Vincristine should be administered by individuals experienced in the administration of vincristine.
It is extremely important that the IV needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during IV administration may cause considerable irritation. If extravasation occurs, discontinue the injection immediately and then introduce any remaining portion of the dose into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage will help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis.
For IV use only. Fatal if given by other routes. See "Additional Information/Pharmacotherapy Pearls" for treatment of patients given (inadvertent) intrathecal administration of vincristine.
Note: Dispense vincristine in a minibag or other flexible plastic container (NOT in a syringe) (ISMP 2020). Some doses may be capped at a maximum of 2 mg/dose; refer to protocol. Dosing and frequency may vary by protocol and/or treatment phase. Patients receiving vincristine should be on a prophylactic bowel management regimen to prevent constipation.
Acute lymphocytic leukemia:
CALGB 10403 regimen: Patients <40 years of age: IV: Induction phase: 1.5 mg/m2 (maximum: 2 mg) on days 1, 8, 15, and 22; Extended remission induction phase (if required): 1.5 mg/m2 (maximum: 2 mg) on day 1 and 8; Remission consolidation phase: 1.5 mg/m2 (maximum: 2 mg) on days 15, 22, 43, and 50; Delayed intensification phase: 1.5 mg/m2 (maximum: 2 mg) on days 1, 8, 43, and 50; Maintenance phase: 1.5 mg/m2 (maximum: 2 mg) on days 1, 29, and 57 of a 12-week cycle; continue maintenance phase until 2 years (females) or 3 years (males) from start of interim maintenance; phases are part of combination chemotherapy; refer to protocol for details (Stock 2019).
DFCI Consortium regimen: Patients ≤50 years of age: IV: Induction phase: 2 mg on days 1, 8, 15, and 22 (4-week treatment cycle); CNS therapy phase: 2 mg for one dose (3-week treatment cycle); Intensification phase: 2 mg on day 1 (3-week cycle; continue for 30 weeks); Continuation phase: 2 mg on day 1 (3-week cycle; continue for 74 weeks); phases are part of combination chemotherapy; refer to protocol for details (DeAngelo 2015).
Hyper-CVAD regimen: IV: 2 mg on days 4 and 11 during odd-numbered cycles (cycles 1, 3, 5, 7 [in combination with cyclophosphamide, mesna, doxorubicin, and dexamethasone]) of an 8-cycle phase, followed by maintenance treatment (if needed) of 2 mg once monthly for 2 years (Kantarjian 2004), plus a tyrosine kinase inhibitor (for Philadelphia chromosome-positive disease) (Ravandi 2010; Thomas 2004).
CALBG 8811 regimen: IV: Induction phase: 2 mg on days 1, 8, 15, and 22 (4-week treatment cycle); Early intensification phase: 2 mg on days 15 and 22 (4-week treatment cycle, repeat once); Late intensification phase: 2 mg on days 1, 8, and 15 (8-week treatment cycle); Maintenance phase: 2 mg on day 1 every 4 weeks until 24 months from diagnosis; phases are part of combination chemotherapy; refer to protocol for details (Larson 1995).
GRAALL 2003 regimen: Patients <60 years of age: IV: Induction phase: 2 mg on days 1, 8, 15, and 22; Consolidation phase: 2 mg on day 15 of consolidation blocks 2, 5, and 8; Late intensification phase: 2 mg on days 1, 8, and 15; Maintenance phase: 2 mg on day 1 every month for 12 months; phases are part of combination chemotherapy; refer to protocol for further information (Huguet 2009).
GRAALL 2005 regimen: Patients <60 years of age: IV: Induction phase: 2 mg on days 1, 8, 15, and 22; Interphase-1: 2 mg on day 1; First, second, and third consolidation phases (block 2, block 5, and block 8, respectively): 2 mg on day 15; Late intensification phase (if complete response after first course): 2 mg on days 1, 8, 15, and 22; Maintenance phase: 2 mg on day 1 monthly for 12 months; phases are part of combination chemotherapy; refer to protocol for further information (Huguet 2018).
MRC UKALL XII/ECOG E2993: Patients <60 years of age: IV: Induction (phase 1): 1.4 mg/m2 on days 1, 8, 15, and 22; Consolidation phase (cycle 1): 1.4 mg/m2 on days 1, 8, 15, and 22; Maintenance phase: 1.4 mg/m2 once every 3 months; continue maintenance for 2.5 years from the start of intensification; phases are part of combination chemotherapy; refer to protocol for further information (Rowe 2005).
Philadelphia chromosome-positive acute lymphoblastic lymphoma:
Kim 2015: IV: 2 mg on days 1 and 8 of induction and consolidation A cycles (in combination with daunorubicin, prednisolone, cytarabine, etoposide, methotrexate, leucovorin, and nilotinib); refer to protocol for further information.
