Vincristine Sulfate

Class: Antineoplastic Agents
VA Class: AN900
CAS Number: 2068-78-2
Brands: Oncovin

• Administration Warnings


• 
  

  For IV use only.¹³¹

  
  


• 
  

  Fatal if given intrathecally.¹³¹ (See Intrathecal Administration under Cautions.)

  
  


• 
  

  Extremely important to properly place IV needle or catheter before any vincristine is injected.¹³¹

  
  


• 
  

  Leakage into surrounding tissues may cause considerable irritation.¹³¹

  
  


• 
  

  Discontinue immediately if leakage occurs; administer remainder of the dose through another vein.¹³¹

  
  


• 
  

  Local treatment of leakage area (e.g., with hyaluronidase injection, application of moderate heat) may help disperse vincristine and minimize discomfort and possibility of cellulitis.¹³¹

  
  

• Limit to Qualified Personnel


• 
  

  For administration only by individuals experienced in the administration of vincristine.¹³¹

  
  

Introduction

Antineoplastic agent; vinca alkaloid.^{a 135 140}

Uses for Vincristine Sulfate

As a component of many chemotherapeutic regimens because of its relative lack of hematologic toxicity.^{a 136}

Acute Lymphocytic Leukemia

Component of combination chemotherapeutic regimens for the induction of remissions of childhood or adult acute lymphocytic (lymphoblastic) leukemia (ALL).^{136 141 142 143 144 145}

In non-high-risk childhood ALL, combination therapy with vincristine, asparaginase (or pegaspargase), and a corticosteroid (dexamethasone or prednisone) is used as an induction regimen.¹⁴¹ Intensive induction regimens with ≥4 drugs, including vincristine, an anthracycline (e.g., daunorubicin), asparaginase (or pegaspargase), and a corticosteroid, with or without cyclophosphamide, may improve event-free survival but cause greater toxicity.^{136 141 143} Some clinicians reserve 4-drug regimens for patients with high-risk childhood ALL;^{136 141 143} others elect to use such regimens for all patients with childhood ALL regardless of presenting features.¹⁴¹

In adults, induction regimens typically include vincristine, prednisone, and an anthracycline; some regimens also add other drugs (e.g., asparaginase, cyclophosphamide).¹⁴²

Various drugs have been used for combination chemotherapy,^{136 141 142 143 144 145} and comparative efficacy of these regimens is continually being evaluated.^{141 142 143 144 145}

Acute Myeloid Leukemia

In various combination regimens for the treatment of acute myeloid (myelogenous, nonlymphocytic) leukemias (AML, ANLL),¹³⁶ but the comparative efficacy of these combinations is continually being evaluated.^a

Component of second-line regimens for induction in AML.¹³⁶

Hodgkin’s Disease

Component of various chemotherapeutic regimens for Hodgkin’s disease;^{131 136 139} comparative efficacy of various regimens is continually being evaluated.^{137 138 139}

Used in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone (increased-dose BEACOPP regimen) for advanced Hodgkin’s disease.^{136 139}

Being investigated in combination with doxorubicin, bleomycin, vinblastine, mechlorethamine, etoposide, and prednisone (Stanford V regimen) for advanced Hodgkin’s disease.^{136 139}

Non-Hodgkin’s Lymphoma

Component of combination chemotherapeutic regimens as first-line palliative therapy for non-Hodgkin’s lymphomas, including the diffuse histiocytic or lymphocytic type.^{131 136}

Comparative efficacy of various regimens is continually being evaluated, and the best combination or sequence to achieve maximum response has not been established.^a

Neuroblastoma

Component of various regimens as second-line palliative therapy for neuroblastoma.¹³⁶

Rhabdomyosarcoma

Commonly used with dactinomycin, with or without cyclophosphamide, as an adjunct to surgery and/or radiation therapy.^{a 136}

