vinCRIStine

Trade Name:

Oncovin® (multiple brands available)

Synonym:

LCR

leurocristine

VCR

Appearance:

clear, colourless solution; may be mixed into larger bags for injection

Monograph Name:

vincristine

Monograph Body:

Drug Monograph

A - Drug Name

vinCRIStine

SYNONYM(S): LCR; leurocristine; VCR

COMMON TRADE NAME(S): Oncovin® (multiple brands available)

B - Mechanism of Action and Pharmacokinetics

The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Vincristine binds reversibly to spindle proteins in S phase. Inhibition of RNA synthesis has also been noted. Vincristine has been shown to arrest cells in metaphase.

Absorption

Not absorbed orally

Distribution

Rapid and extensive reversible tissue binding

Cross blood brain barrier?

Minimal

PPB

75 %

Metabolism

Metabolized in liver by the CYP 3A4 family of P450 isoenzymes

Active metabolites

no information found

Inactive metabolites

no information found

Elimination

Disposition described by a three-compartment model; 30% of the dose is excreted into bile and feces.

Urine

10-20%

Half-life

T ½ α : 5 min

T ½ ß : 2.3 hours

T ½ (gamma) : 85 hours

C - Indications and Status

Health Canada Approvals:

Acute leukemias (acute lymphoblastic leukemia, acute myeloid leukemia)
Breast cancer
Sarcomas (soft tissue, bony tissue, specialized structures)
Hodgkin's disease
Non-Hodgkin's lymphoma
Small cell lung cancer
Cervical Cancer
Colorectal cancer
Wilm's tumour
Melanoma

Other Uses:

Other hematological cancers (chronic lymphocytic leukemia, myeloma)
Gastrointestinal cancers (gastroesophageal, hepatobiliary, pancreatic, neuroendocrine tumours)
Genitourinary cancers (adrenal, prostate)
Gynecological cancers (endometrial, ovarian, GTD)
Thymoma
Brain tumours

D - Adverse Effects

Emetogenic Potential:

Minimal

Extravasation Potential: Vesicant

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Auditory	Hearing impaired (rare)	E
Cardiovascular	Hypertension (rare, autonomic)	E
	Hypotension (rare, autonomic)	E
Dermatological	Alopecia (up to 50%)	E
	Rash (occasional)	I E
Gastrointestinal	Abdominal pain	E
	Anorexia, weight loss	E
	Constipation (neuropathy)	E
	Diarrhea	E
	GI perforation	E
	Mucositis	E
	Nausea, vomiting (mild)	I
Hematological	Myelosuppression (mild)	E
Hypersensitivity	Hypersensitivity (rare)	I
Injection site	Phlebitis (chemical)	I E
Metabolic / Endocrine	SIADH (rare, central neurotoxicity)	E
	Tumor lysis syndrome	I
Musculoskeletal	Musculoskeletal pain (may be severe)	E
Neoplastic	Secondary malignancy (in combination)	D
Nervous System	Autonomic neuropathy (paralytic ileus)	E
	Cranial neuropathy (rare; diplopia, transient blindness, optic atrophy)	E
	Headache	E
	Insomnia (rare)	E
	Peripheral neuropathy (common)	I E D
	Seizure (rare)	I
	Vertigo (rare)	E
Reproductive and breast disorders	Infertility	E
Respiratory	Bronchospasm (acute, rare)	I
Urinary	Urinary retention (autonomic neuropathy; may be severe)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common adverse effects are alopecia and neurotoxicity. Myelosuppression is minimal.

Hyperuricemia during periods of active cell lysis can be minimized with allopurinol and hydration. However, fluid restriction may be required for a patient showing signs of SIADH. In hospitalized patients the urine may be alkalinized, by addition of sodium bicarbonate to the IV fluids.

The tissue necrosis that happens with extravasation may happen days to weeks after the treatment. Patents must be observed for delayed reactions and prior injection sites carefully inspected.

Neurotoxicity with the vinca alkaloids is dose-limiting, qualitatively similar but quantitatively different (vincristine >vinblastine>vinorelbine). It is dose- and exposure-related, with increased toxicity in prolonged infusion. Previous neurotoxicity or neurological disorders may result in decreased tolerance and increased sensitivity. Neurotoxicity is generally reversible, but recovery may be slow.

The most frequent manifestation of nervous system toxicity is peripheral neuropathy; the earliest indication of which is the depression of the Achilles reflex. Later loss of other deep tendon reflexes occurs and is accompanied by peripheral paresthesias, pain and tingling. If therapy is prolonged or high doses are administered, wrist and foot drop, ataxia, a slapping gait and difficulty in walking may occur. Young children may refuse to walk due to extremity pain.

