Vincristine

IV Incompatibilities

Syringe: furosemide

Y-site: cefepime, furosemide, idarubicin, sodium bicarbonate

IV Compatibilities

Additive: bleomycin, cytarabine, doxorubicin, doxorubicin/ondansetron, fluorouracil, methotrexate

Syringe: bleomycin, cisplatin, cyclophosphamide, doxapram, doxorubicin, droperidol, fluorouracil, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine

Y-site: allopurinol, amifostine, ampho B cholSO4, aztreonam, bleomycin, cisplatin, cladribin, cyclophosphamide, doxorubicin, doxorubicin liposomal, droperidol, etoposide PO4, fligrastim, fludarabine, fluorouracil, gatifloxacin, gemcitabine, granisetron, heparin, leucovorin, linezolid, melphalan, methotrexate, metoclopramide, mitomycin, ondansetron, paclitaxel, piperacillin-tazobactam, sargramostim, teniposide, thiotepa, topotecan, vinbastine, vinorelbine

IV Preparation

IVP: 1 mg/mL (dose/syringe); max syringe size for IVP is a 30 mL syringe & syringe should be <75% full

IVPB: dose/50 mL D5W

IV Administration

Vesicant

IV use ONLY; fatal if given intrathecally

Desired route: IVP administered within 1 min

Has also been administered IVPB over 15 min; central line only for IVPB

Has also been given as slow infusion (4-8 hr) or cont infusion

Extravasation Management

Terminate injection or infusion immediately & aspirate back as much as possible

Apply warm pack for 15-20 min QID & elevate

Storage

Store intact vials under refrigeration at 2-8°C

Since this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

WARNINGS

Caution–This preparation should be administered by individuals experienced in the administration of Vincristine Sulfate Injection, USP. It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration of Vincristine Sulfate Injection, USP may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis.

FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES.

• It is used to treat cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hard stools (constipation).
• Stomach cramps.
• Weight loss.
• Feeling tired or weak.
• Hair loss.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Not hungry.
• Headache.
• Bone, joint, or muscle pain.
• Back pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Vincristine sulfate injection is indicated in acute leukemia.

Vincristine sulfate injection has also been shown to be useful in combination with other oncolytic agents in Hodgkin's disease, non–Hodgkin's malignant lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor.

(vin KRIS teen)

Note: Doses may be capped at a maximum of 2 mg/dose. Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. In order to prevent inadvertent intrathecal administration, the World Health Organization (WHO) and the Institute for Safe Medication Practices (ISMP) strongly recommend dispensing vincristine in a minibag (NOT in a syringe).

Dosing in the manufacturer’s labeling: IV:

Children ≤10 kg: 0.05 mg/kg/dose once weekly

Children >10 kg: 1.5 to 2 mg/m2/dose; frequency may vary based on protocol

Additional dosing in combination therapy; indication-specific and/or off-label dosing:

Acute lymphocytic lymphoma (ALL): IV: Induction phase: 1.5 mg/m2/dose days 0, 7, 14, and 21; Consolidation phase: 1.5 mg/m2/dose days 0, 28, and 56; Delayed intensification phase: 1.5 mg/m2/dose days 0, 7, and 14; Maintenance phase: 1.5 mg/m2/dose days 0, 28, and 56 (Bostrom, 2003) or Induction phase: 1.5 mg/m2/dose days 0, 7, 14, and 21; Consolidation phase: 1.5 mg/m2/dose days 0, 28, and 56; Interim maintenance phases: 1.5 mg/m2/dose days 0 and 28; Delayed intensification phase: 1.5 mg/m2/dose days 0, 7, and 14; Maintenance phase: 1.5 mg/m2/dose every 4 weeks (Avramis, 2002)

Burkitt lymphoma and B-cell ALL: IV: 1.5 mg/m2 (maximum dose: 2 mg) on days 4 and 11 of initial phase cycle (initial phase is in combination with cyclophosphamide, doxorubicin, and CNS prophylaxis; alternates with secondary phase) for a total of 4 cycles of each phase (Bowman, 1996) or 1.5 mg/m2 (maximum dose: 2 mg) 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) (Reiter, 1999)

Ewing's sarcoma (off-label use): IV: 2 mg/m2/dose (maximum dose: 2 mg) on day 1 of a 21-day cycle, administer either every cycle or during odd-numbered cycles (Grier, 2003) or 0.67 mg/m2/day continuous infusion days 1, 2, and 3 (total 2 mg/m2/cycle; maximum dose/cycle: 2 mg) during cycles 1, 2, 3, and 6 (Kolb, 2003)

Hodgkin lymphoma: IV: BEACOPP regimen: 2 mg/m2/dose (maximum dose: 2 mg) on day 7 of a 21-day treatment cycle (Kelly, 2002)

Neuroblastoma: IV:

CE-CAdO regimen: 1.5 mg/m2 (maximum dose: 2 mg) days 1 and 5 every 21 days for 2 cycles (Rubie, 1998) or 0.05 mg/kg days 1 and 5 for 2 cycles (Rubie, 2001)

CAV-P/VP regimen (off-label dosing): 0.033 mg/kg/day continuous infusion days 1, 2, and 3, then 1.5 mg/m2 bolus day 9 of courses 1, 2, 4, and 6 (Kushner, 1994)

Retinoblastoma (off-label use): IV:

Children: 0.05 mg/kg on day 1 every 21 days (in combination with carboplatin) for 8 cycles (Rodriguez-Galindo, 2003)

or

Children ≤36 months: 0.05 mg/kg on day 0 every 28 days (in combination with carboplatin and etoposide) for 6 cycles (Freidman, 2000)

or

Children >36 months: 1.5 mg/m2 (maximum dose: 2 mg) on day 0 every 28 days (in combination with carboplatin and etoposide) for 6 cycles (Friedman, 2000)

Rhabdomyosarcoma: IV:

VA regimen: 1.5 mg/m2/dose (maximum dose: 2 mg) weeks 1-8, weeks 13-20, and weeks 25-32 (Crist, 2001)

VAC regimen: 1.5 mg/m2/dose (maximum dose: 2 mg) weeks 0-12, week 16, weeks 20-25; Continuation therapy: Weeks 29-34, and weeks 38-43 (Crist, 2001)

Wilms' tumor: IV:

Children <1 year: 0.75 mg/m2/dose weekly for 10-11 weeks, then every 3 weeks for 15 additional weeks (total 25-26 weeks) (Pritchard, 1995)

Children ≥1 year: 1.5 mg/m2/dose weekly for 10-11 weeks, then every 3 weeks for 15 additional weeks (total 25-26 weeks) (Pritchard, 1995)

or

Children ≤30 kg: 0.05 mg/kg/dose (maximum dose: 2 mg) weeks 1, 2, 4, 5, 6, 7, 8, 10, and 11, followed by 0.067 mg/kg/dose (maximum dose: 2 mg) weeks 12, 13, 18, and 24 (Green, 2007)

Children >30 kg: 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 (Green, 2007)

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.

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)

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. 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. Avoid combination

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. 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. Monitor therapy

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

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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

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

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. 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

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

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. 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. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

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

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. 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

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. 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. 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. 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. 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 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. 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. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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. 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

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. 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

Frequency not defined.

Cardiovascular: Edema, hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease), 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

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% (Limited to important or life-threatening): Anaphylaxis, hypersensitivity reaction, SIADH (syndrome of inappropriate antidiuretic hormone secretion)