Rousselot 2016:
Patients ≥55 to ≤70 years of age: Induction: IV: 2 mg once weekly for 4 weeks (in combination with dexamethasone and dasatinib); refer to protocol for further information.
Patients >70 years of age: Induction: IV: 1 mg once weekly for 4 weeks (in combination with dexamethasone and dasatinib); refer to protocol for further information.
Central nervous system tumors (off-label use):
Anaplastic oligodendroglioma/astrocytomas, low-grade gliomas: PCV regimen (in combination with procarbazine, lomustine, and radiation therapy): IV: 1.4 mg/m2 (some protocols cap the vincristine dose at 2 mg; refer to protocols for details) on days 8 and 29 of a 6- to 8-week treatment cycle for 4 to 6 cycles (Buckner 2016; Cairncross 2006; Cairncross 2013; Shaw 2012; van den Bent 2006; van den Bent 2013).
Glioblastoma, recurrent: PCV regimen (in combination with procarbazine and lomustine): IV: 1.4 mg/m2 (maximum: 2 mg) on days 8 and 29 of a 6-week cycle for 7 cycles (Levin 2000) or 1.5 mg/m2 (maximum: 2 mg) on day 1 of a 6-week cycle for up to 6 cycles (Brada 2010).
Medulloblastoma: Adults ≤21 years of age: IV: 1.5 mg/m2 (maximum dose: 2 mg) weekly for a maximum of 8 doses (in combination with radiation, cisplatin, and either lomustine or cyclophosphamide) (Packer 2006).
Chronic lymphocytic leukemia/small lymphocytic leukemia, with Richter transformation (off-label use): IV: 2 mg (flat dose) days 4 and 11 of courses 1, 3, 5, and 7 (in combination with cyclophosphamide, mesna, doxorubicin, and dexamethasone [± rituximab]) and alternates with even courses 2, 4, 6, and 8 (methotrexate, leucovorin, and cytarabine) (Thomas 2006; Tsimberidou 2003) or 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide, doxorubicin, and prednisone [± rituximab]) (Coiffier 2002; Tsimberidou 2006).
Ewing sarcoma (off-label use): VDC/IE regimen: VDC: IV: 2 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle (in combination with doxorubicin and cyclophosphamide), alternates with IE (ifosfamide and etoposide) for a total of 17 cycles (Grier 2003).
Gestational trophoblastic tumors, high-risk (off-label use): EMA/CO regimen: IV: 1 mg/m2 on day 8 of a 2-week treatment cycle (in combination with etoposide, methotrexate, leucovorin, dactinomycin, and cyclophosphamide), continue for at least 2 treatment cycles after a normal hCG level (Escobar 2003; Lurain 2006).
Hodgkin lymphoma:
BEACOPP (standard or escalated) regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 8 of a 21-day treatment cycle (in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, procarbazine, and prednisone) for 8 cycles (Diehl 2003).
Stanford-V regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) in weeks 2, 4, 6, 8, 10, and 12 (in combination with mechlorethamine, vinblastine, bleomycin, doxorubicin, etoposide, and prednisone) (Horning 2000; Horning 2002).
Merkel cell carcinoma, advanced or recurrent (off-label use; based on limited data): CAV regimen: IV: 2 mg on day 1 every 21 days (in combination with cyclophosphamide and doxorubicin) (Fenig 1997).
Multiple myeloma (off-label use):
DVD regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 28-day treatment cycle (in combination with pegylated doxorubicin and dexamethasone) (Rifkin 2006).
VAD regimen: IV: 0.4 mg/day continuous infusion for 4 days (over 96 hours) (total 1.6 mg/cycle) of a 28-day treatment cycle (in combination with conventional doxorubicin and dexamethasone) (Rifkin 2006).
Non-Hodgkin lymphoma:
Burkitt lymphoma:
CALGB 10002 regimen (cycles 2 through 7): IV: 2 mg on day 1 every 3 weeks (in combination with cyclophosphamide, prednisone, ifosfamide, dexamethasone, methotrexate, leucovorin, cytarabine, etoposide, rituximab, doxorubicin, intrathecal therapy, and filgrastim); refer to protocol for details (Rizzieri 2014).
CODOX-M/IVAC: Cycles 1 and 3 (CODOX-M): IV: 1.5 mg/m2 (no maximum dose) days 1 and 8 of cycle 1 and days 1, 8, and 15 of cycle 3 (Magrath 1996) or 1.5 mg/m2 (maximum dose: 2 mg) days 1 and 8 of cycles 1 and 3 (Mead 2002; Mead 2008); CODOX-M is in combination with cyclophosphamide, doxorubicin, methotrexate, and CNS prophylaxis and alternates with IVAC (etoposide, ifosfamide, mesna, cytarabine, and CNS prophylaxis) for a total of 4 cycles.
