Vinorelbine is a semi-synthetic vinca alkaloid derived from the Catharanthus roseus or Madagascar periwinkle plant. 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 is more potent and less neurotoxic than vinblastine and vincristine. Vinorelbine is indicated for the treatment of non-small cell lung cancer (NSCLC) as monotherapy and in combination with cisplatin. The primary dose-limiting toxicity is neutropenia. Monitor complete blood counts prior to each dose; an adjustment to the dose of vinorelbine may be necessary for neutropenia. Vinorelbine is also a vesicant; monitor closely for signs of extravasation.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
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.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Vinorelbine is for intravenous (IV) use only; fatalities have been associated with intrathecal administration of vinca alkaloids.
-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.
-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.
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.
-ISMP recommends a diluent volume of 25 mL for pediatric patients and 50 mL for adults.
-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.
Bone marrow suppression commonly occurs in patients treated with vinorelbine. Neutropenia is the major dose-limiting toxicity, with the neutrophil nadir between days 7 and 10, and recovery within the following 7 to 14 days. In clinical trials, neutropenia was reported in 80% to 90% (grade 4, 29% to 69%), leukopenia in 81% to 92% (grade 4, 12% to 32), anemia in 77% to 83% (grade 3 or 4, 1% to 9%), and thrombocytopenia in 3% to 5% (grade 3 or 4, 1% or less) of patients receiving vincristine monotherapy in pooled results from 4 clinical trials. Overall, the incidence of neutropenia (89% to 95%; grade 3 or 4, 78% to 82%), leukopenia (88% to 94%; grade 3 or 4, 57% to 58%), anemia (89%; grade 3 or 4, 24%), and thrombocytopenia (15% to 29%; grade 3 or 4, 4% to 5%) were similar in a clinical trial of patients with previously untreated NSCLC receiving vinorelbine plus cisplatin, although the grade of grade 3 or 4 hematologic adverse reactions was much higher. Hospitalizations due to neutropenic complications occurred in 8% to 9% of patients treated with vinorelbine monotherapy. Febrile neutropenia was reported in 11% of NSCLC patients who received vinorelbine plus cisplatin in a randomized clinical trial. Monitor complete blood counts; an interruption of therapy, dose adjustment, or discontinuation of therapy may be necessary.
Fever was among the most frequently reported adverse reactions leading to discontinuation of vinorelbine monotherapy in pooled results from 3 clinical trials. In one clinical trial of patients with previously untreated NSCLC, fever without infection (20% vs. 4%; grade 3 or 4, 2% vs. 0%), infection (11% vs. less than 1%; less than 6% vs. less than 1%), and respiratory tract infection (10% vs. 3%; grade 3 or 4, less than 5% vs. 3%) were more common in patients treated with vinorelbine plus cisplatin compared with cisplatin alone. Pneumonia has been reported in patients treated with vinorelbine in postmarketing experience.
Nausea (34% to 44%; grade 3 or 4, 1% to 2%), vomiting (15% to 20%; grade 3 or 4, 1% to 2%), and diarrhea (12% to 17%; grade 3 or 4, 0.5% to 1%) have been reported in patients treated with vinorelbine monotherapy in pooled results from 3 clinical trials; in one randomized clinical trial, 31% of patients receiving vinorelbine monotherapy reported a grouped term of nausea/vomiting (grade 3 or 4, 2%). When vinorelbine was administered in combination with cisplatin, the incidence of nausea (58%; grade 3 or 4, 14%) and vomiting (60%; grade 3 or 4, 13%) was increased compared to vinorelbine monotherapy; however, the addition of vinorelbine to cisplatin did not increase the incidence of nausea/vomiting compared with cisplatin monotherapy; the grouped term of nausea/vomiting was reported in 74% of patients treated with vinorelbine plus cisplatin in a randomized clinical trial. The incidence of diarrhea with vinorelbine plus cisplatin (17% to 25%; grade 3 or 4, less than 3%) was similar to patients who received vinorelbine monotherapy. Abdominal pain was additionally reported in postmarketing experience with vinorelbine.
Mild (grade 1 or 2) anorexia or decreased appetite was reported in 46% of patients treated with vinorelbine plus cisplatin compared with 37% of those who received cisplatin monotherapy in a randomized clinical trial; dysgeusia was reported in 17% versus 15% of patients, respectively. In this trial, 34% of patients receiving combination therapy reported weight loss compared with 21% of patients receiving cisplatin monotherapy (grade 3 or 4, 1% vs. less than 1%). Dysphagia occurred in postmarketing experience with vinorelbine.
