ASH News Daily 2013 - Day 3 - (Page B-34)

Marqibo® (vinCRIStine sulfate LIPOSOME injection) BRIEF SUMMARY Please see the Marqibo package insert for full Prescribing Information. WARNING * For Intravenous Use Only-Fatal if Given by Other Routes. * Death has occurred with intrathecal administration. * Marqibo (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vinCRIStine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage. INDICATIONS AND USAGE Adult ALL in Second or Greater Relapse Marqibo® is indicated for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies. This indication is based on overall response rate. Clinical benefit such as improvement in overall survival has not been verified. DOSAGE AND ADMINISTRATION For Intravenous Use Only. Fatal if Given by Other Routes. Marqibo (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vincristine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage. Recommended Dosage The recommended dose of Marqibo is 2.25 mg/m2 intravenously over 1 hour once every 7 days. Marqibo is liposome-encapsulated vincristine. Dose Modifications: Peripheral Neuropathy Marqibo is contraindicated in patients with demyelinating conditions including Charcot-Marie-Tooth syndrome [see Contraindications]. Patients with preexisting severe neuropathy should be treated with Marqibo only after careful risk-benefit assessment [see Warnings and Precautions]. For dose or schedule modifications guidelines for patients who experience peripheral neuropathy, see Table 1. Table 1. Recommended Dose Modifications for Marqibo-related Peripheral Neuropathy Severity of Peripheral Neuropathy Signs and Symptomsa Modification of Dose and Regimen If the patient develops Grade 3 (severe symptoms; limiting self-care activities of daily living [ADL]b) or persistent Grade 2 (moderate symptoms; limiting instrumental ADLc) peripheral neuropathy: Interrupt Marqibo. If the peripheral neuropathy remains at Grade 3 or 4, discontinue Marqibo. If the peripheral neuropathy recovers to Grade 1 or 2, reduce the Marqibo dose to 2 mg/m2. If the patient has persistent Grade 2 peripheral neuropathy after the first dose reduction to 2 mg/m2: Interrupt Marqibo for up to 7 days. If the peripheral neuropathy increases to Grade 3 or 4, discontinue Marqibo. If the peripheral neuropathy recovers to Grade 1, reduce the Marqibo dose to 1.825 mg/m2. If the patient has persistent Grade 2 peripheral neuropathy after the second dose reduction to 1.825 mg/m2: Interrupt Marqibo for up to 7 days. If the peripheral neuropathy increases to Grade 3 or 4, discontinue Marqibo. If the toxicity recovers to Grade 1, reduce the Marqibo dose to 1.5 mg/m2. a b c Grading based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Self-care ADL: refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Instrumental ADL: refers to preparing meals, shopping for groceries and clothes, using telephone, managing money, etc. Preparation and Handling Items Required by the Pharmacy to Prepare Marqibo * Marqibo Kit * Water batha * Calibrated thermometera (0°C to 100°C) * Calibrated electronic timera * Sterile venting needle or other suitable device equipped with a sterile 0.2 micron filter * 1 mL or 3 mL sterile syringe with needle, and * 5 mL sterile syringe with needle. a The manufacturer will provide the water bath, calibrated thermometer, and calibrated electronic timer to the medical facility at the initial order of Marqibo and will replace them every 2 years. Preparation Instructions for Marqibo (vinCRIStine sulfate LIPOSOME injection), 5 mg/31 mL (0.16 mg/mL) Procedures for handling and disposal of anticancer drugs should be followed [see References]. Call [1 888 292 9617] if you have questions about the preparation of Marqibo. Marqibo takes approximately 60 to 90 minutes to prepare. The preparer should have dedicated uninterrupted time to prepare Marqibo due to the extensive monitoring of temperature and time required for the preparation. Aseptic technique must be strictly observed since no preservative or bacteriostatic agent is present in Marqibo. The preparation steps of Marqibo that involve mixing the Sodium Phosphate Injection, Sphingomyelin/Cholesterol Liposome Injection, and VinCRIStine Sulfate Injection must be done in a biological safety cabinet or by established pharmacy safety procedures for the preparation of sterile injectable formulations and hazardous drugs. However, the preparation steps that involve placement of the vial in the water bath must be done outside of the sterile area. Do not use with in-line filters. Do not mix with other drugs. 