R-Hyper-CVAD: IV: 2 mg (flat dose) days 4 and 11 of courses 1, 3, 5, and 7 (in combination with rituximab, cyclophosphamide, doxorubicin, and dexamethasone) and alternates with even courses 2, 4, 6, and 8 (rituximab, methotrexate and cytarabine) (Thomas 2006).
Diffuse large B-cell lymphoma:
CHOP/R-CHOP regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle for 8 cycles (in combination with cyclophosphamide, doxorubicin, and prednisone [± rituximab]) (Coiffier 2002).
Dose-adjusted EPOCH/EPOCH-R regimen: IV: 0.4 mg/m2/day continuous infusion for 4 days (over 96 hours) (total 1.6 mg/m2/cycle; dose not usually capped) of a 21-day treatment cycle (in combination with etoposide, prednisone, cyclophosphamide, and doxorubicin, ± rituximab) (García-Suárez 2007; Wilson 2002).
R-CEOP regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle for 3 to 6 cycles (in combination with rituximab, cyclophosphamide, etoposide, and prednisone) (Moccia 2009).
Follicular lymphoma:
CVP regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide and prednisone [± rituximab or obinutuzumab]) for 8 cycles (Marcus 2005; Marcus 2017).
R-CHOP regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle for 6 to 8 cycles (in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone) (Hiddemann 2005).
Peripheral T-cell lymphoma:
CHOEP regimen: IV: 2 mg on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone) for 6 to 8 cycles (Pfreundschuh 2004; Schmitz 2010).
CHOP regimen: IV: 1.4 mg/m2 (maximum dose: 2 mg) on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide, doxorubicin, and prednisone) (Schmitz 2010).
Primary mediastinal B-cell lymphoma: DA-EPOCH-R regimen: IV: 0.4 mg/m2/day (no cap) as a continuous infusion on days 1 to 4 (over 96 hours) dose-adjusted for subsequent cycles based on neutrophil and platelet counts during nadir (in combination with etoposide, prednisone, cyclophosphamide, doxorubicin, rituximab, and filgrastim); repeat cycle every 3 weeks for a total of 6 to 8 cycles (Dunleavy 2013)
Ovarian cancer (off-label use): VAC regimen: IV: 1.5 mg/m2 (maximum dose: 2 mg) once weekly for 8 to 12 weeks (in combination with dactinomycin and cyclophosphamide) (Slayton 1985)
Pheochromocytoma, malignant (off-label use; based on limited data): IV: 1.4 mg/m2 on day 1 every 3 or 4 weeks (in combination with cyclophosphamide and dacarbazine) (Huang 2008)
Primary CNS lymphoma (off-label use): R-MPV regimen: Induction: IV: 1.4 mg/m2 (maximum dose: 2.8 mg or per standard of practice) on day 1 or day 2 of a 14-day cycle for 5 to 7 cycles (in combination with rituximab, high-dose methotrexate, leucovorin, and procarbazine), followed by reduced-dose whole brain radiotherapy and cytarabine (Morris 2013; Shah 2007) or autologous stem cell transplant (Omuro 2015). Two additional cycles of R-MPV may be administered to patients with partial response after initial induction chemotherapy; refer to protocols for details.
Rhabdomyosarcoma:
VAC regimen: Patients <50 years: IV: 1.5 mg/m2 (maximum dose: 2 mg) once weekly per protocol; duration of therapy depends on risk status (in combination with dactinomycin, cyclophosphamide, and mesna) (Raney 2011)
VA regimen: Patients <50 years: IV: 1.5 mg/m2 (maximum dose: 2 mg) once weekly per protocol (Raney 2011)
Small cell lung cancer, recurrent (off-label use): CAV regimen: IV: 2 mg/dose on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide and doxorubicin) (von Pawel 1999)
Thymoma, advanced (off-label use; based on limited data): ADOC regimen: IV: 0.6 mg/m2 on day 3 every 3 weeks (in combination with cisplatin, doxorubicin, and cyclophosphamide) (Fornasiero 1991)
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. IV: 1.4 mg/m2/dose; frequency may vary based on indication and/or protocol.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary (Kintzel 1995; Krens 2019).
Hemodialysis: No dosage adjustment is expected (Krens 2019).
The manufacturer’s labeling recommends the following adjustment: Serum bilirubin >3 mg/dL: Administer 50% of normal dose.
The following adjustments have also been recommended:
Floyd 2006: Serum bilirubin 1.5 to 3 mg/dL or transaminases 2 to 3 times ULN or alkaline phosphatase increased: Administer 50% of dose.
