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VinCRIStine

Medically reviewed by Drugs.com. Last updated on Jul 24, 2019.

Pronunciation

(vin KRIS teen)

Index Terms

  • Conventional Vincristine
  • Leurocristine Sulfate
  • Oncovin
  • Vincristine (Conventional)
  • Vincristine Sulfate

Dosage Forms

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

Solution, Intravenous, as sulfate [preservative free]:

Vincasar PFS: 1 mg/mL (1 mL [DSC], 2 mL [DSC])

Generic: 1 mg/mL (1 mL, 2 mL)

Brand Names: U.S.

  • Vincasar PFS [DSC]

Pharmacologic Category

  • Antineoplastic Agent, Antimicrotubular
  • Antineoplastic Agent, Vinca Alkaloid

Pharmacology

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.

Distribution

Rapidly removed from bloodstream and tightly bound to tissues; penetrates blood-brain barrier poorly

Metabolism

Extensively hepatic, via CYP3A4

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 (Crom 1994)

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)

Half-Life Elimination

Terminal: 85 hours (range: 19 to 155 hours)

Use: Labeled Indications

Acute lymphocytic leukemia: Treatment of acute lymphocytic leukemia (ALL)

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

Off Label Uses

Central nervous system tumors (anaplastic oligodendrogliomas/oligoastrocytomas, low-grade gliomas, medulloblastoma, recurrent glioblastoma)

Data from a large prospective randomized phase III trial supports the use of vincristine (in combination with procarbazine and lomustine [PCV regimen]) following radiation therapy for the treatment of low-grade gliomas (eg, supratentorial grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma) [Buckner 2016], [Shaw 2012]. Data (including long-term follow-up) from a multicenter, randomized, controlled phase III trial (EORTC 26951) in patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas support the use of vincristine (as part of the PCV regimen) after radiotherapy for the treatment of this condition [van den Bent 2006], [van den Bent 2013]. Results from another clinical trial (RTOG 9402) demonstrated that early treatment with the PCV regimen followed by radiotherapy significantly improved progression-free survival compared to radiotherapy alone, although the difference in overall survival was not significant [Cairncross 2006]. However, long-term RTOG 9402 results illustrated that in a subset of patients with 1p/19q codeleted tumors, overall survival was significantly longer in patients who received PCV followed by radiotherapy compared to those who received radiotherapy alone [Cairncross 2013]. Data from phase III studies in patients with recurrent glioblastoma support the use of the PCV regimen in these patients [Brada 2010], [Levin 2000].

Data from a large phase III trial in patients with newly-diagnosed average risk medulloblastoma in pediatric and adult patients ages 3 to 21 years support the use of vincristine (in combination with radiation, cisplatin, and either lomustine or cyclophosphamide) for the treatment of nondisseminated medulloblastoma [Packer 2006]. Data from a small study support the use of vincristine (in combination with cisplatin, etoposide, cyclophosphamide, methotrexate, and leucovorin) for the treatment of newly-diagnosed high-risk medulloblastoma [Chi 2004].

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with Richter transformation

Data from studies in patients with Richter transformation or fludarabine-refractory CLL and in patients with Burkitt-type lymphoma (non-Hodgkin lymphoma) supports the use of vincristine (in combination with cyclophosphamide, mesna, doxorubicin, dexamethasone, methotrexate, leucovorin, and cytarabine; HyperCVAD regimen, ± rituximab) in the management of this condition [Thomas 2006], [Tsimberidou 2003]. A large retrospective analysis also supports the use of vincristine (in combination with cyclophosphamide, doxorubicin, and prednisone; CHOP regimen, ± rituximab) for the treatment of CLL/SLL which has undergone Richter transformation [Tsimberidou 2006].

Ewing sarcoma

Data from a randomized controlled trial evaluating the use of vincristine (in combination with doxorubicin, cyclophosphamide, and dactinomycin) in patients with Ewing sarcoma and primitive neuroectodermal tumor of the bone supports the use of vincristine (VAC/IE regimen) for this condition [Grier 2003].