Wilms’ Tumor

In children with Wilms’ tumor, generally used with dactinomycin (with or without doxorubicin or cyclophosphamide),¹³⁶ but the best combination or sequential therapy to achieve maximum response and duration of survival has not been established and comparative efficacy is continually being evaluated.^a

Combination chemotherapy is superior to single-drug therapy as an adjunct to surgery and/or radiation therapy in prolonging relapse-free survival and overall survival.^a

Brain Tumors

Palliative treatment of various primary brain tumors†.¹³⁶

Various first- and second-line regimens that typically include vincristine and lomustine with another antineoplastic agent, such as procarbazine or cisplatin, or a corticosteroid (prednisone) have been used in the treatment of astrocytic tumors (e.g., glioblastoma multiforme and anaplastic astrocytoma),^{136 150 151} medulloblastoma,^{136 152 153} and oligodendroglioma.^{136 154}

AIDS-related Kaposi’s Sarcoma

Used alone^{120 121 146 149} or in combination chemotherapy for the palliative treatment of AIDS-related Kaposi’s sarcoma†.^{136 146 147 148 149 181}

Small Cell Lung Cancer

In combination with cyclophosphamide and doxorubicin (CAV) for the treatment of extensive-stage small cell lung cancer†.^{136 187}

Survival outcomes are similar with CAV or cisplatin/etoposide, and comparative efficacy is continually being evaluated.¹⁸⁷

Current prognosis for small cell lung carcinoma is unsatisfactory regardless of stage; all patients are candidates for inclusion in clinical trials at the time of diagnosis.¹⁸⁷

Other Uses

Used in combination chemotherapy for osteosarcoma (including Ewing's sarcoma), multiple myeloma, and choriocarcinoma†.¹³⁶

Used in combination with cyclophosphamide and prednisone (with or without doxorubicin) for chronic lymphocytic leukemia†.¹³⁶

Used in combination with cisplatin and fluorouracil for hepatoblastoma†.¹³⁶

Used in combination with cyclophosphamide and dacarbazine for pheochromocytoma†.¹³⁶

Has been used for treatment of immune thrombocytopenic purpura†.¹⁹⁷ Used IV with some success for the treatment of thrombotic thrombocytopenic purpura†,^{111 122 123} and the use of vincristine-loaded platelets has reportedly been useful in some cases for the management of autoimmune hemolytic anemia†.¹¹²

Vincristine Sulfate Dosage and Administration

General

• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastics.¹³¹

  
  


• 
  

  Care must be taken to avoid contact with the eyes as severe irritation and possibly corneal ulceration (especially if administered under pressure) can result; if contact occurs, immediately wash eyes with copious amounts of water.¹³¹

  
  


• 
  

  Prophylactic regimen for constipation recommended for all patients receiving the drug.¹³¹

  
  

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer IV only by individuals experienced in the administration of the drug.¹³¹

Very irritating; must not administer IM, sub-Q, or intrathecally.¹³¹ Intrathecal administration almost always results in death.¹³¹ (See Boxed Warning.)

Management of patients mistakenly receiving intrathecal vincristine is a medical emergency.¹³¹ (See Intrathecal Administration under Cautions.)

Administer by IV injection, usually at weekly intervals.¹³¹ Inject appropriate quantity of solution either directly into a large central vein or into tubing of a running IV infusion of 0.9% sodium chloride or 5% dextrose injection.¹³¹

Has been administered as a slow IV infusion†.^{105 108 114 115 116 117}

Extravasation

Extremely important to ensure that needle or catheter is securely within vein to avoid extravasation.¹³¹

If leakage occurs, discontinue injection immediately and administer remainder of dose through another vein; local treatment of the area may minimize discomfort and the possibility of cellulitis.^{131 HID} (See Boxed Warning and also Local Effects under Cautions.)