Superfin 2007:
Serum bilirubin 1.5 to 3 mg/dL: Administer 50% of dose.
Serum bilirubin >3 mg/dL: Avoid use.
(For additional information see "Vincristine (conventional): Pediatric drug information")
Note: Doses are almost always capped at a maximum of 2 mg/dose/week (Kushner 2010). Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. In pediatric patients, dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precaution to verify dosing parameters during calculations. For infants and children <10 kg, dosing is typically reduced (eg, 30% reduction); refer to specific protocols (Rubie 2011). The World Health Organization (WHO) and the Institute for Safe Medication Practices (ISMP) strongly recommend dispensing vincristine in a minibag (NOT in a syringe) (ISMP 2020).
Acute lymphocytic leukemia (ALL) of infancy: Limited data available: Infants <1 year of age at diagnosis: IV: 1.5 mg/m2/dose; maximum dose: 2 mg/dose; reported frequency variable but not more frequently than weekly
Pieters 2007: Interfant-99 protocol: Administer on the following days: Induction phase: Days 8, 15, 22, and 29 (in combination with prednisone, dexamethasone, cytarabine, daunorubicin, l-asparaginase, and CNS intrathecal prophylaxis); Reinduction: Days 1, 8, 15, and 22 (in combination with dexamethasone, 6-thioguanine, daunorubicin, cytarabine, cyclophosphamide, and CNS intrathecal prophylaxis)
Acute lymphocytic leukemia (ALL), standard risk and high risk: Limited data available: Children and Adolescents: IV: 1.5 mg/m2/dose; maximum dose: 2 mg/dose; reported frequency variable but not more frequent than weekly:
Standard risk:
Avramis 2002: Administer dose on the following days: Induction phase: Days 0, 7, 14, and 21; Consolidation phase: Days 0, 28, and 56; Interim maintenance phases: Days 0 and 28; Delayed intensification phase: Days 0, 7, and 14; Maintenance phase: Every 4 weeks
Bostrom 2003: Administer dose on the following days: Induction phase: Days 0, 7, 14, and 21; Consolidation phase: Days 0, 28, and 56; Delayed intensification phase: Days 0, 7, and 14; Maintenance phase: Days 0, 28, and 56
High risk: Larsen 2016: Administer on the following days: Induction phase: Days 1, 8, 15, and 22; Extended Induction: Days 1 and 8; Consolidation: Days 15, 22, 43, and 50; Interim Maintenance 1: Days 1, 15, 29, and 42; Interim Maintenance 2: Days 1, 11, 21, 31, and 41; Delayed Intensification 1: Days 1, 8, 15, 43, and 50; Delayed Intensification 2: Days 1, 8, 15, 43, and 50; Maintenance phase: Every 4 weeks
Ewing sarcoma: Limited data available: Children and Adolescents: Dose and frequency regimens variable:
Grier 2003: IV: 2 mg/m2/dose on day 1 of a 21-day cycle, administer either every cycle or during odd-numbered cycles (VDC/IE regimen); maximum dose: 2 mg/dose
Kolb 2003: IV: 0.67 mg/m2/day as a continuous IV infusion on days 1, 2, and 3; total dose for cycle: 2 mg/m2/cycle (maximum dose/cycle: 2 mg/dose/cycle) during cycles 1, 2, 3, and 6
Hepatoblastoma: Limited data available: Infants, Children, and Adolescents: C5V Regimen: IV: 1.5 mg/m2/dose on Day 2 of a 3-week treatment cycle for 4 cycles (in combination with 5-fluorouracil and cisplatin (Ortega 2000)
Hodgkin lymphoma: Limited data available: Children and Adolescents:
AV-PC (low-risk regimen): IV: 1.4 mg/m2/dose (maximum dose: 2.8 mg/dose) on Day 1 and 8 of a 21-day treatment cycle for 3 cycles (in combination with doxorubicin, prednisone, and cyclophosphamide) (Appel 2016)
ABVE-PC (high-risk and intermediate regimens): IV: 1.4 mg/m2/dose (maximum dose: 2.8 mg/dose) on Day 1 and 8 of a 21-day treatment cycle for 3 to 5 cycles (in combination with doxorubicin, bleomycin, etoposide, cyclophosphamide, and prednisone) (Friedman 2014; Schwartz 2009)
BEACOPP regimen (high-risk regimen): IV: 2 mg/m2/dose on day 7 of a 21-day treatment cycle for 4 cycles (in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, procarbazine, and prednisone); maximum dose: 2 mg/dose (Kelly 2002)
Low-grade glioma, CNS tumor (low-grade ependymoma, infantile desmoplastic astrocytoma, etc): Limited data available: Children <10 years: IV: 1.5 mg/m2/dose; maximum dose: 2 mg/dose; reported combination chemotherapy and frequency variable but not more frequent than weekly:
