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Vincristine (conventional): Drug information

Vincristine (conventional): Drug information
(For additional information see "Vincristine (conventional): Patient drug information" and see "Vincristine (conventional): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Experienced provider:

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

Extravasation:

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:

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.

Brand Names: US
  • Vincasar PFS [DSC]
Pharmacologic Category
  • Antineoplastic Agent, Antimicrotubular;
  • Antineoplastic Agent, Vinca Alkaloid
Dosing: Adult

Note: Dispense vincristine in a minibag or other flexible plastic container (NOT in a syringe) (Ref). 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

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 (Ref).

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 (Ref).

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 (Ref), plus a tyrosine kinase inhibitor (for Philadelphia chromosome-positive disease) (Ref).

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 (Ref).

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 (Ref).

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 (Ref).

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 (Ref).

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

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 (Ref).

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 (Ref) or 1.5 mg/m2 (maximum: 2 mg) on day 1 of a 6-week cycle for up to 6 cycles (Ref).

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) (Ref).

Chronic lymphocytic leukemia/small lymphocytic leukemia, with Richter transformation

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) (Ref) 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]) (Ref).

Ewing sarcoma

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 (Ref).

Gestational trophoblastic tumors, high-risk

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 (Ref).

Hodgkin lymphoma

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 (Ref).

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) (Ref).

Merkel cell carcinoma, advanced or recurrent

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) (Ref).

Multiple myeloma

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) (Ref).

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) (Ref).

Non-Hodgkin lymphomas

Non-Hodgkin lymphomas:

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 (Ref).

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 (Ref) or 1.5 mg/m2 (maximum dose: 2 mg) days 1 and 8 of cycles 1 and 3 (Ref); 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) (Ref).

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]) (Ref).

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) (Ref).

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) (Ref).

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 (Ref).

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) (Ref).

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 (Ref).

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) (Ref).

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 (Ref)

Ovarian cancer

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) (Ref)

Pheochromocytoma, malignant

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) (Ref)

Primary CNS lymphoma

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 (Ref) or autologous stem cell transplant (Ref). Two additional cycles of R-MPV may be administered to patients with partial response after initial induction chemotherapy; refer to protocols for details.

Rhabdomyosarcoma

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) (Ref)

VA regimen: Patients <50 years: IV: 1.5 mg/m2 (maximum dose: 2 mg) once weekly per protocol (Ref)

Small cell lung cancer, recurrent

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) (Ref)

Thymoma, advanced

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) (Ref)

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.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Vincristine pharmacokinetics have not been evaluated in kidney impairment. The following recommendations have been extrapolated from drug characteristics reported in patients with normal kidney function; use with caution.

Altered kidney function: No dosage adjustment likely to be necessary for any degree of kidney dysfunction (10% to 20% excreted in the urine) (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large Vd): No supplemental dose or dosage adjustment likely to be necessary (Ref).

Peritoneal dialysis: Unlikely to be dialyzed (large Vd): No dosage adjustment likely to be necessary (Ref).

CRRT: No dosage adjustment likely to be necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment likely to be necessary (Ref).

Dosing: Hepatic Impairment: Adult

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.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Some protocols cap vincristine doses at a maximum of 2 mg/dose. The practice of limiting vincristine doses to 2 mg may not be supported by existing clinical data (Ref); however, many trials use dose capping specific to the regimen; refer to protocol and/or institutional policy for guidance, taking into account performance status and preexisting (or the potential for) neurotoxic events. 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 (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).

Dosing: Adjustment for Toxicity: Adult

Constipation (including upper colon impaction): May require high enemas and laxatives.

Progressive dyspnea with pulmonary dysfunction: Permanently discontinue vincristine.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Vincristine (conventional): Pediatric drug information")

Note: Doses are almost always capped at a maximum of 2 mg/dose/week (Ref). 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 (Ref). The World Health Organization (WHO) and the Institute for Safe Medication Practices (ISMP) strongly recommend dispensing vincristine in a minibag (NOT in a syringe) (Ref).

