids and Analogs

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
IV Doses: Minimal
Administer prn antiemetics as necessary.
Extravasation Risk
Vesicant
Administer drug through a central venous line.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Vinorelbine is for intravenous (IV) use only; fatalities have been associated with intrathecal administration of vinca alkaloids.[56871] [64256]
The Institute for Safe Medication Practices (ISMP) recommends dispensing vinca alkaloids in a minibag of a compatible solution to prevent accidental intrathecal administration; this best practice is supported by other accrediting and professional organizations.[64256] [64348] [64349] [64350] [64351]
Ensure the IV needle or catheter is properly positioned before administration; monitor the infusion site and immediately discontinue and administer appropriate treatment (e.g., hyaluronidase, application of heat) if extravasation occurs.[56871]
 
Intermittent IV Infusion
In a flexible plastic container (i.e., minibag), dilute the calculated dose/volume of vinorelbine in a compatible IV fluid (e.g., 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, Ringer's Injection, or Lactated Ringer's Injection) to a final concentration between 0.5 and 2 mg/mL.[56871]
ISMP recommends a diluent volume of 25 mL for pediatric patients and 50 mL for adults.[64256]
Storage of admixture (in polyvinyl chloride bags): Store for up to 24 hours under normal light conditions at 5 to 30 degrees C (41 to 86 degrees F).
Administer IV over 6 to 10 minutes into the side port of a free-flowing IV line; flush with at least 75 to 125 mL of a compatible solution.[56871]

neutropenia / Delayed / 29.0-69.0
leukopenia / Delayed / 12.0-32.0
anemia / Delayed / 1.0-9.0
hyperbilirubinemia / Delayed / 5.0-9.0
neurotoxicity / Early / 7.0-8.5
asthenia / Delayed / 5.0-7.0
elevated hepatic enzymes / Delayed / 3.0-6.0
injection site reaction / Rapid / 0-5.0
constipation / Delayed / 2.0-3.0
dyspnea / Early / 2.0-3.0
weakness / Early / 0-3.0
vomiting / Early / 1.0-2.0
nausea / Early / 1.0-2.0
alopecia / Delayed / 1.0-2.0
thrombocytopenia / Delayed / 0-1.0
diarrhea / Early / 0.5-1.0
phlebitis / Rapid / 0-1.0
SIADH / Delayed / 0-1.0
ototoxicity / Delayed / 0-1.0
hemorrhagic cystitis / Delayed / 0-1.0
myocardial infarction / Delayed / 0-0.1
GI perforation / Delayed / Incidence not known
ileus / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
tissue necrosis / Early / Incidence not known
pulmonary embolism / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
pulmonary toxicity / Early / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
pulmonary edema / Early / Incidence not known
pancreatitis / Delayed / Incidence not known

chest pain (unspecified) / Early / 5.0-5.0
bone marrow suppression / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
erythema / Early / Incidence not known
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / Incidence not known
radiation recall reaction / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypertension / Early / Incidence not known
hypotension / Rapid / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
hyponatremia / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known

infection / Delayed / Incidence not known
fever / Early / Incidence not known
abdominal pain / Early / Incidence not known
anorexia / Delayed / Incidence not known
weight loss / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
hyporeflexia / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
rash / Early / Incidence not known
flushing / Rapid / Incidence not known
back pain / Delayed / Incidence not known
headache / Early / Incidence not known

Severe bone marrow suppression including neutropenia, anemia, and thrombocytopenia occurs in patients treated with vinorelbine and can lead to infection, septic shock, hospitalization, and death. Neutropenia is the major dose-limiting toxicity, with the nadir between days 7 and 10, and recovery typically within the following 7 to 14 days. Monitor complete blood counts prior to each dose of vinorelbine; a dose adjustment may be necessary based on day-of-treatment neutrophil counts. Do not administer vinorelbine to patients with neutrophil counts less than 1,000 cells/mm3.