Ater 2012: CV regimen: Administer on the following days: Induction phase: Days 0, 7, 14, 21, 28, 35, 42, 49, 56, and 63 of an 84-day cycle (in combination with carboplatin); Maintenance phase: Day 0, 7, and 14 of a 42-day cycle for 8 cycles (in combination with carboplatin)
Ater 2012: TPCV regimen: Administer on days 14 and 28 of a 42-day cycle (in combination with thioguanine, procarbazine, and lomustine) for a total of 8 cycles
Medulloblastoma: Limited data available:
Average-risk regimen: Children ≥3 years and Adolescents: IV: 1.5 mg/m2/dose (maximum dose: 2 mg/dose) once weekly during radiation therapy for up to 8 doses followed by 1.5 mg/m2/dose (maximum dose: 2 mg/dose) on days 1, 7, and 14 per cycle (in combination with cisplatin and either lomustine or cyclophosphamide) for 8 cycles (Packer 2006)
High risk: Head Start II Protocol: Children <10 years: IV: 0.05 mg/kg/dose on Days 1, 8, and 15 of a 21-day cycle in cycles 1 to 3 only (9 total doses in combination with cisplatin, etoposide, cyclophosphamide, methotrexate) (Chi 2004)
Neuroblastoma: Limited data available:
Infants:
Low-dose cyclophosphamide-vincristine regimen: IV: 0.05 mg/kg/dose vincristine on day 1, and repeat in 14 days (Rubie 2003)
CAdO regimen: IV: 0.05 mg/kg/dose on day 1 and 5 and repeated in 21 days (in combination with cyclophosphamide and doxorubicin) (Rubie 2003; Rubie 2011)
Children and Adolescents:
High risk: Induction therapy: IV: 1.5 mg/m2/dose Day 1 in combination with doxorubicin and cyclophosphamide for cycles 2 and 5 (Seif 2013)
Refractory: HD-CTV regimen: IV: 0.067 mg/kg/dose or 2 mg/m2/dose, whichever is lower; maximum dose: 2 mg/dose on day 1 (Kushner 2010)
Non-Hodgkin Lymphomas:
Burkitt lymphoma, Diffuse large B-cell lymphoma and B-cell ALL: Limited data available:
Cairo 2007, Goldman 2013, Goldman 2014: Children and Adolescents:
Reduction (COP regimen): IV: 1 mg/m2/dose; maximum dose: 2 mg/dose on Day 1 (in combination with cyclophosphamide, prednisone, and intrathecal methotrexate)
Induction 1 and 2 (COPADM regimen): IV: 2 mg/m2/dose; maximum dose: 2 mg/dose on Day 1 (in combination with cyclophosphamide, prednisone, doxorubicin, methotrexate, and intrathecal methotrexate)
Maintenance 1 (COPAM regimen) and 3 (COPA regimen): IV: 2 mg/m2/dose; maximum dose: 2 mg/dose on Day 1 (in combination with cyclophosphamide, prednisone, doxorubicin, and methotrexate [maintenance 1 only])
Reiter 1999: Children and Adolescents: IV: 1.5 mg/m2/dose; maximum dose: 2 mg/dose; administer dose on day 1 of cycle AA (in combination with dexamethasone, ifosfamide, methotrexate, cytarabine, etoposide, and CNS prophylaxis) and on day 1 of cycle BB (in combination with dexamethasone, cyclophosphamide, methotrexate, doxorubicin, and CNS prophylaxis)
Primary mediastinal B-cell Lymphoma (PMBCL): Limited data available:
DA-EPOCH-R regimen: Children ≥9 years and Adolescents: IV: 0.4 mg/m2/day as a continuous infusion over 96 hours on days 1 to 4 (in combination with rituximab, doxorubicin, etoposide, cyclophosphamide, prednisone, and filgrastim); no maximum dose. Doses for subsequent cycles are based on neutrophil and platelet counts; repeat cycle every 3 weeks for a total of 6 to 8 cycles (Dunleavy 2013; Giulino-Roth 2017; Woessmann 2013)
Retinoblastoma: Limited data available:
Infants and Children ≤36 months: IV: 0.05 mg/kg/dose (maximum dose: 2 mg/dose); reported frequency variable but not more frequent than weekly
Rodriguez-Galindo 2003: Administer dose on day 1 every 21 days in combination with carboplatin for 8 cycles
Friedman 2000: Administer dose day 0 every 28 days in combination with carboplatin and etoposide for 6 cycles
Children >36 months: IV: 1.5 mg/m2 (maximum dose: 2 mg/dose) on day 0 every 28 days in combination with carboplatin and etoposide for 6 cycles (Friedman 2000)
Rhabdomyosarcoma: Limited data available (Raney 2011; Walterhouse 2011; Walterhouse 2014); reported frequency variable but not more frequent than weekly: Duration of therapy depends on risk status; VA (in combination with dactinomycin) or VAC regimen (in combination with dactinomycin and cyclophosphamide):
Infants: IV: 0.025 mg/kg/dose
Children 1 to <3 years: IV: 0.05 mg/kg/dose
Children ≥3 years and Adolescents: IV: 1.5 mg/m2/dose (maximum dose: 2 mg/dose)
