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VinCRIStine (Liposomal)

Medically reviewed by Drugs.com. Last updated on Aug 19, 2020.

Pronunciation

(vin KRIS teen lye po SO mal)

Index Terms

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

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intravenous, as sulfate [preservative free]:

Marqibo: 5 mg/31 mL (1 ea)

Brand Names: U.S.

  • Marqibo

Pharmacologic Category

  • Antineoplastic Agent, Antimicrotubular
  • Antineoplastic Agent, Vinca Alkaloid

Pharmacology

The vincristine liposomal formulation increases the half-life, allowing for enhanced cytotoxic activity in tumor cells. The liposomal formulation of vincristine consists of vincristine encapsulated in sphingosomes, which are composed of sphingomyelin and cholesterol (Bedikian 2006).

Distribution

Vdss: 2.7 L (Bedikian 2006)

Metabolism

Primarily hepatic via CYP3A4.

Excretion

Feces (69%); urine (<8%)

Half-Life Elimination

45 hours (urinary half-life); dependent on rate of vincristine release from sphingosome (Bedikian 2006)

Use: Labeled Indications

Acute lymphoblastic leukemia (relapsed): Treatment of relapsed Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in adults in second or greater relapse or whose disease has progressed after 2 or more antileukemic therapies.

Contraindications

Hypersensitivity to vincristine, liposomal vincristine, or any component of the formulation; patients with Charcot-Marie-Tooth syndrome or other demyelinating conditions; administration via the intrathecal route

Dosing: Adult

Note: Vincristine liposomal and conventional vincristine are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration. The liposomal vincristine dose is based on actual BSA and was not capped in studies (O'Brien 2013; Rodriguez 2009).

Acute lymphoblastic leukemia (relapsed; Philadelphia chromosome-negative): IV: 2.25 mg/m2 once every 7 days (O’Brien 2013).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Demyelinating conditions (including Charcot-Marie-Tooth syndrome): Use is contraindicated.

Fatigue, severe: Consider dose delay, reduction, or therapy discontinuation.

Hematologic toxicity: Grade 3 or 4 neutropenia, thrombocytopenia, or anemia: Consider dose reduction or modification.

Peripheral neuropathy:

Grade 3 (severe symptoms; limiting self-care activities of daily living [ADL]) or persistent grade 2 (moderate symptoms; limiting instrumental ADL) toxicity: Interrupt therapy until recovery to grade 1 or 2, then reduce dose to 2 mg/m2. If grade 3 toxicity persists or if grade 4 toxicity occurs, discontinue liposomal vincristine.

Persistent grade 2 toxicity after first dose reduction to 2 mg/m2: Interrupt therapy for up to 7 days until recovery to grade 1, then reduce dose to 1.825 mg/m2. If neuropathy increases to grade 3 or 4, discontinue liposomal vincristine.

Persistent grade 2 toxicity after second dose reduction to 1.825 mg/m2: Interrupt therapy for up to 7 days until recovery to grade 1, then reduce dose to 1.5 mg/m2. If neuropathy increases to grade 3 or 4, discontinue liposomal vincristine.

Pre-existing neuropathy, severe: Assess treatment benefit versus risk.

Reconstitution

Vincristine liposome preparation requires 60 to 90 minutes of dedicated time utilizing the manufacturer supplied kit. Do not reuse kit components with future doses.

Water bath process:

1). Outside the sterile area, fill a water bath to a depth of at least 8 cm (3.2 inches); water should be heated to and maintained at 63°C to 67°C (145.4°F to 152.6°F) for the entire procedure (use calibrated thermometer to monitor temperature). Maintain water depth of at least 8 cm (3.2 inches) throughout process. Water bath must remain outside the sterile area.

2). In a biological safety cabinet, vent the sodium phosphate vial with a sterile venting needle (with a 0.2 micron filter or other suitable venting device). Venting needle should always be kept above liquid level. Remove 1 mL of sphingomyelin/cholesterol liposome injection and inject into the sodium phosphate vial. Withdraw 5 mL of vincristine sulfate injection and inject into the sodium phosphate vial. Remove the venting needle and gently invert the sodium phosphate vial 5 times to mix (do not shake). Place flotation ring on the sodium phosphate vial.

3). Confirm the water bath is maintained between 63°C to 67°C (145.4°F to 152.6°F). Outside the sterile area, place constituted sodium phosphate vial in the water bath for 10 minutes. Record constitution start and stop time, as well as starting and ending water temperature. After 10 minutes, remove the vial (with tongs), remove flotation ring, then dry the vial, affix vial overlabel, and gently invert 5 times to mix (do not shake).

Block heater process (do NOT use water):

1). Arrange the 3 heater blocks in the block heater; the block holding the constitution vial is centered between the 2 other blank heater blocks (refer to manufacturer labeling for further information). Place a calibrated thermometer in the block opening adjacent to the vial well; thermometer should remain in the block opening through preparation. Turn on block heater and set to 75°C (167°F); verify block temperature (temperature should be 75°C ± 2°C). Equilibrate at this temperature for 15 minutes; maintain block temperature throughout procedure. The flotation ring included in the kit is not required with the block heater process.