Severe and fatal paralytic ileus, constipation, GI obstruction, necrosis, and GI perforation can occur with vinorelbine treatment. Patients should be on a prophylactic bowel regimen prior to receiving vinorelbine. Constipation was reported in 29% to 35% of patients receiving vinorelbine monotherapy or in combination with cisplatin in clinical trials (grade 3 or 4, 2% to 3%). Nerve toxicity including both neuropathy and constipation was reported in 44% of patients receiving vinorelbine monotherapy or in combination with cisplatin in clinical trials (grade 3 or 4, 7% to 8.5%). Discontinue therapy for grade 2 or higher autonomic neuropathy causing constipation.
Peripheral neuropathy including paresthesias and hyperesthesia was reported in 20% to 25% of patients receiving vinorelbine monotherapy in pooled results from 3 clinical trials (grade 3 or 4, less than 2%). Hyporeflexia was also a common manifestation of vinorelbine-associated neurotoxicity; loss of deep tendon reflexes has been reported in postmarketing experience with vinorelbine. Peripheral numbness (11% vs. 7%; grade 3 or 4, less than 2%) and paresthesias (17% vs. 10%; grade 3 or 4, less than 1%) occurred slightly more often in patients with NSCLC treated with vinorelbine plus cisplatin compared with cisplatin alone in a randomized clinical trial. Neurotoxicity, including peripheral neuropathy and constipation, was reported in 44% of patients receiving vinorelbine monotherapy or in combination with cisplatin in clinical trials (grade 3 or 4, 7% to 8.5%).
Anaphylactic/anaphylactoid reactions, angioedema, and urticaria have been reported in postmarketing surveillance of vinorelbine.
Vinorelbine is a moderate vesicant and should only be administered intravenously. If extravasation of vinca alkaloids occurs, an injection site reaction caused by direct cellular damage may be expected to cause painful ulceration, local numbness, and slow healing; significant irritation, erythema, tenderness, and intense injection site pain around the port site or IV line may also occur. Erythema may be delayed up to 3 days depending on the administered dose of vinorelbine. This reaction may be followed by blister formation, swelling, and induration and can be complicated by skin sloughing, ulceration, and tissue necrosis. Irritation and burning sensations are commonly reported during administration, which can be prevented by proper dilution, short infusion time, and use of an adequately large vein. In pooled results from 3 clinical trials, an injection site reaction including pain and venous discoloration was reported in 17% to 38% (grade 3 or 4, 5% or less); injection site pain was also reported in 13% to 16% (grade 3 or 4, 1% to 2%) of patients treated with vinorelbine monotherapy.
Chemical phlebitis along the vein proximal to the site of injection was reported in 10% of patients treated with vinorelbine monotherapy in pooled results from 3 clinical trials. Overall, phlebitis was reported in 7% to 10% (grade 3 or 4, 1% or less) of patients who received vinorelbine as monotherapy or in combination with chemotherapy. A grouped term of phlebitis/thrombosis/embolism was reported in 10% (grade 3 or 4, 3%) of patients with previously untreated NSCLC receiving vinorelbine in a randomized clinical trial. Thrombophlebitis may also occur as a result of vinorelbine extravasation. Both pulmonary embolism and deep vein thrombosis have been reported in postmarketing experience with vinorelbine.
Alopecia occurred in 12% to 30% (grade 3 or 4, 2% or less) of patients treated with vinorelbine monotherapy in pooled results from 4 clinical trials; with vinorelbine administered in combination with cisplatin, the incidence of alopecia was 34% to 51% (grade 3 or 4, 7.5% or less). Rash, pruritus, dermatitis, palmar-plantar erythrodysesthesia (hand and foot syndrome), blistering, and sloughing of skin have all been reported in postmarketing experience with vinorelbine.
A radiation recall reaction has been reported with vinorelbine treatment in postmarketing experience.
Chest pain (unspecified) occurred in 5% of patients treated with vinorelbine monotherapy in pooled results from 3 clinical trials; myocardial infarction occurred in less than 0.1% of patients. Sinus tachycardia has been reported with vinorelbine treatment in postmarketing experience.
Hypertension and hypotension have both been reported with vinorelbine treatment in postmarketing experience.