Wilms tumor: Limited data available (Green 2007):
Infants and Children weighing ≤30 kg: IV: 0.05 mg/kg/dose (maximum dose: 2 mg/dose) weeks 1, 2, 4, 5, 6, 7, 8, 10, and 11, followed by 0.067 mg/kg/dose (maximum dose: 2 mg/dose) weeks 12, 13, 18, and 24 (in combination with doxorubicin, cyclophosphamide, mesna, etoposide, and filgrastim)
Children and Adolescents weighing >30 kg: IV: 1.5 mg/m2/dose (maximum dose: 2 mg) weeks 1, 2, 4, 5, 6, 7, 8, 10, and 11, followed by 2 mg/m2/dose (maximum dose: 2 mg) weeks 12, 13, 18, and 24 (in combination with doxorubicin, cyclophosphamide, mesna, etoposide, and filgrastim)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric specific recommendations; consult individual protocols; based on experience in adult patients, dosing adjustment may not be necessary.
All patients: The manufacturer's labeling recommends the following adjustment: Serum bilirubin >3 mg/dL: Administer 50% of normal dose.
The following adjustments have also been recommended:
Floyd 2006: Serum bilirubin 1.5 to 3 mg/dL or transaminases 2 to 3 times ULN or alkaline phosphatase increased: Administer 50% of dose.
Superfin 2007:
Serum bilirubin 1.5 to 3 mg/dL: Administer 50% of dose.
Serum bilirubin >3 mg/dL: Avoid use.
Refer to adult dosing.
ASCO guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: The practice of limiting vincristine doses to 2 mg is not supported by current clinical data. Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing with subsequent cycles, if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved (ASCO [Griggs 2021]).
Constipation (including upper colon impaction): May require high enemas and laxatives.
Progressive dyspnea with pulmonary dysfunction: Permanently discontinue vincristine.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as sulfate [preservative free]:
Vincasar PFS: 1 mg/mL (1 mL, 2 mL)
Generic: 1 mg/mL (1 mL, 2 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as sulfate:
Generic: 1 mg/mL (1 mL, 2 mL, 5 mL)
For IV administration only. Fatal if given by other routes.
Dispense vincristine in a minibag or other flexible plastic container (NOT in a syringe) (ISMP 2020). Vincristine should NOT be delivered to the patient at the same time with any medications intended for CNS administration.
IV: Preferred administration is as a short 5- to 10-minute infusion in a 25 to 50 mL minibag. Some protocols utilize a 24-hour continuous infusion (off-label rate). The minibag may be infused directly into an IV catheter or into a running IV infusion line.
Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry warm compresses for 20 minutes 4 times a day for 1 to 2 days; elevate (ESMO/EONS [Perez Fidalgo 2012]). Remaining portion of the vincristine dose should be infused through a separate vein.
Hyaluronidase: If needle/cannula still in place, administer 1 to 6 mL hyaluronidase (150 units/mL) into the existing IV line; the usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug (ESMO/EONS [Perez Fidalgo 2012]; Schulmeister 2011). If needle/cannula was removed, inject 1 to 6 mL (150 units/mL) subcutaneously in a clockwise manner using 1 mL for each 1 mL of drug extravasated (Schulmeister 2011) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) subcutaneously into the extravasation site (Polovich 2009).
Note: For IV administration only; fatal if given intrathecally; vincristine should NOT be delivered to the patient with any medications intended for central nervous system (ie, intrathecal) administration. Note: In order to prevent inadvertent intrathecal administration, the World Health Organization (WHO) and the Institute for Safe Medical Practices (ISMP) recommend dispensing vincristine in a minibag (rather than a syringe) (ISMP 2020). Vincristine should NOT be prepared during the preparation of any intrathecal medication. After preparation, keep vincristine in a location away from the separate storage location recommended for intrathecal medications.
IV infusion: Administer minibag dose as a short infusion, generally over 5 to 15 minutes (Gilbar 2015); administration via gravity instead of infusion pump has also been utilized (Beaver 2018). Some protocols utilize a 24-hour continuous IV infusion.