Navelbine

Rx

Semi-synthetic vinca alkaloid; microtubule inhibitor
Used for the treatment of metastatic non-small cell lung cancer
Vesicant; closely monitor for signs and symptoms of extravasation

30 mg/m2 IV over 6 to 10 minutes, once weekly. Coadministration of certain drugs may require special caution; review drug interactions. Treatment with vinorelbine monotherapy improved the median survival time in patients with previously untreated stage IV NSCLC compared with fluorouracil/leucovorin in a multicenter, randomized, open-label clinical trial (30 weeks vs. 22 weeks). Partial objective responses were observed in 11.1% and 3.5% of patients, respectively.

25 mg/m2 IV over 6 to 10 minutes on days 1, 8, 15, and 22, in combination with cisplatin (100 mg/m2 IV on day 1) every 28 days. Coadministration of certain drugs may require special caution; review drug interactions. Treatment with vinorelbine and every-4-week cisplatin significantly improved the overall response rate (19% vs. 8%) and median overall survival (7.8 months vs. 6.2 months) in patients with previously untreated stage IIIb or IV NSCLC compared with cisplatin alone in a randomized, open-label clinical trial.

25 or 30 mg/m2 IV once weekly for up to 16 doses in combination with cisplatin [34316] [34317] has been evaluated in randomized, phase 3 studies. Coadministration of certain drugs may require special caution; review drug interactions. Adjuvant therapy with vinorelbine (30 mg/m2 IV once weekly starting on day 1 for up to 16 doses) plus cisplatin (100 mg/m2 on days 1, 29, 57, and 85) led to significantly improved median overall survival (OS) (65.7 vs. 43.7 months) and disease-free survival (DFS) (36.3 vs. 20.7 months) compared with surgery +/- radiotherapy alone in a multinational, randomized, phase 3 study in 840 patients with completely resected stage IB-IIIA NSCLC. The absolute OS improvement at 2- and 5-years was 4.7% and 8.4%, respectively. In the adjuvant chemotherapy arm, grade 3 or 4 neutropenia was reported in 85% of patients and there were 7 (2%) treatment-related deaths.[34316] In another randomized, phase 3 study, adjuvant therapy with vinorelbine (25 mg/m2 IV weekly for 16 weeks) plus cisplatin (50 mg/m2 on days 1 and 8 repeated every 4 weeks for 4 cycles) resulted in significantly improved median OS (94 vs. 73 months) and relapse-free survival (not reached vs. 46.7 months) compared with surgery alone in 482 patients with stage IB or II NSCLC. The absolute improvement in 5-year OS was 11% at a median follow-up time of 9.3 years. In a post-hoc analysis, no OS benefit was observed in patients with stage IB disease. Grade 3 and 4 neutropenia was reported in 73% of patients and there were 2 (0.8%) treatment-related deaths.[34317] [45478]

25 mg/m2 IV on days 1 and 8 in combination with cisplatin (80 mg/m2 IV on day 1) every 21 days, and cetuximab (400 mg/m2 IV the first week with subsequent weekly infusions of 250 mg/m2 IV). Cisplatin and vinorelbine are given up to 6 cycles. Weekly cetuximab should continue until unacceptable toxicity or disease progression. Coadministration of certain drugs may require special caution; review drug interactions. In a phase 3 trial of 1,125 patients with advanced EGFR-detectable non-small cell lung cancer, the addition of cetuximab to the doublet cisplatin and vinorelbine significantly improved the primary endpoint overall survival (11.3 months vs. 10.1 months). Response rate (36% vs. 29%) and time to treatment failure (4.2 months vs. 3.7 months) were also significantly greater in the cetuximab arm. Patients who received cetuximab had a significantly higher incidence of febrile neutropenia (22% vs. 15%).[35499] Multiple previous trials of EGFR-targeted tyrosine kinase inhibitors in combination with chemotherapy in the front-line treatment of patients with non-small cell lung cancer have generally shown no additional survival benefit with the addition of the tyrosine kinase inhibitor.[30549] [30550] [34184] [34185] [43302]

30 mg/m2 IV over 6 to 10 minutes once weekly in combination with cisplatin (120 mg/m2 IV on days 1 and 29, then every 6 weeks). Coadministration of certain drugs may require special caution; review drug interactions. Treatment with vinorelbine plus every-6-week cisplatin significantly improved the response rate (28% vs. 14%) and median overall survival (9.2 months vs. 7.2 months) in patients with previously untreated stage III or IV NSCLC compared with vinorelbine monotherapy in a randomized, open-label clinical trial.