Flushing and peripheral vasodilation were reported with vinorelbine treatment in postmarketing experience.
Syndrome of inappropriate antidiuretic hormone (SIADH) was reported in less than 1% of patients who received vinorelbine monotherapy in pooled results from 3 clinical trials. Electrolyte abnormalities including hyponatremia were reported in postmarketing experience with vinorelbine.
Pulmonary toxicity including severe acute bronchospasm, interstitial pneumonitis, and acute respiratory distress syndrome (ARDS) have occurred in patients receiving vinorelbine; some cases were fatal. The mean time to onset of interstitial pneumonitis and ARDS was 1 week after vinorelbine administration (range, 3 to 8 days). Monitor patients for unexplained dyspnea or other signs or symptoms of pulmonary toxicity; discontinue vinorelbine for confirmed interstitial pneumonitis or ARDS. Dyspnea was reported in 3% to 7% (grade 3 or 4, 2% to 3%) of patients receiving vinorelbine monotherapy in pooled results of 3 clinical trials.
Pulmonary edema was reported with vinorelbine treatment in postmarketing experience.
Ototoxicity was reported in 1% of patients with NSCLC who received vinorelbine monotherapy compared with 10% (grade 3 or 4, 2%) of those treated with vinorelbine plus cisplatin in a randomized clinical trial. Hearing impairment/hearing loss occurred in a similar number of patients with NSCLC treated with vinorelbine plus cisplatin compared with cisplatin alone in another randomized clinical trial (18% vs. 18%; grade 3 or 4, 4% vs. less than 4%). Hearing impairment and vestibular disorders were also reported in postmarketing experience with vinorelbine.
Elevated hepatic enzymes, and specifically increased AST, occurred in 54% to 67% (grade 3 or 4, 3% to 6%) of patients treated with vinorelbine monotherapy in pooled results from 3 clinical trials. Hyperbilirubinemia was reported in 9% to 13% of vinorelbine-treated patients who received monotherapy (grade 3 or 4, 5% to 7%). A vinorelbine dose reduction may be necessary if hyperbilirubinemia occurs.
Hemorrhagic cystitis was reported in less than 1% of cancer patients who received vinorelbine monotherapy in pooled results from 3 clinical trials. Increased serum creatinine occurred in 13% of patients with NCLC who received vinorelbine monotherapy (n = 204) in one clinical trial and in 37% to 46% (grade 3 or 4, 4% or less) of patients receiving vinorelbine plus cisplatin (n = 419) in 2 clinical trials.
A grouped term encompassing fatigue, lethargy, and malaise was reported in 67% of patients with NSCLC treated with vinorelbine plus cisplatin compared with 49% of those who received cisplatin monotherapy in a randomized clinical trial (grade 3 or 4, 12% vs. 8%).
A grouped term including myalgia and arthralgia was reported in 12% of patients with NSCLC treated with vinorelbine plus cisplatin compared with 3% of those receiving cisplatin alone in a randomized clinical trial (grade 3 or 4, less than 1% vs. less than 1%). Myalgia, arthralgia, back pain, jaw pain, and tumor pain were all reported in postmarketing experience with vinorelbine.
Asthenia occurred in 27% to 36% (grade 3 or 4, 5% to 7%) of patients receiving vinorelbine monotherapy in pooled results from 3 clinical trials; asthenia and myasthenia were among the most common reasons for discontinuation of vinorelbine therapy. Weakness was reported slightly more often in patients with NSCLC who received vinorelbine plus cisplatin compared with cisplatin alone in a randomized clinical trial (12% vs. 7%; grade 3 or 4, less than 3% vs. 2%). Muscular weakness and gait disturbance have also been reported in postmarketing experience with vinorelbine.
Pancreatitis was reported with vinorelbine treatment in postmarketing experience.
Mucosal inflammation and esophagitis were reported with vinorelbine treatment in postmarketing experience.
Headache was reported with vinorelbine treatment in postmarketing experience.
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.
Vinorelbine is a moderate vesicant; avoid extravasation of vinorelbine, ocular exposure, and contact with the skin or mucosa. The intravenous needle or catheter must be properly placed prior to vinorelbine administration. Vinorelbine commonly causes venous irritation and burning sensations during administration, which can be prevented by proper dilution, short infusion time, and use of an adequately large vein. If signs or symptoms of extravasation occur, immediately stop administration of vinorelbine and begin recommended management procedures per institutional policies. If vinorelbine contacts the skin or mucosa, immediately wash with soap and water. If ocular exposure occurs, flush the eyes with water immediately and thoroughly.