Vincristine is a vesicant and should only be administered IV; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote (see Management of Drug Extravasations for more details); apply dry warm compresses for 20 minutes 4 times a day for 1 to 2 days; elevate extremity (Pérez Fidalgo 2012). Remaining portion of the vincristine dose should be infused through a separate vein.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute lymphocytic leukemia: Treatment of acute lymphocytic leukemia.
Hodgkin lymphoma: Treatment of Hodgkin lymphoma.
Neuroblastoma: Treatment of neuroblastoma.
Non-Hodgkin lymphomas: Treatment of non-Hodgkin lymphomas.
Rhabdomyosarcoma: Treatment of rhabdomyosarcoma.
Wilms tumor: Treatment of Wilms tumor.
Central nervous system tumors (anaplastic oligodendrogliomas/oligoastrocytomas, low-grade gliomas, medulloblastoma, recurrent glioblastoma); Chronic lymphocytic leukemia/small lymphocytic lymphoma with Richter transformation; Ewing sarcoma; Gestational trophoblastic tumors, high risk; Merkel cell carcinoma (advanced or recurrent); Multiple myeloma; Ovarian germ cell tumors; Pheochromocytoma, malignant; Primary CNS lymphoma; Small cell lung cancer (recurrent); Thymoma, advanced
VinCRIStine may be confused with vinBLAStine, vinorelbine
VinCRIStine conventional may be confused with vinCRIStine liposomal
Oncovin may be confused with Ancobon
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
For IV use only. Fatal if administered by other routes. To prevent fatal inadvertent intrathecal injection, dispense vincristine doses in a flexible plastic container (eg, diluted in 25 to 50 mL of a compatible solution), and NOT a syringe (ISMP 2020). Vincristine should NOT be prepared during the preparation of any medications intended for CNS administration. After preparation, keep vincristine in a location away from the separate storage location recommended for medications intended for CNS administration. Vincristine should NOT be delivered to the patient at the same time with any medications intended for CNS administration.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
<1%: Endocrine & metabolic: SIADH
Frequency not defined:
Cardiovascular: Hypertension, hypotension
Dermatologic: Alopecia (common)
Endocrine & metabolic: Dehydration, hyperuricemia, weight loss
Gastrointestinal: Abdominal cramps, anorexia, constipation (may involve upper colon fecal impaction), diarrhea, intestinal necrosis, intestinal perforation, nausea, oral mucosa ulcer, paralytic ileus, vomiting
Genitourinary: Bladder dysfunction (atony), dysuria
Hematologic & oncologic: Leukopenia
Nervous system: Abnormal gait, abnormal sensory symptoms (loss of), cranial nerve disorder (including impairment of extraocular movement, laryngeal muscle impairment, paresis, vocal cord paralysis), decreased deep tendon reflex, headache, neuritic pain, paresthesia, sensorimotor neuropathy (dysfunction)
Neuromuscular & skeletal: Amyotrophy, foot-drop (including slap gait)
Renal: Polyuria
Miscellaneous: Fever
Postmarketing:
Dermatologic: Skin rash
Endocrine & metabolic: Uric acid nephropathy (acute)
Gastrointestinal: Sore throat
Hematologic & oncologic: Anemia, thrombocytopenia
Nervous system: Ataxia, paralysis, parotid pain, seizure
Neuromuscular & skeletal: Back pain, jaw pain, limb pain, myalgia, ostealgia
Ophthalmic: Blepharoptosis (Hatzipantelis 2015; Revannasiddaiah 2011), cortical blindness (transient), optic atrophy (with blindness)
Respiratory: Acute respiratory distress syndrome
Patients with the demyelinating form of Charcot-Marie-Tooth syndrome
Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Extravasation: Vincristine is a vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. Individuals administering should be experienced in vincristine administration. Extravasation may cause significant irritation. If extravasation occurs, discontinue immediately and initiate appropriate extravasation management, including local injection of hyaluronidase and moderate heat application to the affected area. Use a separate vein to complete administration.
• Gastrointestinal effects: Constipation, paralytic ileus, intestinal necrosis and/or perforation may occur; constipation may present as upper colon impaction with an empty rectum (may require flat film of abdomen for diagnosis); generally responds to high enemas and laxatives. All patients should be on a prophylactic bowel management regimen.
• Neurotoxicity: Alterations in mental status such as depression, confusion, or insomnia may occur; neurologic effects are dose-limiting (may require dosage reduction) and may be additive with those of other neurotoxic agents and spinal cord irradiation. Use with caution in patients with pre-existing neuromuscular disease and/or with concomitant neurotoxic agents.
• Respiratory effects: Acute shortness of breath and severe bronchospasm have been reported with vinca alkaloids, usually when used in combination with mitomycin. Onset may be several minutes to hours after vincristine administration and up to 2 weeks after mitomycin. Progressive dyspnea may occur.