2). In a biological safety cabinet, vent the sodium phosphate vial with a sterile venting needle (with a 0.2-micron filter or other suitable venting device). Venting needle should always be kept above liquid level. Remove 1 mL of sphingomyelin/cholesterol liposome injection and inject into the sodium phosphate vial. Withdraw 5 mL of vincristine sulfate injection and inject into the sodium phosphate vial. Remove the venting needle and gently invert the sodium phosphate vial 5 times to mix (do not shake).

3). Confirm the block heater temperature is 73°C to 77°C (163.4°F to 170.6°F). Outside the sterile area, place constituted sodium phosphate vial into the block heater for 18 minutes. Record constitution start and stop time, as well as starting and ending block heater temperature. After 18 minutes, remove the vial (with tongs), affix vial overlabel, and gently invert 5 times to mix (do not shake).

Following water or block heater process: Allow the vial to equilibrate for at least 30 minutes at room temperature (15°C to 30°C [59°F to 86°F]), but for no longer than 12 hours. Once prepared, vincristine sulfate liposome concentration is 5 mg per 31 mL (0.16 mg/mL). Return vial to biologic safety cabinet. Calculate patient's vincristine liposome dose (based on actual BSA); remove corresponding volume from 100 mL NS or D5W infusion bag. Inject vincristine liposome dose into the infusion bag (final volume of 100 mL). Do not use if a precipitate or other foreign matter is present in the vial or infusion bag. The amount contained in each vial may exceed the prescribed dose; use care with dosage and volume calculations. Discard unused portion of the vial. After preparation, keep liposomal vincristine in a location away from the separate storage location recommended for medications intended for CNS administration.

Administration

For IV administration only. Fatal if given by other routes. Liposomal vincristine should NOT be delivered to the patient at the same time as any medications intended for CNS 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 initiation of preparation.

Extravasation of liposomal vincristine may cause tissue injury, although the extent and incidence are not defined; conventional vincristine is a vesicant. Ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, discontinue liposomal vincristine infusion immediately and institute appropriate extravasation management procedures.

Storage

Store intact kit (containing vincristine vial, sphingomyelin/cholesterol liposome vial, and sodium phosphate vial) at 2°C to 8°C (36°F to 46°F); do not freeze. Use appropriate precautions for handling and disposal. Once prepared and diluted in D5W or NS, liposomal vincristine is stable for no more than 12 hours at room temperature; administration should be completed within 12 hours of the initiation of preparation. After preparation, keep liposomal vincristine in a location away from the separate storage location recommended for medications intended for CNS administration.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

CYP3A4 Inducers (Strong): May decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of VinCRIStine (Liposomal). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosphenytoin: May decrease the serum concentration of VinCRIStine (Liposomal). VinCRIStine (Liposomal) may decrease the serum concentration of Fosphenytoin. Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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. 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. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

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

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

NIFEdipine: May increase the serum concentration of VinCRIStine (Liposomal). Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 Inducers: May decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Phenytoin: VinCRIStine (Liposomal) may decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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

Teniposide: May enhance the neurotoxic effect of VinCRIStine (Liposomal). Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

>10%:

Gastrointestinal: Constipation (57%), decreased appetite (33%), diarrhea (37%), nausea (52%)

Hematologic & oncologic: Anemia (34%; grades ≥3: 17%), febrile neutropenia (38%; grades ≥3: 31%), neutropenia (grades ≥3: 18%), thrombocytopenia (grades ≥3: 17%)

Hepatic: Increased serum aspartate aminotransferase (grades ≥3: 6% to 11%)

Nervous system: Fatigue (41%), insomnia (32%), peripheral motor neuropathy (grades ≥3: ≤17%), peripheral neuropathy (39%), peripheral sensory neuropathy (grades ≥3: ≤17%)

Miscellaneous: Fever (43%)

1% to 10%:

Cardiovascular: Hypotension (grades ≥3: 6%), septic shock (grades ≥3: 6%)

Gastrointestinal: Abdominal pain (grades ≥3: 8%), intestinal obstruction (grades ≥3: ≤6%), non-Hirschsprung megacolon (grades ≥3: ≤6%)

Infection: Staphylococcal bacteremia (grades ≥3: 6%)

Nervous system: Mental status changes (grades ≥3: 4%), myasthenia (grades ≥3: 1%), pain (grades ≥3: 8%)

Neuromuscular & skeletal: Asthenia (grades ≥3: 5%)

Respiratory: Pneumonia (grades ≥3: 8%), respiratory distress (grades ≥3: 6%), respiratory failure (grades ≥3: 5%)

Frequency not defined: Hematologic & oncologic: Tumor lysis syndrome

ALERT: U.S. Boxed Warning

For IV use only:

Vincristine (liposomal) is for IV use only and is fatal if given by other routes. Death has occurred with intrathecal administration.

