vincristine liposomal (Rx)

>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%)

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

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