• Uric acid nephropathy: Acute uric acid nephropathy has been reported with vincristine.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment. Vincristine may be associated with hepatic sinusoidal obstruction syndrome (formerly called veno-occlusive disease), increased risk in children <3 years of age; use with caution in hepatobiliary dysfunction.
Other warnings/precautions:
• For IV use only: For IV administration only; fatal if given by other routes. To prevent administration errors, dispense vincristine diluted in a minibag (ISMP 2020). Vincristine should NOT be prepared during the preparation of any medications intended for CNS administration. After preparation, keep vincristine in a location away from the separate storage location recommended for medications intended for CNS administration. Vincristine should NOT be delivered to the patient at the same time with any medications intended for CNS administration (ASCO/ONS [Neuss 2016]).
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of VinCRIStine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of VinCRIStine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of VinCRIStine. Management: Seek alternatives to this combination when possible. If combined, monitor closely for vincristine toxicities (eg, neurotoxicity, gastrointestinal toxicity, myelosuppression). Risk D: Consider therapy modification
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fluconazole: May increase the serum concentration of VinCRIStine. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of VinCRIStine. VinCRIStine may decrease the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
MitoMYcin (Systemic): Antineoplastic Agents (Vinca Alkaloids) may enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. Risk C: Monitor therapy
NIFEdipine: May increase the serum concentration of VinCRIStine. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of VinCRIStine. VinCRIStine may decrease the serum concentration of Phenytoin. Management: . Risk C: Monitor therapy
Teniposide: May enhance the neurotoxic effect of VinCRIStine. Risk C: Monitor therapy
Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy
Patients who could become pregnant should avoid becoming pregnant during vincristine treatment.
The effect of vincristine alone on male and female fertility is not known; available information is from use in combination with other agents. Recommendations are available for fertility preservation in patients treated with anticancer agents (ASCO [Oktay 2018]).
Based on data from animal reproduction studies, in utero exposure to vincristine may cause fetal harm. However, use in pregnancy has been described (NTP 2013).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
When multiagent therapy is needed to treat aggressive non-Hodgkin lymphomas during pregnancy, vincristine (as a component of the CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] regimen) may be used when indicated (ESMO [Peccatori 2013]; Lishner 2016).
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (1-877-635-4499).
It is not known if vincristine is present in breast milk.
Vincristine breast milk concentrations were evaluated in one patient following maternal treatment for stage IV diffuse large B-cell lymphoma at 4 months postpartum. Breast milk was sampled over 21 days. Vincristine was not measurable in breast milk; however, due to the high limit of detection, low concentrations could not be excluded (assay limit not described) (Codacci-Pisanelli 2019).
Due to the potential for serious adverse reactions in the breastfed infant, the decision to discontinue vincristine or to discontinue breastfeeding should consider the benefits of treatment to the mother.
Monitor serum electrolytes (sodium), hepatic function tests, CBC with differential, serum uric acid. Monitor for signs or symptoms of hepatic sinusoidal obstruction syndrome, including bilirubin >1.4 mg/dL, unexplained weight gain, ascites, hepatomegaly, or unexplained right upper quadrant pain (Arndt 2004). Monitor infusion site. Perform neurologic examination, monitor for constipation/ileus and for signs/symptoms of peripheral neuropathy.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Vincristine binds to tubulin and inhibits microtubule formation, therefore, arresting the cell at metaphase by disrupting the formation of the mitotic spindle; it is specific for the M and S phases. Vincristine may also interfere with nucleic acid and protein synthesis by blocking glutamic acid utilization.
Note: In pediatric patients, significant intrapatient and interpatient variability has been reported (Gidding 1999).
Distribution: Rapidly removed from bloodstream and tightly bound to tissues; penetrates blood-brain barrier poorly
Metabolism: Extensively hepatic, via CYP3A4
Half-life elimination: Terminal: 85 hours (range: 19 to 155 hours)
Excretion: Feces (~80%); urine (10% to 20%; <1% as unchanged drug)
Clearance: In pediatric patients, correlation with diagnosis has been reported; clearance in patients with ALL and non-Hodgkin lymphoma higher than Wilms’ tumor (Gidding 1999):
Infants: Vincristine clearance is lower compared to children; more closely related to body weight than to body surface area (Crom1994)
Children and Adolescents 2 to 18 years: Reported means: 357 to 482 mL/minute/m2; some suggest faster clearance in children <10 years of age than in adolescents (Crom 1994); however, more recent data does not support this finding nor a dosage reduction in adolescent patients (Frost 2003; Gidding 1999)
Solution (Vincasar PFS Intravenous)
1 mg/mL (per mL): $18.06
Solution (vinCRIStine Sulfate Intravenous)
1 mg/mL (per mL): $6.90 - $7.01
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