Fatal neurological effects (e.g., destruction of the central nervous system) have occurred following intrathecal administration of vinca alkaloids; therefore, this route must not be used for vinorelbine. The Institute for Safe Medication Practices (ISMP) recommend 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.
Use vinorelbine with caution in patients with a history of hepatic disease; drug-induced liver injury manifested by increased AST and hyperbilirubinemia can occur during treatment. Assess hepatic function prior to initiation of vinorelbine therapy and periodically during treatment. A dose reduction may be necessary for patients with hyperbilirubinemia.
Use vinorelbine with caution in patients with a history of peripheral neuropathy. Neurotoxicity including sensory and motor neuropathy, in some cases severe, has occurred with vinorelbine treatment. Monitor for new or worsening signs and symptoms of neuropathy, such as paresthesia, hyperesthesia, hyporeflexia, and muscle weakness. Discontinue vinorelbine for grade 2 or higher neuropathy.
Pulmonary toxicity including severe acute bronchospasm, interstitial pneumonitis, and acute respiratory distress syndrome (ARDS) has occurred with vinorelbine treatment. Use vinorelbine with caution in patients with a history of pulmonary disease. The mean time to onset of interstitial pneumonitis and ARDS was 1 week after administration (range, 3 to 8 days). Interrupt vinorelbine therapy for unexplained dyspnea; permanently discontinue therapy for confirmed interstitial pneumonitis or ARDS.
Vinorelbine has been associated with severe and fatal paralytic ileus, constipation, GI obstruction, necrosis, and GI perforation. Use a prophylactic bowel regimen including adequate dietary fiber, hydration, and stool softeners, to mitigate these adverse effects. Discontinue therapy for grade 2 or higher autonomic neuropathy causing constipation.
The safety and efficacy of vinorelbine have not been established in children or infants. In a single-arm trial in pediatric patients (median, 11 years; range, 1 to 25 years) with recurrent solid malignant tumors (n = 46), monotherapy with vinorelbine resulted in an objective tumor response in 2 of 21 patients with rhabdomyosarcoma or undifferentiated sarcoma; no objective tumor response was observed in patients with central nervous system tumors or neuroblastoma. The most significant grade 3 or 4 adverse reactions were neutropenia (70%), anemia (33%), motor neuropathy (15%), cranial neuropathy (13%), hypoxia (13%), and dyspnea (11%).
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.
Counsel patients about the reproductive risk and contraception requirements during vinorelbine treatment. Vinorelbine can be teratogenic if taken by the mother during pregnancy. Females should avoid pregnancy and should use highly effective contraception during and for at least 6 months after treatment with vinorelbine. Females of reproductive potential should undergo pregnancy testing prior to initiation of vinorelbine. Women who become pregnant while receiving vinorelbine should be apprised of the potential hazard to the fetus. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should use highly effective contraception during treatment and for 3 months after completion of therapy with vinorelbine. Although there are no data regarding the effect of vinorelbine on human fertility, male infertility has been observed in animal studies.
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.
For the treatment of non-small cell lung cancer (NSCLC):
-for adjuvant treatment of resected non-small cell lung cancer (NSCLC) in combination with cisplatin*:
Intravenous dosage:
Adults: 25 or 30 mg/m2 IV once weekly for up to 16 doses in combination with cisplatin 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. 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.
-for the treatment of metastatic non-small cell lung cancer (NSCLC), as monotherapy:
Intravenous dosage:
Adults: 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.
-for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with every-4-week cisplatin:
Intravenous dosage:
Adults: 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.
-for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with every-6-week cisplatin:
Intravenous dosage:
Adults: 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.
-for the first-line treatment of advanced non-small cell lung cancer (NSCLC) in combination with cisplatin and cetuximab*:
Intravenous dosage:
Adults: 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%). 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.
For the treatment of metastatic breast cancer*:
-for the treatment of metastatic breast cancer, in patients previously treated with anthracyline and/or taxane therapy*:
Intravenous dosage:
Adults: 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.
-for the treatment of HER2-positive metastatic breast cancer in combination with trastuzumab*:
Intravenous dosage:
Adults: 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.