30 mg/m2 or 35 mg/m2 IV on days 1 and 8, every 3 weeks, in combination with trastuzumab (8 mg/kg IV over 90 minutes on day 1 (of cycle 1 only), followed 3 weeks later by 6 mg/kg IV over 30 minutes repeated every 3 weeks). Alternatively, administer vinorelbine 25 mg/m2 IV once weekly, in combination with trastuzumab (4 mg/kg IV over 90 minutes on week 1 (of first cycle only), then 2 mg/kg IV over 30 minutes once weekly). In a phase 3 clinical trial, treatment with vinorelbine (30 mg/m2 or 35 mg/m2) plus trastuzumab did not significantly improve time to progression (15.3 months vs. 12.4 months) or overall survival (38.8 months vs. 35.7 months) compared with docetaxel plus trastuzumab in patients with previously untreated locally advanced or metastatic breast cancer. In a phase 2 clinical trial, the overall response rate was 58% and median time to treatment failure was 5.6 months in patients treated with vinorelbine (25 mg/m2 IV weekly) plus trastuzumab. This regimen was also shown to be similar to taxane-trastuzumab combinations in another phase 2 clinical trial.

30 mg/m2 IV over 6 to 10 minutes weekly, repeated every 21 days; alternatively, 30 mg/m2 IV over 6 to 10 minutes on days 1 and 8, every 21 days. The addition of gemcitabine to vinorelbine significantly improved median progression-free survival (PFS) compared with vinorelbine alone (6 months vs. 4 months) in a multicenter, randomized, phase 3 study in patients with locally recurrent and metastatic breast cancer who had previously received anthracyclines and taxanes; however, neither the median overall survival (OS) nor the objective response rate (ORR) were significantly different. In another multicenter, randomized, phase 3 study of patients with taxane-refractory, locally advanced or metastatic breast cancer, treatment with an investigator choice regimen consisting of either single-agent vinorelbine or mitomycin C plus vinblastine did not significantly improve median PFS (2.5 months vs. 2.9 months), median OS (9 months vs. 10.4 months), or ORR (12% vs. 10%) compared with pegylated liposomal doxorubicin. The median time to disease progression (105 vs. 84 days) and median OS (283 vs. 284 days) were not significantly different with single-agent docetaxel or vinorelbine in yet another randomized study in patients with metastatic breast cancer in patients who had previously received doxorubicin, epirubicin, or mitoxantrone.

25 mg/m2 IV weekly plus trastuzumab 4 mg/kg IV once followed by trastuzumab 2 mg/kg IV weekly and everolimus 5 mg PO once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided with everolimus or everolimus dosage adjustments may be necessary; review drug interactions. Everolimus plus vinorelbine and trastuzumab significantly improved progression-free survival compared with placebo plus vinorelbine and trastuzumab in patients with HER2-positive, trastuzumab-resistant advanced breast cancer in patients who had received prior taxane therapy; objective response rate and overall survival were not significantly improved.

