Vincristine (Liposomal)

Black Box Warnings

For IV use only; other routes may result in fatalities

Death has occurred with intrathecal administration

Do not confuse liposomal injection with vincristine injection due to different dosage recommendations; verify drug name and dose prior to administration

Contraindications

Hypersensitivity

Demyelinating conditions including Charcot-Marie-Tooth syndrome

Intrathecal administration (see Black Box Warnings)

Cautions

IV use only (see Black Box Warnings)

Only administer through secure and free-flowing venous access line; discontinue infusion immediately if extravasation is suspected consider local treatment measures

Sensory and motor neuropathies common and cumulative; monitor for symptoms of neuropathy before and after treatment; risk greater with history of preexisting neuromuscular disorders or concomitant drugs with risk of neurological toxicity

Orthostatic hypotension may occur

Monitor due to risk of myelosuppression; consider dose modification/ reduction if Grade 3/4 neutropenia, thrombocytopenia, or anemia develops

Tumor lysis syndrome

Ileus, bowel obstruction, and colonic pseudo-obstruction; risk of constipation; institute prophylactic bowel regimen

Severe fatigue; dose delay, reduction, or discontinuation may be necessary

Fatal liver toxicity and elevated levels of aspartate aminotransferase; monitor hepatic function tests; reduce or interrupt therapy if necessary

Teratogenic; women of childbearing potential should avoid becoming pregnant while being treated (see Pregnancy & Lactation)

Pregnancy Category: D; fetal malformations (eg, decreased fetal weights, increased early resorptions and post-implantation losses) in animals reported at systemic exposures ~20-40% of those reported in humans at recommended doses; also decreased maternal body weight

Lactation: Unknown if excreted in human milk; use caution, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Spingomyelin/cholesterol liposome-encapsulated formulation of vincristine; binds to tubulin and alters polymerization equilibrium, resulting in altered microtubule structure and function; prevents chromosome segregation and triggers metaphase arrest and inhibition of mitosis

Absorption

Bioavailability: 100%

Peak plasma concentration: 1,220 ng/mL

AUC: 14,566 hr•ng/mL

Metabolism

Metabolized by CYP3A4 isozymes

Elimination

Total body clearance: 347 mL/hr

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

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).
• Upset stomach.
• Feeling tired or weak.
• Loose stools (diarrhea).
• Not hungry.
• Not able to sleep.
• Belly 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.

• If you need to store vincristine at home, talk with your doctor, nurse, or pharmacist about how to store it.

• Liposomal Vincristine
• Liposome Vincristine
• Vincristine Liposomal Sulfate
• Vincristine Liposome
• Vincristine Sulfate Liposome
• VSLI

For IV administration only. FATAL IF GIVEN INTRATHECALLY. Liposomal vincristine should NOT be delivered to the patient at the same time as any medications intended for central nervous system administration.

IV: Infuse over 1 hour. Do not administer IV push or bolus; do not use with in-line filters. Do not administer with other medications. Infusion must be completed within 12 hours of preparation.

Conventional vincristine is a vesicant. Limited information is available regarding liposomal vincristine extravasation, but may cause inflammation if extravasated; avoid extravasation.

Adverse events (fetal malformations, decreased fetal weight, and fetal loss) were observed in animal reproduction studies at doses less than the recommended human dose. Based on the mechanism of action, adverse fetal events would be expected to occur with use in pregnant women. Women of reproductive potential should avoid becoming pregnant during therapy.

Applies to vincristine liposome: intravenous solution, intravenous suspension

Along with its needed effects, vincristine liposome may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking vincristine liposome:

• Abdominal or stomach pain
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• burning, tingling, numbness or pain in the hands, arms, feet, or legs
• change in consciousness
• change in muscle reflexes
• chest pain
• chills
• confusion
• cough
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fever
• increased sensitivity to pain or touch
• low blood pressure or pulse
• lower back or side pain
• nerve pain
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• sensation of pins and needles
• severe constipation
• severe vomiting
• shortness of breath
• sneezing
• sore throat
• stabbing pain
• sweating
• tightness in the chest
• troubled breathing
• ulcers, sores, or white spots in the mouth
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness

• Blue lips, fingernails, or skin
• irregular, fast or slow, or shallow breathing

• Abdominal or stomach tenderness
• clay colored stools
• dark urine
• decreased appetite
• headache
• itching
• joint pain, stiffness, or swelling
• loss of appetite
• nausea and vomiting
• skin rash
• swelling of the feet or lower legs
• yellow eyes or skin

Some side effects of vincristine liposome may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Lack or loss of strength
• mental depression or anxiety
• muscle weakness
• nightmares or unusually vivid dreams

• Redness, pain, or swelling at the injection site