-for the treatment of HER2-positive, trastuzumab-resistant, advanced breast cancer in patients previously treated with a taxane, in combination with trastuzumab and everolimus*:
Intravenous dosage:
Adults: 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.
For the treatment of recurrent ovarian cancer*:
Intravenous dosage:
Adults: 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%). 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.
For the treatment of recurrent or metastatic squamous cell head and neck cancer*:
Intravenous dosage:
Adults: 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.
For the treatment of desmoid tumor* or aggressive fibromatosis, in combination with methotrexate:
Intravenous dosage:
Adults: 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).
Infants >= 1 month, Children, and Adolescents: 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).
For the treatment of relapsed or refractory Hodgkin lymphoma*, in combination with other chemotherapy agents:
Intravenous dosage:
Adults: 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.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicity
Constipation
-Grade 2 or higher autonomic neuropathy causing constipation: Discontinue vinorelbine therapy.
Hematologic Toxicity
For patients WITHOUT prior fever or sepsis with absolute neutrophil count (ANC) less than 1,500 cells/mm3, and no more than 1 dose held due to neutropenia:
-ANC 1,500 cells/mm3 or more on the day of treatment: No dose adjustment necessary.
-ANC 1,000 to 1,499 cells/mm3 on the day of treatment: Reduce the dose of vinorelbine to 50% of the starting dose.
-ANC less than 1,000 cells/mm3 on the day of treatment: Do not administer vinorelbine. Repeat neutrophil count in 1 week. If 3 consecutive weekly doses are held due to an ANC less than 1,000 cells/mm3, discontinue vinorelbine.
For patients WITH prior fever or sepsis with ANC less than 1,500 cells/mm3, or for patients with 2 consecutive weekly doses held due to neutropenia:
-ANC 1,500 cells/mm3 or more on the day of treatment: Reduce subsequent doses of vinorelbine to 75% of the starting dose.
-ANC 1,000 to 1,400 cells/mm3 on the day of treatment: Reduce subsequent doses of vinorelbine to 37.5% of the starting dose.
-ANC less than 1,000 cells/mm3 on the day of treatment: Do not administer vinorelbine. Repeat neutrophil count in 1 week.
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.
Peripheral Neuropathy
-Grade 2 or higher: Discontinue vinorelbine treatment.
Pulmonary Toxicity
-Hold vinorelbine therapy in patients who develop unexplained dyspnea or have any evidence of pulmonary toxicity. Permanently discontinue vinorelbine in patients with confirmed interstitial pneumonitis or acute respiratory distress syndrome (ARDS).
For patients with prior fever or sepsis with absolute neutrophil count (ANC) less than 1,500 cells/mm3, or for patients who had 2 consecutive weekly doses held due to neutropenia:
Maximum Dosage Limits:
-Adults
30 mg/m2 IV.
-Elderly
30 mg/m2 IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
-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.
Patients with Renal Impairment Dosing
No dosage adjustment necessary.
*non-FDA-approved indication
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 CYP3A substrate and amiodarone is a weak CYP3A 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.
Bacillus Calmette-Guerin Vaccine, BCG: (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.
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.
Capivasertib: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with capivasertib is necessary. Vinorelbine is a CYP3A substrate and capivasertib is a weak CYP3A 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.
Chikungunya Vaccine, Live: (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.
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.
Daridorexant: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with daridorexant is necessary. Vinorelbine is a CYP3A substrate and daridorexant is a weak CYP3A 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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
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.
Fexinidazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with fexinidazole is necessary. Vinorelbine is a CYP3A substrate and fexinidazole is a weak CYP3A 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.
Intranasal Influenza Vaccine: (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.
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.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (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.
Measles/Mumps/Rubella Vaccines, MMR: (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.
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.
Rotavirus Vaccine: (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.
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.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (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.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (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.
Smallpox Vaccine, Vaccinia Vaccine: (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.
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.
Typhoid Vaccine: (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.
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.
Varicella-Zoster Virus Vaccine, Live: (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.
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: (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: (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.
Yellow Fever Vaccine, Live: (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.
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.
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.
Affected cytochrome P450 (CYP) isoenzymes and drug transporters: CYP3A and P-glycoprotein (P-gp)
Vinorelbine is a CYP3A and a P-gp substrate.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of vinorelbine has not been evaluated.
Geriatric
Age does not affect the clearance, volume of distribution, or half-life of vinorelbine.