Gestational trophoblastic tumors (high-risk)

Data from studies evaluating the use of vincristine (in combination with etoposide, methotrexate, leucovorin, dactinomycin, and cyclophosphamide [EMA/CO regimen]) in patients with high-risk gestational trophoblastic neoplasia support the use of vincristine in the treatment of this condition [Escobar 2003], [Lurain 2006].

Merkel cell carcinoma (advanced or recurrent)

Data from a small retrospective study suggest that vincristine (in combination with cyclophosphamide and doxorubicin; CAV regimen) may be of benefit in the treatment of advanced or recurrent Merkel cell carcinoma [Fenig 1997]. Data from another retrospective study also suggest the utility of the CAV regimen in the management of recurrent Merkel cell carcinoma [Tai 2000].

Multiple myeloma

Data from a phase III multicenter randomized trial in patients with newly-diagnosed multiple myeloma supports the use of vincristine (in combination with pegylated liposomal doxorubicin and dexamethasone [DVd regimen] or in combination with conventional doxorubicin and dexamethasone [VAd regimen]) for this condition [Rifkin 2006]. Although vincristine-containing regimens such as VAd have been studied for use in newly-diagnosed multiple myeloma, more contemporary regimens are now typically used as first-line treatment. Vincristine (in combination with doxorubicin and dexamethasone) may be considered in patients with multiple relapsed/refractory disease.

Ovarian germ cell tumors

Data from an evaluation of patients with malignant ovarian germ cell tumors supports the use of vincristine (in combination with dactinomycin and cyclophosphamide) for the treatment of this condition [Slayton 1985].

Pheochromocytoma, malignant

Data from a limited number of patients in a small nonrandomized study suggest that vincristine (in combination with cyclophosphamide and dacarbazine) may be beneficial for the treatment of malignant pheochromocytoma [Huang 2008].

Primary CNS lymphoma

Data from 2 multicenter phase II trials support the use of vincristine (in combination with rituximab, high-dose methotrexate, leucovorin, and procarbazine [R-MPV], followed by radiotherapy and cytarabine, and intrathecal methotrexate, if indicated) for the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) [Morris 2013], [Shah 2007]. Data from a single center study also support the use of R-MPV, followed by consolidation high-dose chemotherapy and autologous stem cell transplant in newly-diagnosed PCNSL [Omuro 2015].

Small cell lung cancer (recurrent)

Data from a multicenter, randomized study evaluating the use of vincristine (in combination with cyclophosphamide and doxorubicin [CAV regimen]) support the use of vincristine for the treatment of recurrent small cell lung cancer [von Pawel 1999].

Thymoma, advanced

Data from a limited number of patients suggest that vincristine (in combination with doxorubicin, cisplatin, and cyclophosphamide [ADOC regimen]) may be beneficial for the treatment of advanced thymoma [Fornasiero 1991].

Contraindications

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.

Dosing: Adult

Note: Doses may be capped at a maximum of 2 mg/dose. Dosing and frequency may vary by protocol and/or treatment phase. The World Health Organization (WHO) and the Institute for Safe Medication Practices (ISMP) strongly recommend dispensing vincristine in a minibag (NOT a syringe).

Acute lymphocytic leukemia (ALL): IV:

CALGB 10403 regimen: Patients <40 years of age: 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: 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: 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: 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: 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: 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: 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 ALL:

Kim 2015: 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: 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: 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): IV:

Anaplastic oligodendroglioma/astrocytomas, low-grade gliomas: PCV regimen (in combination with procarbazine, lomustine, and radiation therapy): 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): 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: 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): IV: VDC/IE regimen: VDC: 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): IV: EMA/CO regimen: 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: IV:

BEACOPP (standard or escalated) regimen: 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: 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): IV: CAV regimen: 2 mg on day 1 every 21 days (in combination with cyclophosphamide and doxorubicin) (Fenig 1997).