Dilution

Do not add extra fluid to vial prior to removal of dose or in an attempt to empty vial completely; withdraw solution into accurate dry syringe.¹³¹

It is recommended that vincristine doses be prepared as a diluted solution in a minibag or a 30-mL syringe to prevent inadvertent intrathecal administration of the drug.^{198 199 200}

For adults, dilute the dose in 25 or 50 mL of 0.9% sodium chloride solution in a small-volume IV bag (i.e., minibag);^{198 199} alternatively, the dose may be diluted in 20 mL of 0.9% sodium chloride solution in a 30-mL syringe.¹⁹⁹

For children, dilute the dose in a smaller volume of 0.9% sodium chloride solution in a small-volume IV bag.¹⁹⁸

Rate of Administration

If prepared in a minibag or diluted in a 30 mL syringe, administer by IV injection over 5-10 minutes in adults; in children, administer at a slower rate.¹⁹⁸

If administered undiluted, inject appropriate quantity of solution directly into a vein or into the tubing of a free-flowing infusion over a 1-minute period.^{131 HID}

When diluted in a large volume of IV solution, has been administered as a slow IV infusion† (e.g., over 4–8 hours);^{108 114} continuous 4- or 5-day IV infusions† have also been used.^{105 115 116 117} Consult specialized references for specific information on slow IV infusion.^a

To decrease pressure applied to the veins, experts recommend notusing an IV pump for vesicant drugs such as vincristine when administered by short infusion into a peripheral vein.^{201 202}

Dispensing Precautions

When dispensing, must label syringe or container holding the individual dose with the statement: “Warning: Fatal if given intrathecally. For intravenous use only.”^{131 133}

Enclose container or syringe holding the individual dose in an overwrap (e.g., plastic bag or similar wrap with typed label) bearing the statements: “Do not remove covering until moment of injection. Fatal if given intrathecally. For intravenous use only.”^{131 132 133} (See Intrathecal Administration under Cautions.)

Consider additional measures to prevent inadvertent intrathecal administration, including administering diluted vincristine solutions in minibags; preparing the medication at the time of administration; attaching a unique filter; dispensing separately from all other medications; dispensing directly to the individual who is administering the drug; conducting an independent check of the dose and route of administration for the drug both at the time of preparation and prior to administration; and administering vincristine in a separate room from rooms where intrathecal medications are administered.²⁰⁰

Dosage

Available as vincristine sulfate; dosage expressed in terms of the salt.¹³¹

Consult published protocols for the dosage of vincristine sulfate and other chemotherapeutic agents and the method and sequence of administration.^a

Small daily doses are not recommended because they produce severe toxicity with no added therapeutic benefit.^a

Pediatric Patients

General Dosage

In patients receiving asparaginase concomitantly, administer vincristine 12–24 hours before administration of asparaginase to minimize toxicity.¹³¹ (See Specific Drugs under Interactions.)

Do not administer while patient is receiving radiation therapy through ports that include the liver.¹³¹

IV

Children weighing ≤10 kg: Initially, 0.05 mg/kg at weekly intervals.^{131 a}

Children weighing >10 kg: Usually, 1.5–2 mg/m² at weekly intervals.¹³¹

Determine subsequent doses by clinical and hematologic response and patient tolerance to obtain optimum therapeutic results with minimum adverse effects.^a

Dosage Modification for Toxicity and Contraindications for Continued Therapy

Neurologic Toxicity

Monitor carefully (e.g., history, physical examination) for neurologic toxicity.¹³¹ Dosage reduction may be necessary in preexisting neuromuscular disease or when other agents with neurotoxic potential are used.¹³¹ Some adverse neurologic effects (e.g., neuritic pain, constipation) may lessen or disappear when dosage is reduced.¹³¹

Hematologic Toxicity

Perform CBC before administration of each dose; consider withholding next dose in patients with leukopenia or infectious complications.¹³¹ Leukopenia may lessen or disappear when the dosage of vincristine is reduced.¹³¹

Pulmonary Toxicity

Discontinue vincristine therapy in patients who develop progressive dyspnea.¹³¹

Adults

General Dosage

In patients receiving asparaginase concomitantly, administer vincristine 12–24 hours before administration of asparaginase to minimize toxicity.¹³¹ (See Specific Drugs under Interactions.)