Cranial nerve neuropathy may lead to vocal cord paresis or paralysis (hoarseness, weak voice), ocular motor nerve dysfunction (ptosis, strabismus), bilateral facial nerve palsies, or jaw pain. Severe jaw pain can occur within a few hours of the first dose of vincristine. Cranial nerve toxicities tend to be bilateral and reversible when treatment with vincristine is discontinued.

Autonomic neuropathy is manifested as constipation (which can be severe), abdominal pain, urinary retention and paralytic ileus. Laxatives or stool softeners should be given routinely to prevent constipation. These symptoms resolve with time and may not occur with subsequent treatment. Urinary retention may occur in older patients with obstructive uropathy. If bladder atony occurs, vincristine should be held until symptoms resolve.

E - Dosing

Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. SPECIAL LABELLING IS REQUIRED. (see Administration Guidelines)

Adults:

Intravenous: 1.4 mg/m²weekly
Intravenous: 1 to 1.4 mg/m² q2-3 weeks (maximum dose of 2 mg used in some regimens)

Dose capping
Due to concerns of neurotoxicity, the ASCO guideline recommends vincristine to be capped at a maximum dose of 2 mg when used as part of the CHOP and CVP regimens. It would be prudent to question any dose of vincristine >3 mg or more frequent administration than once a week.

Dosage with Toxicity:

Toxicity / Worst counts in cycle	Action*
Febrile neutropenia, thrombocytopenic bleeding or grade 4 ANC ≥ 7 days	Hold; No dose adjustment required
Neurotoxicity Areflexia only Abnormal buttoning, writing Moderate motor neuropathy (± cranial) Severe motor neuropathy	100% 67% Hold until recovery then reduce dose by 50% Omit
Respiratory symptoms (e.g. bronchospasm, pneumonitis)	Discontinue
Grade 3 other related non-hematological/organ toxicity	Hold
Grade 4 other related non-hematological/organ toxicity	Discontinue
_{*Do not re-treat unless ANC 1.5 x 10⁹L (or defined by protocol), platelets ≥ 100 x 10⁹L and other toxicities have recovered to ≤ grade 2 or indicated in table above.}

Dosage with Hepatic Impairment:

Bilirubin	% usual dose
> 1 – 2.5 x ULN	50%
> 2.5 x ULN	25%

Dosage with Renal Impairment:

No adjustment required

Dosage in the elderly:

Older patients may have more neurotoxicity.

Children:

Refer to regimen being used. Infants are especially susceptible to neurotoxicity and doses should be based on body weight rather than surface area. Doses may be gradually increased as tolerated. Infants are also more susceptible to ileus, SIADH and hematological toxicities from vincristine.

F - Administration Guidelines

FOR INTRAVENOUS USE ONLY. Vincristine is lethal if given intrathecally. No successful antidotes have been described. Syringes containing this product should be labelled “WARNING – FOR INTRAVENOUS USE ONLY. FATAL if given by other routes.”

Direct IV push not recommended, due to risk of inadvertent intrathecal administration.
For intermittent IV use, may mix in small volume minibag (ie. 50mL NS or D5W for adults).
Infuse IV via gravity. Infusion pumps should not be used peripherally, since they deliver infusions at higher pressures and may continue to infuse when extravasation occurs.
During the infusion, suggest nurse to remain present with the patient to observe the IV site for extravasation.

G - Special Precautions

Other:

Contraindicated in patients with the demyelinating form of Charcot-Marie-Tooth Syndrome, childhood polio or with hypersensitivity to vinca alkaloids. Intrathecal administration is absolutely contraindicated. Vincristine should not be given to patients who are receiving radiation that includes liver portals. Use with caution with other neuromuscular disorders, neurotoxic/ototoxic drugs, in leukopenia, complicating infection, or and in patients with Guillain-Barre Syndrome.

Vincristine is potentially fetotoxic, teratogenic, and potentially carcinogenic. It should not be used in pregnancy. Adequate contraception should be used by both sexes during vincristine treatment and for at least 6 months after the last dose. Breast feeding is not recommended since it is unknown whether vincristine or its metabolites are secreted in milk. Fertility may be affected.