30 mg/m2 once weekly or on days 1 and 8, every 21 days. In a phase 2 study of 79 patients with recurrent epithelial ovarian cancer (EOC) who had previously received both platinum and taxane therapy, 30 mg/m2 IV push (into the tubing of a free-flowing IV infusion) on days 1 and 8 repeated every 21 days resulted in a 6-month overall survival (OS) rate of 65%, a median OS time of 10.1 months, and an ORR of 3%. The median OS times were 8 months in 52 patients with chemotherapy-resistant disease and 16 months in 27 patients with chemotherapy-sensitive disease. Grade 3 and 4 toxicity included granulocytopenia (56%) and leukopenia (47%).[45386] In a multicenter, phase 2 study in 38 women with persistent or recurrent EOC who had previously received a platinum-based chemotherapy regimen, 30 mg/m2 IV over 20 minutes repeated once weekly until disease progression or unacceptable toxicity led to a time to treatment failure of 12 weeks, median OS time of 60 weeks, and an ORR of 29%. Grade 3 and 4 granulocytopenia was reported in 63% of patients.[45387]

30 mg/m2 given as an IV infusion once weekly until disease progression or unacceptable toxicity resulted in a median time to progression of 12 weeks, a median overall survival time of 32 weeks, and an overall response rate of 14% in a phase 2 study in 63 eligible patients with advanced recurrent and/or metastatic squamous cell carcinoma of the head and neck. Grade 3 and 4 toxicity included leukopenia (51%) and neutropenia (53%); additionally, infection occurred in 46% of patients and was the cause of early death in 2 patients.

20 mg/m2 IV plus methotrexate (30 mg/m2 or 50 mg IV) both given weekly has been studied. Vinorelbine plus methotrexate 50 mg IV resulted in a complete or substantial partial remission rate of 60% in 17 patients with symptomatic fibromatosis or desmoid tumor not amenable to curative surgical resection in a small study. Some patients had previously received treatment with vinblastine plus methotrexate but did not tolerate therapy due to neurotoxicity. In this study, neurotoxicity was reported in 16% of patients. In a retrospective analysis of 94 patients up to 21 years of age with aggressive fibromatosis, an objective response was achieved in 11 of 19 patients (58%) who received vinorelbine or vinblastine in combination with methotrexate (30 mg/m2 IV weekly).

In a retrospective analysis of 94 pediatric patients (age range, 1 month to 21 years) with aggressive fibromatosis, an objective response was achieved in 11 of 19 patients (58%) who received vinorelbine 20 mg/m2 given as an IV bolus weekly or vinblastine (in combination with methotrexate (30 mg/m2 IV weekly).

20 mg/m2 IV over 6 to 10 minutes as a component of the GVD regimen and as a component of the IGEV regimen have been studied. Vinorelbine in combination with gemcitabine (1,000 mg/m2 IV over 30 minutes), and pegylated liposomal doxorubicin (15 mg/m2 IV over 30 to 60 minutes) on days 1 and 8 repeated every 21 days (GVD regimen) for 2 to 6 cycles (or until disease progression or unacceptable toxicity) led to an overall response rate (ORR) of 70% (complete response (CR) rate, 19%) in a phase 1/2 study in 91 patients. Reduced doses of chemotherapy (gemcitabine 800 mg/m2, vinorelbine 15 mg/m2, and pegylated liposomal doxorubicin 10 mg/m2) were administered to 37 of 40 patients who had previously received a transplant. The 4-year event-free survival and overall survival (OS) rates were 52% and 70%, respectively, in transplant-naive patients and 10% and 34%, respectively, in patients who had previously received a transplant. Thirty-nine transplant-naive patients received an autologous transplant following GVD therapy. One treatment-related death was reported in this study. Treatment with vinorelbine on day 1 plus ifosfamide (2,000 mg/m2 IV over 2 hours on days 1 to 4 with 2,000 mL of hydration and mesna 2,600 mg/m2 IV on days 1 to 4), gemcitabine (800 mg/m2 IV on days 1 and 4), and prednisolone (100 mg on days 1 to 4) repeated every 3 weeks (IGEV regimen) for up to 4 cycles led to an ORR of 81.3% (complete remission (CR) rate, 53.8%) in a multicenter study in 91 patients; additionally, 3-year freedom from progression and OS rates were 52.98% and 70.03%, respectively. Sixty-four patients in complete or partial remission received single or tandem high-dose chemotherapy with peripheral blood stem cell support after 4 IGEV cycles.