Do not administer while patient is receiving radiation therapy through ports that include the liver.¹³¹

IV

Usually, 1.4 mg/m² at weekly intervals.¹³¹

Determine subsequent doses by clinical and hematologic response and patient tolerance to obtain optimum therapeutic results with minimum adverse effects.^a

Dosage Modification for Toxicity and Contraindications for Continued Therapy

Neurologic Toxicity

Monitor carefully (e.g., history, physical examination) for neurologic toxicity.¹³¹ Dosage reduction may be necessary in preexisting neuromuscular disease or when other agents with neurotoxic potential are used.¹³¹ Some adverse neurologic effects (e.g., neuritic pain, constipation) may lessen or disappear when dosage is reduced.¹³¹

Hematologic Toxicity

Perform CBC before administration of each dose; consider withholding next dose in patients with leukopenia or infectious complications.¹³¹ Leukopenia may lessen or disappear when the dosage of vincristine is reduced.¹³¹

Pulmonary Toxicity

Discontinue vincristine therapy in patients who develop progressive dyspnea.¹³¹

Prescribing Limits

Adults

IV

Maximum 2-mg dose recommended by some clinicians.^a

Special Populations

Hepatic Impairment

IV

In patients with a direct serum bilirubin concentration >3 mg/dL or other evidence of significant hepatic impairment, a 50% dose reduction recommended.¹³¹

Cautions for Vincristine Sulfate

Contraindications

• 
  

  Demyelinating form of Charcot-Marie-Tooth syndrome.¹³¹

  
  

Warnings/Precautions

Warnings

Intrathecal Administration

Fatal if administered intrathecally; management of patients mistakenly receiving intrathecal vincristine is a medical emergency.¹³¹

Prognosis to date generally has been poor despite immediate efforts to remove spinal fluid and flush with lactated Ringer’s injection and other solutions, with such efforts failing to prevent ascending paralysis and death in almost all cases.¹³¹

In one adult patient, progression of paralysis was stopped when treatment was initiated immediately after inadvertent intrathecal injection of vincristine.¹³¹

Treatment consisted of immediate removal of as much CSF as safely possible via lumbar access, followed by flushing of the subarachnoid space with lactated Ringer’s solution infused continuously at a rate of 150 mL/hour through a catheter in a cerebral lateral ventricle and removal of fluid through a lumbar access.¹³¹

As soon as available, fresh frozen plasma (25 mL) diluted in 1 L of lactated Ringer’s solution was infused through the cerebral ventricular catheter at a rate of 75 mL/hour with removal of fluid through the lumbar access.¹³¹ The rate of infusion was adjusted to maintain a CSF protein concentration of 150 mg/dL.¹³¹ Glutamic acid was administered in a dose of 10 g given IV over 24 hours, followed by 500 mg orally 3 times daily for 1 month or until stabilization of neurologic status.^{131 134} The role of glutamic acid in this treatment is uncertain.¹³¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.¹³¹ Avoid pregnancy during therapy.¹³¹ If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.¹³¹

Radiation Therapy

Do not administer while patient is receiving radiation therapy through ports that include the liver.¹³¹

Sensitivity Reactions

Allergic reactions^{126 129 131} (i.e., anaphylaxis,^{126 131} rash,¹³¹ edema¹³¹ ) temporally related to vincristine therapy reported in patients receiving the drug as part of combination chemotherapy regimens.^{126 129 131}

Major Toxicities

Neurotoxicity

Major and dose-limiting adverse effect; severity may vary greatly among patients.^a

Adverse neuromuscular effects often occur in a sequence with early development of sensory impairment and paresthesia followed by neuritic pain and motor difficulties as therapy is continued.¹³¹