Multiple myeloma (off-label use): IV:

DVD regimen: 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: 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: IV:

Burkitt lymphoma:

CALGB 10002 regimen (cycles 2 through 7): 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): 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: 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: 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: 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: 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: 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: 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: 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: 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 (PMBCL): DA-EPOCH-R regimen: 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): IV: VAC regimen: 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): IV: R-MPV regimen: Induction: 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: IV:

VAC regimen: Patients <50 years: 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: 1.5 mg/m2 (maximum dose: 2 mg) once weekly per protocol (Raney 2011)

Small cell lung cancer, recurrent (off-label use): IV: CAV regimen: 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): IV: ADOC regimen: 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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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).

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)

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Dose should be capped at a maximum of 2 mg due to neurotoxicity concerns (Griggs 2012).

Reconstitution

Note: The World Health Organization (WHO) and the Institute for Safe Medication Practices (ISMP) strongly recommend dispensing vincristine in a minibag (NOT in a syringe). Vincristine should NOT be prepared during the preparation of any medications intended for CNS administration.

Vincristine may be diluted in NS for IV infusion. Dilution in D5W has also been reported (Beijnen 1989).

Administration

For IV administration only. Fatal if given by other routes.

The World Health Organization (WHO) and the Institute for Safe Medication Practices (ISMP) strongly recommend dispensing vincristine in a minibag (NOT in a syringe). 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).

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 (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 (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).

Storage

Note: Vincristine should be dispensed in a minibag (ISMP 2018). After preparation, keep vincristine in a location away from the separate storage location recommended for medications intended for CNS administration.

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light.

IV solution: According to the manufacturer, solutions diluted in NS and stored at 25°C (77°F) are stable for up to 24 hours when protected from light or 8 hours at normal light conditions. Solutions diluted for infusion in NS or D5W (20 mcg/mL concentration) are reported to be stable for up to 21 days at 4°C (39.2°F) and 25°C (77°F) if protected from light (Beijnen 1989), although the vincristine formulation may have changed since this stability study was conducted. Follow USP 797 recommendations for beyond use dates based on the level of risk for preparation.

Drug Interactions

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

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

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

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

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

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

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

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

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

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fluconazole: May increase the serum concentration of VinCRIStine. Monitor therapy

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

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

Fosphenytoin: May decrease the serum concentration of VinCRIStine. VinCRIStine may decrease the serum concentration of Fosphenytoin. Monitor therapy

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

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

Itraconazole: May enhance the adverse/toxic effect of VinCRIStine. Itraconazole may increase the serum concentration of VinCRIStine. Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

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

Lopinavir: May increase the serum concentration of VinCRIStine. Management: Monitor closely for signs and symptoms of vincristine toxicity; consider temporary interruption of lopinavir/ritonavir antiviral therapy if patients develop significant toxicity with concurrent use. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Macrolide Antibiotics: May increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Macrolides may also increase the distribution of Vinca Alkaloids into certain cells and/or tissues. Management: Consider an alternative to using a macrolide antibiotic when possible in order to avoid the potential for increased vinca alkaloid toxicity. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

MitoMYcin (Systemic): Antineoplastic Agents (Vinca Alkaloids) may enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

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

NIFEdipine: May increase the serum concentration of VinCRIStine. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

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

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

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

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phenytoin: May decrease the serum concentration of VinCRIStine. VinCRIStine may decrease the serum concentration of Phenytoin. Management: . Monitor therapy

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

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

Posaconazole: May enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Posaconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Management: Avoid the concomitant use of posaconazole and vinca alkaloids when possible. If combined, monitor for increased vinca alkaloid toxicities (eg, neurotoxicity, gastrointestinal toxicity). Consider therapy modification

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Ritonavir: May increase the serum concentration of VinCRIStine. Management: Monitor closely for signs and symptoms of vincristine toxicity; consider temporary interruption of ritonavir antiviral therapy if patients develop significant toxicity with concurrent use. Consider therapy modification

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

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

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

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

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Teniposide: May enhance the neurotoxic effect of VinCRIStine. Monitor therapy

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Voriconazole: May enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Voriconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Consider therapy modification

Adverse Reactions

Frequency not defined.