H - Interactions

AGENT	EFFECT	MECHANISM	MANAGEMENT
Asparaginase	↑ neuropathy; disturbances of erythropoiesis	asparaginase may ↓ hepatic clearance of vincristine	give vincristine 12-24 hours before asparaginase
Digoxin, ciprofloxacin	↓ effect of digoxin, ciprofloxacin	↓ absorption	Caution; monitor.
Mitomycin	Acute bronchopasm has reported to occur minutes to hours after administration with vinca alkaloids	Unknown	Caution
nifedipine	↑ half-life of vincristine	possibly decreased excretion of vincristine	Avoid combination; monitor closely if given concurrently
phenytoin	↓ serum concentrations of phenytoin	↓ absorption or increased metabolism	monitor serum levels of phenytoin and adjust dose prn
verapamil	↑ vincristine toxicity	↓ protein binding	Avoid combination; monitor closely if given concurrently
CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc)	↓ vincristine effect	↑ metabolism	Caution
Potent CYP 3A4 inhibitors (erythromycin, INH, itraconazole)	↑ vincristine toxicity, especially neurotoxicity	↓ metabolism	Caution
Ototoxic drugs (e.g. cisplatin, aminoglycosides)	↑ ototoxicity risk	Additive; hearing impairment (8th cranial nerve damage) have been described in patients receiving vinca alkaloids	Use with extreme caution

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
Liver function tests; baseline and regular	At each visit
CBC and electrolytes; baseline and regular
Clinical assessment of neurotoxicity, local toxicity, tumour lysis syndrome	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

K - References

Chemotherapy FAQ: Does ONS have recommendations regarding the administration of vincristine by minibag or IV Push? Oncology Nursing Society. Accessed January 30, 2009.

Eisenberg S. Prevent inadvertent administration of intrathecal vincristine. ONS Connect 2009; (Jan): 22.

Gilbar PJ, Carrington CV. The incidence of extravasation of vinca alkaloids supplied in syringes or mini-bags. J Oncol Pharm Practice 2006; 12: 113-8.

Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. April 2, 2012.

Han JY, Choi BG, Song DH, et al. Vinorelbine-associated myelopathy in a patient who previously received paclitaxel: a case report. Med Oncol. 2001; 18(1): 95-7.

McEvoy GK, editor. AHFS Drug Information 2011. Bethesda: American Society of Health-System Pharmacists, p. 1266-9.

Preventing vincristine administration errors. The Joint Commission, Issue 34, July 14, 2005.

Product Monograph: Vincristine Sulfate Injection. Novopharm Limited. March 16, 2012.

Product Monograph: Vincasar PFS® (Vincristine sulfate), Sicor Pharmaceuticals (US), 2003.

Schulmeister L. Preventing vincristine administration errors: does evidence support minibag infusions? Clinical Journal of Oncology Nursing 2006; 10(2):271-3.

Systemic therapy update: Vincristine prepared in minibag and administered by infusion. British Columbia Cancer Agency (BCCA), December 2007.

Vincristine Monograph. Compendium of Pharmaceuticals and Specialties. Canadian Pharmacists Association, March 2009.

World Health Organization. Information Exchange System: Alert No. 115 (QSM/MC/IEA.115). Geneva, Switzerland: World Health Organization; 18 July 2007.

November 2017 republished to enable search by "cancer type" filter

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

vincristine (patient)

Info Sheet Introduction:

• For treating leukemia, lymphoma, sarcoma, and less often in other cancers, usually in combination with other drugs.

Info Sheet Date: Mardi, janvier 10, 2017 Info Sheet body:

Medication Information Sheet

vinCRIStine (Vin-KRIST-een)

This document provides general information about your medication. It does not replace the advice of your health care professional. Always discuss your therapy with your health care professional and refer to the package insert for more details.

Other Name: Oncovin®

Appearance:

clear, colourless solution; may be mixed into larger bags for injection

What is this medication for?

For treating leukemia, lymphoma, sarcoma, and less often in other cancers, usually in combination with other drugs.

What should I do before I have this medication?

Tell your doctor and pharmacist if you have/had significant medical condition(s), especially if you have / had liver problems, nerve problems (numbness/tingling in your fingers and toes), or any allergies.
People who have cancer or leukemia are at a higher risk of developing other cancers/leukemias (usually some years later) or blood clots. Some cancer medications may increase these risks, especially if used for a prolonged period of time. You should discuss any concerns with your doctor.

How will this medication affect sex, pregnancy and breastfeeding?

Vincristine can harm the unborn baby and should not be used by pregnant women.
If there is ANY chance that you or your partner may become pregnant, you and your partner together must: ►Use 2 effective forms of birth control at the same time while taking this drug. Keep using birth control until 6 months after the last dose (general recommendation). Discuss with your healthcare team.
Tell your doctor right away if you or your partner becomes pregnant.
Do not breastfeed while on vincristine treatment.

Effects on Fertility: Probable

Effects on Fertility: Probable

How is this medication given?

This drug is only given by injection into a vein.

What else do I need to know while on this medication?

Do not eat or drink grapefruit, starfruit, Seville oranges or their juices (or products that contain these) while on this treatment. They may increase side effects.
This medication can interact with other medications and can result in the treatment not working as well or cause severe side effects.
Make sure your health care team knows about all your medications (prescription, over-the-counter, herbals and supplements). Check with your health care team before starting or stopping any of them.