Most frequent manifestation is peripheral (mixed sensorimotor) neuropathy; occurs in nearly every patient.^a

Earliest and most consistent peripheral neuropathy indication is asymptomatic depression of the Achilles reflex; loss of other deep tendon reflexes occurs in most patients after ≥3 weekly doses and peripheral paresthesias, especially numbness, pain, and tingling, are common.^a

Wrist drop, foot drop, cranial nerve palsy, atrophy, cramps, ataxia, slapping gait, and difficulty in walking or inability to walk may occur if prolonged or high-dose therapy is given.^a

Cranial nerve palsies may account for headaches and jaw pain; jaw pain usually occurs within 24 hours after the first and/or second dose of vincristine and rarely recurs.^a Pain in other areas (e.g., pharyngeal, parotid gland, bone, back, limb) and myalgia have been reported and may be severe.¹³¹

Cranial nerve palsies and muscular weakness involving the larynx may produce hoarseness and vocal cord paresis, including potentially life-threatening bilateral vocal cord paralysis; those involving extrinsic eye muscles may cause ptosis, double vision, and optic and extraocular neuropathy.^a Optic atrophy with blindness or transient cortical blindness has been reported.¹³¹

Peripheral neuritis (both mononeuritis and polyneuritis) and neuralgia also occur frequently.^a

Autonomic toxicity (e.g., severe constipation or obstipation and abdominal cramps) may occur; ^a adynamic ileus occurs frequently, especially in young children.^a Constipation may take the form of upper-colon impaction; a flat abdominal film may be used to facilitate diagnosis so the physician is not misled by presentation of colicky abdominal pain coupled with an empty rectum.¹³¹ May treat constipation with high enemas and laxatives;¹³¹ a routine prevention regimen (e.g., laxatives, enemas) usually is recommended.¹³¹ Constipation usually persists <7 days with once weekly dose administration;¹³¹ in children, abdominal cramps and adynamic ileus usually also disappear in ≤1 week.^a

Urinary tract disturbances (e.g., bladder atony, incontinence, urinary retention, nocturia, oliguria, dysuria, polyuria) have also been reported.^a Whenever possible, discontinue other drugs causing urinary retention during the first few days after administration of vincristine, particularly in geriatric patients.¹³¹

Other autonomic effects include orthostatic hypotension, abnormal Valsalva response, defective sweating, and myoclonic jerks.^a

CNS effects (e.g., altered consciousness, depression, agitation, insomnia, hallucinations, seizures [often with hypertension], progressive encephalopathy, respiratory difficulties, coma) have occurred.^a Seizures followed by coma have been reported in several pediatric patients.¹³¹

Neurotoxic effects may be additive with those of other neurotoxic agents and spinal cord irradiation.^a Use with caution and monitor dosage and toxicity in patients receiving other neurotoxic drugs or in those with preexisting neuromuscular disease.^a

General Precautions

Highly toxic drug with a low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.^a Administer only under constant supervision of clinicians experienced in therapy with cytotoxic agents.^a

Hyperuricemia

Hyperuricemia may result from extensive purine catabolism accompanying rapid cellular destruction in some patients receiving vincristine, especially those with non-Hodgkin’s lymphomas or leukemia.^a In some patients, uric acid nephropathy may result.¹³¹ Monitor serum uric acid concentrations frequently during first 3–4 weeks of therapy; take appropriate measures to prevent hyperuricemia related to rapid leukemic cell lysis.¹³¹ Minimize hyperuricemic effects by adequate hydration, alkalinization of the urine, and/or administration of allopurinol.^a

Hematologic Effects

Anemia, leukopenia, and thrombocytopenia have been reported.¹³¹ Use caution in presence of leukopenia or complicating infection.¹³¹

Hematologic toxicity produced by vincristine is less than that produced by most other antineoplastic agents.^a