Cardiovascular: Edema, hypertension, hypotension, ischemic heart disease, myocardial infarction, phlebitis

Central nervous system: Abnormal gait, ataxia, coma, cranial nerve dysfunction (auditory impairment, extraocular muscle impairment, laryngeal muscle impairment, motor dysfunction, paralysis, paresis, vestibular damage, vocal cord paralysis), decreased deep tendon reflex, dizziness, headache, neuralgia (common), neurotoxicity (dose-related), paralysis, paresthesia, parotid pain, peripheral neuropathy (common), seizure, sensorimotor neuropathy, sensory disturbance, vertigo

Dermatologic: Alopecia (common), skin rash

Endocrine & metabolic: Hyperuricemia, uric acid nephropathy (acute), weight loss

Gastrointestinal: Abdominal cramps, abdominal pain, anorexia, constipation (common), diarrhea, intestinal necrosis, intestinal perforation, nausea, oral mucosa ulcer, paralytic ileus, sore throat, vomiting

Genitourinary: Bladder dysfunction (atony), dysuria, urinary retention

Hematologic & oncologic: Anemia (mild), hemolytic uremic syndrome, leukopenia (mild), thrombocytopenia (mild), thrombotic thrombocytopenic purpura

Hepatic: Hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease)

Local: Local irritation (if infiltrated)

Neuromuscular & skeletal: Amyotrophy, back pain, foot-drop, jaw pain, limb pain, myalgia, ostealgia

Ophthalmic: Cortical blindness (transient), nystagmus, optic atrophy with blindness

Otic: Deafness

Renal: Polyuria

Respiratory: Bronchospasm, dyspnea

Miscellaneous: Fever, tissue necrosis (if infiltrated)

<1%, postmarketing, and/or case reports: Anaphylaxis, hypersensitivity reaction, SIADH (syndrome of inappropriate antidiuretic hormone secretion)

ALERT: U.S. Boxed Warning

Experienced physician:

Vincristine should be administered by individuals experienced in the administration of vincristine.

Extravasation:

It is extremely important that the intravenous (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:

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.

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation: [US Boxed Warning]: 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. Permanently discontinue vincristine if pulmonary dysfunction occurs.

• 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; dosage modification required. May be associated with hepatic sinusoidal obstruction syndrome (SOS; formerly called veno-occlusive disease [VOD]), increased risk in children <3 years of age; use with caution in hepatobiliary dysfunction. Monitor for signs or symptoms of hepatic SOS, including bilirubin >1.4 mg/dL, unexplained weight gain, ascites, hepatomegaly, or unexplained right upper quadrant pain (Arndt 2004).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special handling:

• Hazardous agent: Avoid eye contamination.

Other warnings/precautions:

• For IV use only: [US Boxed Warning]: For IV administration only; fatal if given by other routes. To prevent administration errors, the Institute for Safe Medication Practices (ISMP) Targeted Medication Safety Best Practices for Hospitals initiative and the World Health Organization strongly recommend dispensing vincristine diluted in a minibag (ISMP 2018; WHO 2007). 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.

Monitoring Parameters

Serum electrolytes (sodium), hepatic function tests, CBC with differential, serum uric acid; monitor infusion site; neurologic examination, monitor for constipation/ileus and for signs/symptoms of peripheral neuropathy

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Vincristine may cause fetal harm if administered during pregnancy. Females of reproductive potential should avoid becoming pregnant during treatment.

Patient Education

What is this drug used for?

• It is used to treat cancer.

Frequently reported side effects of this drug

• Nausea

• Vomiting

• Diarrhea

• Mouth irritation

• Mouth sores

• Lack of appetite

• Abdominal cramps

• Weight loss

• Bone pain

• Joint pain

• Muscle pain

• Back pain

• Hair loss

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection

• Kidney problems like not able to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

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

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

• Abnormal gait

• Shortness of breath

• Burning or numbness feeling

• Muscle weakness

• Severe constipation

• Severe abdominal pain

• Severe loss of strength and energy

• Change in balance

• Not able to move

• Blindness

• Involuntary eye movements

• Throat pain

• Neck pain

• Jaw pain

• Vision changes

• Hearing loss

• Seizures

• Bruising

• Bleeding

• Trouble passing urine

• Painful urination

• Passing a lot of urine

• Severe headache

• Dizziness

• Passing out

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

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

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