Dosing and uses of Marqibo (vincristine liposomal)
Adult dosage forms and strengths
intravenous injection
- 5mg/31mL (0.16mg/mL) final concentration following constitution
- Supplied as a kit that also contains sphingomyelin/cholesterol liposome injection (73.5mg/29.5mg/vial)
Acute Lymphoblastic Leukemia
Indicated for treating Philadelphia chromosome-negative acute lymphoblastic leukemia in adults with second or greater relapse or whose disease has progressed following 2 or more antileukemia therapies
2.25 mg/m² IV infusion over 1 hr q7days
Dosage modifications
Only treat patients with preexisting severe neuropathy after careful risk-benefit assessment
Drug-related peripheral neuropathy
Grade 3 or persistent Grade 2: Interrupt therapy; discontinue if symptoms remain at Grade 3/4; reduce dose to 2 mg/m² after improvement to Grade 1/2
Persistent Grade 2 following first dose reduction: Interrupt therapy for up to 7 days; discontinue if symptoms worsen to Grade 3/4; reduce dose to 1.825 mg/m² after improvement to Grade 1
Persistent Grade 2 following dose reduction to 1.825 mg/m²: Interrupt therapy for up to 7 days; discontinue if symptoms worsen to Grade 3/4; reduce dose to 1.5 mg/m² after improvement to Grade 1
Pediatric dosage forms and strengths
Safety and effectiveness not established
Marqibo (vincristine liposomal) adverse (side) effects
>10%
Blood and lymphatic system disorders (56.6%)
Infections (39.8%)
General disorders and administration site condition (37.3%)
Neuropathy (32.5%)
Febrile neutropenia (31.3%)
Respiratory thoracic and mediastinal disorders (20.5%)
Investigations (24.1%)
Gastrointestinal disorders (25.3%)
Neutropenia (18.1%)
Peripheral sensory and motor neuropathy (16.7%)
Anemia (16.9%)
Thrombocytopenia (16.9%)
Pyrexia (14.5%)
Fatigue (12%)
Psychiatric disorders (10.8%)
Cardiac disorders (10.8%)
1-10%
Vascular disorders (9.6%)
Abdominal pain (8.4%)
Musculoskeletal and connective tissue disorders (8.4%)
Pain (8.4%)
Pneumonia (8.4)
Increased aspartate aminotransferase (7.2%)
Renal and urinary disorders (7.2%)
Cardiac arrest (6%)
Septic shock (6%)
Hypotension (6%)
Staphylococcal bacteremia (6%)
Ileus, colonic pseudo-obstruction (6%)
Respiratory distress (6%)
Constipation (4.8%)
Asthenia (4.8%)
Respiratory failure (4.8%)
Mental status changes (3.6%)
Muscular weakness (1.2%)
Warnings
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 and lactation)
Pregnancy and 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.
Pharmacology of Marqibo (vincristine liposomal)
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
Administration
IV Preparation
Follow proper procedures for handling and disposal of chemotherapy
Preparation takes 60-90 minutes; preparer must have uninterrupted time due to the extensive monitoring of temperature and time required
Observe aseptic technique strictly due to lack of preservative or bacteriostatic agents; prepare in a biological safety cabinet
Do not use with in-line filters
Do not mix with other drugs
Mixing procedure
- Fill water bath with water to a level of at least 8 cm (3.2 inches) measured from the bottom and maintain this minimum water level throughout the procedure; water bath must remain outside of the sterile area
- Place calibrated thermometer in water bath to monitor water temperature and leave it in the water bath until procedure completed; preheat water bath to 63-67°C; maintain this water temperature until completion of the procedure
- Visually inspect each vial in the kit for particulate matter and discoloration prior to preparation, whenever solution and container permit; do not use if precipitate or foreign matter observed
- Remove all the caps on the vials and swab the vials with sterile alcohol pads
- Vent the sodium phosphate injection vial with a sterile venting needle equipped with a sterile 0.2 micron filter or other suitable venting device in the biological safety cabinet; always position venting needle point well above liquid level before adding sphingomyelin/cholesterol liposome injection and vincristine injection
- Withdraw 1 mL of sphingomyelin/cholesterol liposome Injection and inject this into the sodium phosphate injection vial
- Withdraw 5 mL of vincristine sulfate injection (ie, 5 mg) and inject into the sodium phosphate injection vial
- Remove the venting needle and gently invert the sodium phosphate injection vial 5 times to mix; DO NOT SHAKE
- Fit flotation ring around the neck of the sodium phosphate injection vial 10. Confirm that the water bath temperature is at 63-67°C using the calibrated thermometer; remove the sodium phosphate injection vial containing vincristine, sphingomyelin/cholesterol liposome, and sodium phosphate from the biological safety cabinet and place into the water bath for 10 minutes using the calibrated electronic timer
- Monitor the water bath temperature to ensure it is maintained between 63-67°C
- Immediately after placing the mixture vial into the water bath, record the constitution start time and water temperature on the vincristine liposomal overlabel
- At the end of the 10 minutes, confirm that the water temperature is 63-67°C using the calibrated thermometer; remove the vial from the water bath (use tongs to prevent burns) and remove the flotation ring
- Record the final constitution time and the water temperature on the vincristine liposomal overlabel
Labeling
- Dry the exterior of the constituted vial (ie, vincristine liposomal injection) overlabel, and gently invert 5 times to mix; DO NOT SHAKE
- Permit the constituted vial contents to equilibrate for at least 30 minutes to controlled room temperature (15- 30°C, 59-86°F)
- Final vincristine concentration is 5 mg/31 mL (0.16 mg/mL)
- Once vincristine liposomal is prepared, may store at controlled room temperature (15-30°C, 59-86°F) not to exceed 12 hr
- Swab the top of the vial now containing vincristine liposomal with a sterile alcohol pad and return the vial back into the biological safety cabinet
- Calculate the dose based on the patient’s actual body surface area (BSA) and remove the volume corresponding to the dose from an infusion bag containing 100 mL of 5% dextrose injection or 0.9% NaCl injection Inject the vincristine liposomal dose into the infusion bag to result in a final volume of 100 mL
- Complete the information required on the infusion bag label and apply to the infusion bag
- Complete administration of the diluted product within 12 hr of the initiation of vincristine liposomal preparation
- Empty, clean, and dry the water bath after each use
- Deviations in temperature, time, and preparation procedures may fail to ensure proper encapsulation of vincristine sulfate into the liposomes; in the event that the preparation deviates from the instructions in the above steps, the components of the kit should be discarded and a new kit should be used to prepare the dose
IV Administration
Infuse IV over 1 hr
Storage
Kit: Store in refrigerator at 2-8°C; do not freeze
Constituted vial (ie, 5 mg/31 mL prepared vial): May store at controlled room temperature 15-30°C (59-86°F) for up to 12 hr in biological safety hood