Manufacturers recommend that CBC be performed before each dose.¹³¹

Thrombocytopenia (if present when therapy is initiated) may improve before appearance of bone marrow remission.^a

CNS Leukemia

If CNS leukemia is diagnosed, additional chemotherapy agents may be required; vincristine does not cross blood-brain barrier in adequate amounts.¹³¹

Respiratory Effects

Acute shortness of breath and bronchospasm, which can be severe or life threatening, have occurred; reported most frequently when mitomycin was administered concomitantly.¹³¹

Such reactions may occur a few minutes to several hours after administration of a vinca alkaloid, or up to 2 weeks after mitomycin dose.¹³¹

Progressive dyspnea, which may require chronic therapy, can occur in patients receiving vincristine; do not readminister to these patients.¹³¹

Cardiovascular Effects

Hypertension and hypotension reported.¹³¹ CAD¹³¹ and MI^{124 127 128 130 131} have occurred in patients receiving vincristine in combination with other antineoplastic agents but causal relationship not established;¹³¹ some patients who developed MI had previously received radiation to the mediastinal area, but MI also reported in patients with no history of radiation to mediastinal area or risk factors for CAD.^{124 128 130}

Local Effects

Tissue irritant; may cause phlebitis and necrosis.^a Extravasation can result in pain and cellulitis.^a

Manufacturers state that local injection of hyaluronidase and application of moderate heat may decrease local reactions resulting from extravasation;¹³¹ however, some clinicians prefer to treat extravasation with cold compresses, dilution with 0.9% sodium chloride injection or infiltration of sodium bicarbonate (5 mL of 8.4% injection), and/or local injection of hydrocortisone.^a

Otic Effects

Eighth cranial nerve damage, which may be evident as vestibular manifestations (e.g., dizziness, nystagmus, vertigo) and by auditory manifestations (e.g., varying degrees of hearing impairment including partial or total deafness) that may be temporary or permanent, reported in patients receiving vinca alkaloids.¹³¹

Use vincristine concomitantly with other potentially ototoxic drugs (e.g., platinum-containing antineoplastic agents) with extreme caution.¹³¹ (See Specific Drugs under Interactions.)

Dermatologic Effects

Vincristine-induced alopecia is common; reversible with discontinuance and in some cases, hair may regrow during maintenance therapy.¹³¹

Specific Populations

Pregnancy

Category D.¹³¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether vincristine or its metabolites are distributed into milk. Discontinue nursing or the drug.¹³¹

Hepatic Impairment

Use with caution and reduce dosage in patients with obstructive jaundice or other substantial hepatic impairment.^a (See Hepatic Impairment under Dosage and Administration)

Common Adverse Effects

Asymptomatic depression of the Achilles reflex, loss of deep tendon reflexes, peripheral paresthesias (numbness, pain, and tingling), hair loss, leukopenia, neuritic pain, constipation, sensory loss, wrist drop, foot drop, cranial nerve palsy, atrophy, cramps, ataxia, difficulty walking, inability to walk, slapping gait, muscle wasting, cranial nerve palsies, headache, jaw pain.¹³¹

Interactions for Vincristine Sulfate

Metabolized by CYP microsomal enzymes, including CYP3A.¹³¹

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A: Potential pharmacokinetic interaction (inhibition of vincristine metabolism); use concomitantly with caution.¹³¹