Do not interchange:

Vincristine (liposomal) injection has different dosage recommendations than vincristine injection. Verify drug name and dose prior to preparation and administration to avoid overdosage.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia, thrombocytopenia, and anemia may occur, including grade 3 and greater events. Monitor blood counts prior to each liposomal vincristine dose and as clinically necessary and adjust dose or withhold therapy if necessary. Consider supportive care measures.

• Constipation: Constipation, ileus, bowel obstruction, and colonic pseudo-obstruction have occurred with liposomal vincristine. Patients should be initiated on a prophylactic bowel regimen including a stool softener, dietary fiber, and hydration; additional laxative treatments may be considered.

• Extravasation: Extravasation may occur with liposomal vincristine and causes tissue injury. Avoid extravasation of liposomal vincristine (conventional vincristine is a vesicant). Administer through a secure and free-flowing venous access line. Check for proper needle/catheter placement prior to and during infusion. If extravasation occurs, discontinue liposomal vincristine infusion immediately and institute appropriate extravasation management procedures.

• Fatigue: Severe fatigue was noted in clinical trials; consider treatment delay, dosage adjustment, and/or discontinuation as necessary.

• Hepatotoxicity: Hepatotoxicity (including fatal cases) and increased AST (including grade 3 and higher events) have been reported. Monitor hepatic function tests; reduce dose or interrupt therapy if necessary. Use caution in patients with hepatic impairment; conventional vincristine undergoes extensive hepatic metabolism. Liposomal vincristine has not been studied in patients with severe hepatic impairment. In a study in a limited number of melanoma patients with moderate (Child-Pugh class B) hepatic impairment secondary to liver metastases, Cmax and AUC were comparable to those in patients with normal hepatic function; patients with hepatic impairment received a liposomal vincristine dose of 1 mg/m2 every 2 weeks versus 2 mg/m2 in subjects with normal hepatic function (Bedikian 2011).

• Neurotoxicity: Neuropathies (sensory and motor) are common and cumulative. Monitor for symptoms of neuropathy (peripheral motor and sensory, central, and autonomic), which may include paresthesia, hyper-/hypoesthesia, hyporeflexia or areflexia, neuralgia, jaw pain, decreased vibratory sense, cranial neuropathy, ileus, burning sensation, arthralgia, myalgia, muscle spasm, and/or weakness. Evaluate neurologic status of patients closely prior to liposomal vincristine administration; neurologic toxicity risk is greater when given to patients with preexisting neuromuscular conditions or when used concomitantly with other neurotoxic agents. Administer liposomal vincristine to patients with preexisting neuropathy only after careful risk-benefit assessment. Treatment delay, dosage adjustment, and/or discontinuation may be necessary, based on neurotoxicity severity.

• Tumor lysis syndrome: Tumor lysis syndrome may occur as a consequence of therapy; monitor closely for signs and symptoms and manage accordingly.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Liposomal vs conventional formulation dosing: [US Boxed Warning]: Vincristine liposomal and conventional vincristine are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration to avoid overdoses.

Other warnings/precautions:

• For IV use only: [US Boxed Warning]: For IV administration only. Fatal if given by other routes; inadvertent intrathecal administration has resulted in death. Liposomal vincristine should NOT be prepared during the preparation of any medications intended for CNS administration. After preparation, keep liposomal vincristine in a location away from the separate storage location recommended for medications intended for CNS administration. Liposomal vincristine should NOT be delivered to the patient at the same time with any medications intended for CNS administration.

Monitoring Parameters

CBC with differential and platelets; hepatic function; signs/symptoms of peripheral neuropathy or other neurologic toxicities; sodium (in elderly patients; conventional vincristine may cause or exacerbate hyponatremia or syndrome of inappropriate antidiuretic hormone secretion); evaluate pregnancy status prior to therapy initiation (in females of reproductive potential); signs/symptoms of tumor lysis syndrome; symptoms of constipation; monitor infusion site for extravasation

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for 6 months after the last vincristine (liposomal) dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after the last vincristine (liposomal) dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to vincristine (liposomal) may cause fetal harm.

Patient Education

What is this drug used for?

• It is used to treat a type of leukemia.

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:

• Diarrhea

• Loss of strength and energy

• Lack of appetite

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Tumor lysis syndrome like fast heartbeat or abnormal heartbeat; any passing out; unable to pass urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish

• Burning or numbness feeling

• Change in reflexes

• Jaw pain

• Muscle pain

• Joint pain

• Muscle spasm

• Muscle weakness

• Severe or persistent nerve problems

• Severe constipation

• Severe abdominal pain

• Bloating

• Severe nausea

• Vomiting

• Severe dizziness

• Passing out

• Severe injection site pain, redness, burning, swelling, blisters, sores, or leaking of fluid

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.