Acute lymphocytic leukemia of infancy

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, standard risk and high risk

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

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

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 (Ref).

Hodgkin lymphoma

Hodgkin lymphoma: Limited data available:

AV-PC (low-risk regimen): Children and Adolescents: 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) (Ref).

ABVE-PC (high-risk and intermediate regimens): Children and Adolescents: 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 (Ref).

Bv-AVE-PC (high-risk regimen): Children ≥2 years and Adolescents: IV: 1.4 mg/m2/dose (maximum dose: 2.8 mg/dose) on Day 8 of a 21-day treatment cycle for up to 5 cycles in combination with brentuximab, doxorubicin, etoposide, cyclophosphamide, and prednisone (Ref).

BEACOPP regimen (high-risk regimen): Children and Adolescents: 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 (Ref).

Low-grade glioma, CNS tumor

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

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 (Ref).

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) (Ref).

Neuroblastoma

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 (Ref).

CAdO regimen: IV: 0.05 mg/kg/dose on day 1 and 5 and repeated in 21 days (in combination with cyclophosphamide and doxorubicin) (Ref).

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 (Ref).

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 (Ref).

Non-Hodgkin lymphomas

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 (Ref).

Retinoblastoma

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 (Ref).

Rhabdomyosarcoma

Rhabdomyosarcoma: Limited data available (Ref); 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

Wilms tumor: Limited data available (Ref):

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 adjustment for toxicity: Refer to specific protocols for detail for guidance.

Hodgkin lymphoma, classic; high-risk: Children ≥2 years and Adolescents: IV: When used as part of a Bv-AVE-PC regimen with brentuximab, doxorubicin, etoposide, prednisone, and cyclophosphamide along with filgrastim (Ref). Note: Adjustment to the brentuximab dose may be necessary in some instances; refer to Brentuximab monograph for details.

Vincristine Dosage Adjustment for Peripheral Neuropathy Toxicity in Pediatric Patients (Combination Therapy With Brentuximab)a

a Adcetris prescribing information 2022.

Peripheral neuropathy: Grade 2

Reduce vincristine dose per protocol; if neuropathy improves to ≤ grade 1 by day 8 of next cycle, then resume vincristine at full dose.

Peripheral neuropathy: Grade 3 or 4

Discontinue vincristine.

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

Dosing: Kidney Impairment: Pediatric

There are no pediatric specific recommendations; consult individual protocols; based on experience in adult patients, dosing adjustment may not be necessary.

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions

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

Contraindications

Patients with the demyelinating form of Charcot-Marie-Tooth syndrome.

Warnings/Precautions

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]).

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (vinCRIStine Sulfate Intravenous)

1 mg/mL (per mL): $16.93 - $19.37

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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)

Administration: Adult

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

Dispense vincristine in a minibag or other flexible plastic container (NOT in a syringe) (Ref). 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 (Ref). 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 (Ref). 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 (Ref) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) subcutaneously into the extravasation site (Ref).

Administration: Pediatric

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) (Ref). 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 (Ref); administration via gravity instead of infusion pump has also been utilized (Ref). 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 (Ref). Remaining portion of the vincristine dose should be infused through a separate vein.

Hazardous Drugs Handling Considerations

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).

Use: Labeled Indications

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.

Use: Off-Label: Adult

Chronic lymphocytic leukemia/small lymphocytic lymphoma with Richter transformation; CNS tumors: Anaplastic oligodendrogliomas/oligoastrocytomas, low-grade gliomas, medulloblastoma, recurrent glioblastoma; 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

Medication Safety Issues
Sound-alike/look-alike issues:

VinCRIStine may be confused with vinBLAStine, vinorelbine

VinCRIStine conventional may be confused with vinCRIStine liposomal

Oncovin may be confused with Ancobon

High alert medication:

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.

Administration issues:

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.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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-Phenytoin: VinCRIStine may decrease the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of VinCRIStine. 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

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

Reproductive Considerations

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]).

Pregnancy Considerations

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).

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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)

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Topic 10045 Version 327.0

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