What are the side effects of this medication?

The following side effects are common or severe. You may not have all of the side effects. Other side effects may occur. If you have any unusual or bothersome symptoms, discuss with your doctor.

Side effects and what to do	When to contact doctor?
More Common Side Effects

Hair thinning or loss

Use a gentle soft brush; care should be taken with hair sprays, bleaches, dyes and perms.
Your hair usually grows back after your treatment ends, but the texture or colour may change.

Constipation

Eat a balanced diet with fibres such whole grains, fruit and raw vegetables.
Drink plenty of fluids. Try light exercise regularly.
Speak to your doctor if no bowel movement for 3 or more days.
Also see Constipation Pamphlet.*

Contact your health care team if no improvement or if severe

Nausea and vomiting (usually mild)

Drink clear fluids and avoid large meals. Get fresh air and rest.
Limit spicy, fried foods or foods with a strong smell.
Take anti-nausea drug(s) exactly as directed by your doctor. It is easier to prevent nausea than to treat it.
Contact your doctor if nausea lasts more than 48 hours or vomiting for more than 24 hours.
Also see Nausea & Vomiting pamphlet.*

Contact your health care team if no improvement or if severe

Tingling, numb toes or fingers

May slowly return to normal after treatment ends.
Contact your doctor or nurse if you have trouble doing up buttons, writing, picking up small objects, have pain, or trouble with movement.
Less common effects on the nerves in your head/face, leading to weakness or changes in senses such as hearing -- Contact your doctor if these occur.

Contact your health care team if no improvement or if severe

Side effects and what to do	When to contact doctor?
Less Common Side Effects, but may be Severe

Lung problems
(sudden increased cough, breathing problems, chest pain, coughing blood)

Get emergency medical help right away

Rupture in stomach or intestine wall
(Sudden, severe pain in belly or stomach area)

Get emergency medical help right away

Hearing problems or loss

Contact your health care team as soon as possible (office hours)

Allergic reaction (fever, severe rash, itchiness, swollen face, lip or tongue, chest or throat tightness; may occur during or shortly after the drug is given)

Get emergency medical help right away

Unusual bleeding or bruising

You may have black stools, cough up blood, blood in your urine, purple or red dots on your skin or bleeding that will not stop.

Fever, chills, infection

You have a fever if your temperature taken in your mouth (oral temperature) is:

38.3°C (100.9°F) or higher at any time OR
38.0°C (100.4°F) or higher for at least one hour.

While you are getting chemotherapy treatments:

Keep a digital thermometer at home and take your temperature if you feel hot or unwell (for example, chills).
Avoid taking medications that treat a fever before you take your temperature (for example, Tylenol®, acetaminophen, Advil® or ibuprofen) as they may hide a fever.
Do not eat or drink anything hot or cold right before taking your temperature.
Wash your hands often.
Check with your doctor before getting any vaccines, surgeries or visiting your dentist.

If you have a fever, talk to your health care team or go to the closest emergency room.
See our Neutropenia (Low white blood cell count) pamphlet for more information.

Get emergency medical help right away

Pain, burning, redness, or swelling on skin where drug was injected

Let your healthcare team know right away when this happens, since this drug can harm or irritate tissues if it leaks from the vein during injection.

Low measured salt levels in your blood which may lead to mild confusion or swelling

Get emergency medical help right away

Rapid killing of cancer cells when you start treatment may lead to build up of cell waste products

If mild, this may cause gout, with joint pains, but if severe, may cause fevers, kidney failure, confusion and be life-threatening.
You MUST take the preventive medicines given by your doctor AND
Drink plenty of fluids (6-8 glasses per day) and void (urinate) frequently.

Get emergency medical help right away

For more links on how to manage your symptoms go to https://www.cancercareontario.ca/en/symptom-management.

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

vincristine patient.pdf Info Sheet (French):

vincristine pour le patient.pdf Monograph:

vincristine.pdf Phonetic Spelling:

Vin-KRIST-een

Cancer Type: Central Nervous System Gastrointestinal Gynecologic Gestational Trophoblastic Disease Uterine Sarcoma Hematologic Leukemia - Chronic Lymphocytic (CLL) Lymphoma - Non-Hodgkin's High Grade Lymphoma - Non-Hodgkin's Intermediate Grade Lymphoma - Non-Hodgkin's Low Grade Multiple Myeloma Lung Small Cell Thymoma Sarcoma Ewing's Soft Tissue Wilm's Tumour Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Lundi, novembre 6, 2017 Universal Date: 2017-11-06 00:00:00 AddThis: Title URL: vinCRIStine Drug Display Status: Active Revision Summary:

republished to enable search by "cancer type" filter