†Indicates off-label use

Total bilirubin 2 mg/dL or less: No dosage adjustment required.
Total bilirubin 2.1 to 3 mg/dL: Reduce the dose of vinorelbine to 50% of the original dose.
Total bilirubin greater than 3 mg/dL: Reduce the dose of vinorelbine to 25% of the original dose.
Note: For patients with concurrent hematologic toxicity and hepatic impairment/hepatotoxicity, administer the lower of the recommended dose adjustments based on the corresponding starting dose of vinorelbine.
Patients with diffuse liver metastases (more than 75% of liver volume replaced by tumor): Consider reducing the dose of vinorelbine to 50% of the original dose.

No dosage adjustment necessary.

Adagrasib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with adagrasib is necessary. Vinorelbine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Amiodarone: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amiodarone is necessary. Vinorelbine is a CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor.
Amlodipine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Atorvastatin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Benazepril: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Celecoxib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Olmesartan: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Valsartan: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Consider if an alternative to clarithromycin is appropriate in patients who will undergo vinorelbine therapy. Monitor for vinorelbine-related side effects, including neurotoxicity and neutropenia, if these drugs must be used together. Increased concentrations of vinorelbine are likely. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vinorelbine is a CYP3A4 and P-gp substrate. Reports of interactions, including serious toxicity, between clarithromycin and vinca alkaloids have been noted.
Asciminib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with asciminib is necessary. Vinorelbine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Atazanavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with atazanavir is necessary. Vinorelbine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Atazanavir; Cobicistat: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with atazanavir is necessary. Vinorelbine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinorelbine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Avacopan: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with avacopan is necessary. Vinorelbine is a CYP3A substrate and avacopan is a weak CYP3A inhibitor.
Belumosudil: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with belumosudil is necessary. Vinorelbine is a CYP3A substrate and belumosudil is a weak CYP3A inhibitor.
Berotralstat: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with berotralstat is necessary. Vinorelbine is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor.
Bicalutamide: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with bicalutamide is necessary. Vinorelbine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Ceritinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ceritinib is necessary. Vinorelbine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chloramphenicol: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with chloramphenicol is necessary. Vinorelbine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cimetidine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cimetidine is necessary. Vinorelbine is a CYP3A4 substrate and cimetidine is a weak CYP3A4 inhibitor.
Ciprofloxacin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ciprofloxacin is necessary. Vinorelbine is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor.
Clarithromycin: (Moderate) Consider if an alternative to clarithromycin is appropriate in patients who will undergo vinorelbine therapy. Monitor for vinorelbine-related side effects, including neurotoxicity and neutropenia, if these drugs must be used together. Increased concentrations of vinorelbine are likely. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vinorelbine is a CYP3A4 and P-gp substrate. Reports of interactions, including serious toxicity, between clarithromycin and vinca alkaloids have been noted.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Cobicistat: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinorelbine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Conivaptan: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with conivaptan is necessary. Vinorelbine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with crizotinib is necessary. Vinorelbine is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cyclosporine is necessary. Vinorelbine is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor.
Dalfopristin; Quinupristin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with dalfopristin; quinupristin is necessary. Vinorelbine is a CYP3A4 substrate and dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Danazol: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with danazol is necessary. Vinorelbine is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor.
Darunavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with darunavir is necessary. Vinorelbine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinorelbine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with darunavir is necessary. Vinorelbine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinorelbine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with darunavir is necessary. Vinorelbine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Delavirdine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with delavirdine is necessary. Vinorelbine is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor.
Diltiazem: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with diltiazem is necessary. Vinorelbine is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor.
Dronedarone: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with dronedarone is necessary. Vinorelbine is a CYP3A4 substrate and dronedarone is a moderate CYP3A4 inhibitor.
Duvelisib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with duvelisib is necessary. Vinorelbine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Elbasvir; Grazoprevir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with grazoprevir is necessary. Vinorelbine is a CYP3A4 substrate and grazoprevir is a weak CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinorelbine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinorelbine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Erythromycin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with erythromycin is necessary. Vinorelbine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Everolimus: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with everolimus is necessary. Vinorelbine is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fedratinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fedratinib is necessary. Vinorelbine is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fluconazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fluconazole is necessary. Vinorelbine is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor.