Specific Drugs

Drug	Interaction	Comments
Asparaginase	Possible reduction in hepatic clearance of vincristine131	When used concomitantly, administer vincristine 12–24 hours before administration of asparaginase to minimize toxicity; do not administer asparaginase before vincristine administration131
Itraconazole	Earlier onset and/or increased severity of neuromuscular adverse effects reported with concomitant use, probably related to inhibition of vincristine metabolism131	Use concomitantly with caution131
Mitomycin	Potential increased risk of serious adverse respiratory effects with concomitant use, particularly in preexisting pulmonary dysfunction131	Reactions may occur up to 2 weeks after mitomycin dose131 (see Respiratory Effects under Cautions)
Ototoxic drugs (e.g., platinum-containing antineoplastic agents)	Potential additive ototoxic effect131	Varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage reported in patients receiving vinca alkaloids; use concomitantly with other potentially ototoxic drugs with extreme caution131
Phenytoin	Decreased serum concentrations of phenytoin and increased seizure activity reported with combination chemotherapy regimens that included vincristine, possibly as a result of decreased absorption and/or increased metabolism of phenytoin131	Contribution of vincristine to interaction is uncertain131 Monitor serum phenytoin concentrations and adjust dosage as necessary131

Vincristine Sulfate Pharmacokinetics

Distribution

Extent

Distribution of vincristine and its metabolites not fully characterized; following IV administration, the drug is rapidly and widely distributed.^{100 101 102 103 104}

Following rapid IV injection, rapidly and extensively distributed into bile.¹⁰³

Following rapid IV injection, vincristine and its metabolites (and/or decomposition products) cross the blood-brain barrier poorly, generally do not appear in the CSF in cytotoxic concentrations.¹⁰²

Not known whether vincristine and its metabolites are distributed into milk.^a

Elimination

Metabolism

Not clearly determined; apparently extensively metabolized, probably in the liver by CYP microsomal enzymes, including CYP3A,¹³¹ but extent of metabolism is not clear because vincristine also apparently undergoes decomposition in vivo.^{100 103}

Elimination Route

Vincristine and its metabolites (and/or decomposition products) are excreted principally in feces via biliary elimination (30% within 24 hours and 70% within 72 hours) and to lesser extent in urine (about 10% within 24 hours).^{100 103 104}

Half-life

19–155 hours.¹³¹

Special Populations

In patients with hepatic impairment, metabolism of vincristine may be decreased.^{102 103 131} Only small amounts of vincristine are removed by hemodialysis.¹³¹

Stability

Storage

Parenteral

Injection

2–8°C;¹³¹ protect from light.^a

Doses of 0.5, 1, 2, or 3 mg of vincristine sulfate diluted in 25 or 50 mL of 0.9% sodium chloride injection in small-volume IV bags (i.e., minibags) or in 20 mL of 0.9% sodium chloride injection in a 30-mL syringe remained stable when stored for 7 days at 4°C followed by 2 days at 23°C.¹⁹⁹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Manufacturers state that injection should not be diluted in solutions that alter pH outside range of 3.5–5.5 and do not recommend mixing with solutions other than 0.9% sodium chloride injection or 5% dextrose injection.¹³¹

Solution Compatibility^HID

Compatible
Dextrose 5% in water
Ringer’s injection, lactated
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Bleomycin sulfate
Cytarabine
Doxorubicin HCl
Doxorubicin HCl with etoposide phosphate
Doxorubicin HCl with ondansetron HCl
Fluorouracil
Methotrexate sodium
Variable
Doxorubicin HCl with etoposide

Y-Site CompatibilityHID

Compatible
Allopurinol sodium
Amifostine
Amphotericin B cholesteryl sulfate complex
Aztreonam
Bleomycin sulfate
Cisplatin
Cladribine
Cyclophosphamide
Doxorubicin HCl
Doxorubicin HCl liposome injection
Droperidol
Etoposide phosphate
Filgrastim
Fludarabine phosphate
Fluorouracil
Gemcitabine HCl
Granisetron HCl
Heparin sodium
Leucovorin calcium
Linezolid
Melphalan HCl
Methotrexate sodium
Metoclopramide HCl
Mitomycin
Ondansetron HCl
Oxaliplatin
Paclitaxel
Pemetrexed disodium
Piperacillin sodium–tazobactam sodium
Sargramostim
Teniposide
Thiotepa
Topotecan HCl
Vinblastine sulfate
Vinorelbine tartrate
Incompatible
Cefepime HCl
Furosemide
Idarubicin HCl
Lansoprazole
Sodium bicarbonate