Fluoxetine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fluoxetine is necessary. Vinorelbine is a CYP3A4 substrate. Fluoxetine is a weak CYP3A4 inhibitor, but its active metabolite, norfluoxetine, is a moderate inhibitor of CYP3A4.
Fluvoxamine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fluvoxamine is necessary. Vinorelbine is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor.
Fosamprenavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fosamprenavir is necessary. Vinorelbine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fostamatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fostamatinib is necessary. Vinorelbine is a CYP3A4 substrate and fostamatinib is a weak CYP3A4 inhibitor.
Gadobenate Dimeglumine: (Moderate) Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as vinca alkaloids, may result in prolonged systemic exposure of the coadministered drug. Caution is advised if these drugs are used together.
Ganciclovir: (Moderate) Use ganciclovir and vinca alkaloids together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Grapefruit juice: (Moderate) Instruct patients that consuming grapefruit or grapefruit juice may result in earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy. Vinorelbine is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
Idelalisib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with idelalisib is necessary. Vinorelbine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Imatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with imatinib is necessary. Vinorelbine is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Indinavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with indinavir is necessary. Vinorelbine is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor.
Isavuconazonium: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with isavuconazonium is necessary. Vinorelbine is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
Isoniazid, INH: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with isoniazid is necessary. Vinorelbine is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with isoniazid is necessary. Vinorelbine is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor.
Isoniazid, INH; Rifampin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with isoniazid is necessary. Vinorelbine is a CYP3A4 substrate and isoniazid is a weak CYP3A4 inhibitor.
Istradefylline: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with istradefylline 40 mg daily is necessary. Vinorelbine is a CYP3A4 and P-gp substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor and P-gp inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Major) Avoid the use of vinorelbine during and for 2 weeks after discontinuation of itraconazole due to the risk of an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy. Vinorelbine is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Concomitant administration of another vinca alkaloid with itraconazole has resulted in an increased incidence of neurotoxicity.
Ketoconazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ketoconazole is necessary. Vinorelbine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Consider if an alternative to clarithromycin is appropriate in patients who will undergo vinorelbine therapy. Monitor for vinorelbine-related side effects, including neurotoxicity and neutropenia, if these drugs must be used together. Increased concentrations of vinorelbine are likely. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vinorelbine is a CYP3A4 and P-gp substrate. Reports of interactions, including serious toxicity, between clarithromycin and vinca alkaloids have been noted.
Lapatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with lapatinib is necessary. Vinorelbine is a CYP3A4 substrate and lapatinib is a weak CYP3A4 inhibitor.
Larotrectinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with larotrectinib is necessary. Vinorelbine is a CYP3A4 substrate and larotrectinib is a weak CYP3A4 inhibitor.
Lefamulin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with oral lefamulin is necessary. Vinorelbine is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Lenacapavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with lenacapavir is necessary. Vinorelbine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with letermovir is necessary; in patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Vinorelbine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Levoketoconazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ketoconazole is necessary. Vinorelbine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor.
Live Vaccines: (Contraindicated) Do not administer live vaccines to vinorelbine recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vinorelbine. Before initiation of vinorelbine therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vinorelbine recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Lonafarnib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with lonafarnib is necessary. Vinorelbine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ritonavir is necessary. Vinorelbine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Maribavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with maribavir is necessary. Vinorelbine is a CYP3A substrate and maribavir is a weak CYP3A inhibitor.
Mifepristone: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with chronic mifepristone therapy is necessary. Vinorelbine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Mitomycin: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Nefazodone: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with nefazodone is necessary. Vinorelbine is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor.
Nelfinavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with nelfinavir is necessary. Vinorelbine is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with netupitant is necessary. Vinorelbine is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor.
Nicardipine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with nicardipine is necessary. Vinorelbine is a CYP3A4 substrate and nicardipine is a weak CYP3A4 inhibitor.
Nilotinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with nilotinib is necessary. Vinorelbine is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ritonavir is necessary. Vinorelbine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Olanzapine; Fluoxetine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fluoxetine is necessary. Vinorelbine is a CYP3A4 substrate. Fluoxetine is a weak CYP3A4 inhibitor, but its active metabolite, norfluoxetine, is a moderate inhibitor of CYP3A4.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Pacritinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with pacritinib is necessary. Vinorelbine is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
Palbociclib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with palbociclib is necessary. Vinorelbine is a CYP3A4 substrate and palbociclib is a weak CYP3A4 inhibitor.
Pazopanib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with pazopanib is necessary. Vinorelbine is a CYP3A4 substrate and pazopanib is a weak CYP3A4 inhibitor.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Perindopril; Amlodipine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Pirtobrutinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with pirtobrutinib is necessary. Vinorelbine is a CYP3A substrate and pirtobrutinib is a weak CYP3A inhibitor.
Posaconazole: (Major) Avoid coadministration of posaconazole with vinorelbine if possible due to increased plasma concentrations of vinorelbine. If concomitant use is unavoidable and alternative antifungal options are not available, frequently monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy. Vinorelbine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant administration of azole antifungals, including posaconazole, with another vinca alkaloid has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Quinine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with quinine is necessary. Vinorelbine is a CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor.
Ranolazine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ranolazine is necessary. Vinorelbine is a CYP3A4 substrate and ranolazine is a weak CYP3A4 inhibitor.
Ribociclib: (Moderate) Monitor for increased severity or earlier onset of vinorelbine-related adverse reactions if coadministration with ribociclib is necessary. Vinorelbine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for increased severity or earlier onset of vinorelbine-related adverse reactions if coadministration with ribociclib is necessary. Vinorelbine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ritlecitinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ritlecitinib is necessary. Vinorelbine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ritonavir is necessary. Vinorelbine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Rucaparib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with rucaparib is necessary. Vinorelbine is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor.
Saquinavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with saquinavir is necessary. Vinorelbine is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with selpercatinib is necessary. Vinorelbine is a CYP3A4 substrate and selpercatinib is a weak CYP3A4 inhibitor.
Spironolactone: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with spironolactone is necessary. Vinorelbine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with spironolactone is necessary. Vinorelbine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Streptogramins: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with dalfopristin; quinupristin is necessary. Vinorelbine is a CYP3A4 substrate and dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Telmisartan; Amlodipine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with amlodipine is necessary. Vinorelbine is a CYP3A4 substrate and amlodipine is a weak CYP3A4 inhibitor.
Ticagrelor: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ticagrelor is necessary. Vinorelbine is a CYP3A4 substrate and ticagrelor is a weak CYP3A4 inhibitor.
Tipranavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with tipranavir is necessary. Vinorelbine is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor.
Trandolapril; Verapamil: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with verapamil is necessary. Vinorelbine is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor.
Trofinetide: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with trofinetide is necessary. Vinorelbine is a CYP3A substrate and trofinetide is a weak CYP3A inhibitor.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Tucatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with tucatinib is necessary. Vinorelbine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valganciclovir: (Moderate) Use valganciclovir and vinca alkaloids together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Verapamil: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with verapamil is necessary. Vinorelbine is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor.
Viloxazine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with viloxazine is necessary. Vinorelbine is a CYP3A4 substrate and viloxazine is a weak CYP3A4 inhibitor.
Vonoprazan; Amoxicillin: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with vonoprazan is necessary. Vinorelbine is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Consider if an alternative to clarithromycin is appropriate in patients who will undergo vinorelbine therapy. Monitor for vinorelbine-related side effects, including neurotoxicity and neutropenia, if these drugs must be used together. Increased concentrations of vinorelbine are likely. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vinorelbine is a CYP3A4 and P-gp substrate. Reports of interactions, including serious toxicity, between clarithromycin and vinca alkaloids have been noted. (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with vonoprazan is necessary. Vinorelbine is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Major) Avoid coadministration of voriconazole with vinorelbine if possible due to increased plasma concentrations of vinorelbine. If concomitant use is unavoidable and alternative antifungal options are not available, frequently monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy. Vinorelbine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Concomitant administration of azole antifungals with another vinca alkaloid has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Voxelotor: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with voxelotor is necessary. Vinorelbine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zafirlukast: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with zafirlukast is necessary. Vinorelbine is a CYP3A4 substrate and zafirlukast is a weak CYP3A4 inhibitor.