ActionsActions

• 
  

  Mechanism of action not fully elucidated; vincristine and other vinca alkaloids exert cytotoxic effects by binding to tubulin, the protein subunit of the microtubules that form the mitotic spindle.^{135 140}

  
  


• 
  

  Formation of vincristine-tubulin complexes prevents polymerization of the tubulin subunits into microtubules, induces depolymerization of microtubules resulting in inhibition of microtubule assembly and cellular metaphase arrest.¹³⁵

  
  


• 
  

  In high concentrations, also exerts complex effects on nucleic acid and protein synthesis.^a

  
  


• 
  

  Exerts some immunosuppressive activity.^a

  
  

Advice to Patients

• 
  

  Importance of advising patients and/or their parents or guardians of adverse effects and associated manifestations.^a

  
  


• 
  

  Risk of hair loss; reversible when the drug is discontinued.^a Regrowth of hair may occur even when vincristine is continued in therapeutic doses.^a

  
  


• 
  

  Importance of avoiding contact of vincristine with eyes;¹³¹ importance of informing clinician if eye irritation continues after washing affected eye(s) following contact.^a

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^a

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^a

  
  


• 
  

  Importance of informing patients of other important precautionary information.^a (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Vincristine Sulfate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV use only	1 mg/mL (1 and 2 mg)*	Vincristine Sulfate Injection	Hospira

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Bender RA, Castle MC, Margileth DA et al. The pharmacokinetics of [³H]-vincristine in man. Clin Pharmacol Ther. 1977; 22:430-8. [IDIS 95802] [PubMed 902455]

101. Jackson DV Jr, Sethi VS, Spurr CL et al. Pharmcokinetics of vincristine infusion. Cancer Treat Rep. 1981; 65:1043-8. [IDIS 141657] [PubMed 7296550]

102. Jackson DV Jr, Sethi VS, Spurr CL et al. Pharmacokinetics of vincristine in the cerebrospinal fluid of humans. Cancer Res. 1981; 41:1466-8. [IDIS 176921] [PubMed 6260340]

103. Jackson DV Jr, Castle MC, Bender RA. Biliary excretion of vincristine. Clin Pharmacol Ther. 1978; 24:101-7. [PubMed 657711]

104. Owellen RJ, Root MA, Hains FO. Pharmacokinetics of vindesine and vincristine in humans. Cancer Res. 1977; 37:2603-7. [PubMed 872088]

105. Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med. 1984; 310:1353-6. [IDIS 185486] [PubMed 6546971]

106. Ahn YS, Harrington WJ, Seelman RC et al. Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl J Med. 1974; 291:376-80. [IDIS 43910] [PubMed 4847353]

107. Ries CA. Vincristine for treatment of refractory autoimmune thrombocytopenia. N Engl J Med. 1976; 295:1136. [PubMed 980011]

108. Ahn YS, Harrington WJ, Mylvaganam R et al. Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura. Ann Intern Med. 1984; 100:192-6. [IDIS 181312] [PubMed 6537881]

109. Nenci GG, Agnelli G, De Cunto M et al. Infusion of vincristine-loaded platelets in acute ITP refractory to steroids: an alternative to splenectomy. Acta Haematol. 1981; 66:117-21. [PubMed 6794311]

110. Rosse WF. Whatever happened to vinca-loaded platelets? N Engl J Med. 1984; 310:1051-2. Editorial.

111. Gutterman LA, Stevenson TD. Treatment of thrombotic thrombocytopenic purpura with vincristine. JAMA. 1982; 247:1433-6. [IDIS 146911] [PubMed 7199096]

112. Ahn YS, Harrington WJ, Byrnes JJ et al. Treatment of autoimmune hemolytic anemia with vinca-loade