Navelbine/Vinorelbine/Vinorelbine Tartrate Intravenous Inj Sol: 1mL, 10mg

30 mg/m2 IV.

30 mg/m2 IV.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Vinorelbine is a semi-synthetic vinca alkaloid. It acts as a microtubule inhibitor, causing cellular instability and preventing mitosis at metaphase. Microtubules are responsible for intracellular transport, maintenance of cell shape, polarity, cell signaling, and mitosis. During mitosis, microtubules form the mitotic spindle that transports daughter chromosomes to separate poles of the dividing cell. Vinorelbine may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent calcium-transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis. Vinorelbine inhibited mitotic microtubule formation in intact mouse embryo tectal plates at a concentration of 2 micromolar, inducing a blockade of cells at metaphase; however, it produced depolymerization of axonal microtubules at a concentration of 40 micromolar. This suggests a modest selectivity of vinorelbine for mitotic microtubules.

Vinorelbine is administered intravenously. It demonstrates high binding to human platelets and lymphocytes. The free fraction was approximately 0.11 in human plasma over a concentration range of 234 ng/mL to 1,169 ng/mL. The binding to plasma constituents in cancer patients ranged from 79.6% to 91.2%. The steady-state volume of distribution (Vss) of vinorelbine ranged from 25.4 L/kg to 40.1 L/kg. Vinorelbine plasma concentrations decay in a triphasic manner. The terminal phase half-life averaged 27.7 to 43.6 hours and the mean plasma clearance ranged from 0.97 to 1.26 L/hour/kg. Vinorelbine undergoes substantial hepatic elimination to 2 metabolites: vinorelbine N-oxide and deacetylvinorelbine. Deacetylvinorelbine is the primary metabolite in humans and has antitumor activity similar to vinorelbine; however, therapeutic doses of vinorelbine (30 mg/m2) yield very small, if any, quantifiable levels of either metabolite in blood or urine. After IV administration, approximately 46% of a radioactive dose was recovered in the feces and 18% in the urine. In a different study, 10.9% (+/- 0.7%) of a single IV dose was excreted as parent drug in the urine.[56871]
 
Affected cytochrome P450 (CYP) isoenzymes and drug transporters: CYP3A and P-glycoprotein (P-gp)
Vinorelbine is a CYP3A and a P-gp substrate.[59581] [59600]

Pregnancy should be avoided by females of reproductive potential during vinorelbine treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant women, vinorelbine can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving vinorelbine should be apprised of the potential hazard to the fetus. Administration of a single dose of vinorelbine in a mouse embryo-fetal development study at a dose approximating 0.33 times the recommended human dose based on BSA was both embryotoxic and fetotoxic. Vinorelbine was also embryotoxic and fetotoxic to pregnant rabbits when administered every 6 days during organogenesis at approximately 0.18 times or more the recommended human dose based on BSA. At doses that did not cause maternal toxicity in either species, vinorelbine administration caused reduced fetal weight and delayed ossification.

Due to the potential for serious adverse reactions in nursing infants from vinorelbine, advise women to discontinue breast-feeding during treatment and for 9 days after the final dose. It is not known whether vinorelbine is present in human milk, although many drugs are excreted in human milk.