1. Fill a 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. The water bath must remain outside of the sterile area. 2. Place a calibrated thermometer in the water bath to monitor water temperature and leave it in the water bath until the procedure has been completed. 3. Preheat water bath to 63°C to 67°C. Maintain this water temperature until completion of the procedure using the calibrated thermometer. 4. Visually inspect each vial in the Marqibo Kit for particulate matter and discoloration prior to preparation, whenever solution and container permit. Do not use if a precipitate or foreign matter is present. 5. Remove all the caps on the vials and swab the vials with sterile alcohol pads. 6. 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 Sulfate Injection. 7. Withdraw 1 mL of Sphingomyelin/Cholesterol Liposome Injection. 8. Inject 1 mL of Sphingomyelin/Cholesterol Liposome Injection into the Sodium Phosphate Injection vial. 9. Withdraw 5 mL of VinCRIStine Sulfate Injection. 10. Inject 5 mL of VinCRIStine Sulfate Injection into the Sodium Phosphate Injection vial. 11. Remove the venting needle and gently invert the Sodium Phosphate Injection vial 5 times to mix. DO NOT SHAKE. 12. Fit Flotation Ring around the neck of the Sodium Phosphate Injection vial. 13. Confirm that the water bath temperature is at 63°C to 67°C using the calibrated thermometer. Remove the Sodium Phosphate Injection vial containing VinCRIStine Sulfate Injection, Sphingomyelin/Cholesterol Liposome Injection, and Sodium Phosphate Injection from the biological safety cabinet and place into the water bath for 10 minutes using the calibrated electronic timer. Monitor the temperature to ensure the temperature is maintained at 63°C to 67°C. 5947_Marqibo_tabloid_ASH_M.indd 2 14. IMMEDIATELY after placing the Sodium Phosphate Injection vial into the water bath, record the constitution start time and water temperature on the Marqibo Overlabel. 15. At the end of the 10 minutes, confirm that the water temperature is 63°C to 67°C using the calibrated thermometer. Remove the vial from the water bath (use tongs to prevent burns) and remove the Flotation Ring. 16. Record the final constitution time and the water temperature on the Marqibo Overlabel. 17. Dry the exterior of the Sodium Phosphate Injection vial with a clean paper towel, affix Marqibo (vinCRIStine sulfate LIPOSOME injection) Overlabel, and gently invert 5 times to mix. DO NOT SHAKE. 18. Permit the constituted vial contents to equilibrate for at least 30 minutes to controlled room temperature (15°C to 30°C, 59°F to 86°F). 19. Marqibo (vinCRIStine sulfate LIPOSOME injection) contains 5 mg/31 mL (0.16 mg/mL) vincristine sulfate. ONCE PREPARED, STORE AT CONTROLLED ROOM TEMPERATURE (15°C to 30°C, 59°F to 86°F) FOR NO MORE THAN 12 HOURS. 20. Swab the top of the vial now containing Marqibo with a sterile alcohol pad and return the vial back into the biological safety cabinet. 21. Calculate the patient's Marqibo dose based on the patient's actual body surface area (BSA) and remove the volume corresponding to the patient's Marqibo dose from an infusion bag containing 100 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection. 22. Inject the dose of Marqibo into the infusion bag to result in a final volume of 100 mL. 23. Complete the information required on the Infusion Bag Label and apply to the infusion bag. 24. Finish administration of the diluted product within 12 hours of the initiation of Marqibo preparation. 25. Empty, clean, and dry the water bath after each use. 26. 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. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if a precipitate or foreign matter is present. CONTRAINDICATIONS Marqibo is contraindicated in patients with demyelinating conditions including Charcot-Marie-Tooth syndrome. Marqibo is contraindicated in patients with hypersensitivity to vincristine sulfate or any of the other components of Marqibo (vinCRIStine sulfate LIPOSOME injection). Marqibo is contraindicated for intrathecal administration. WARNINGS AND PRECAUTIONS For Intravenous Use Only Fatal if Given by Other Routes. Death has occurred with intrathecal use. Extravasation Tissue Injury Only administer through a secure and free-flowing venous access line. If extravasation is suspected, discontinue infusion immediately and consider local treatment measures. Neurologic Toxicity Sensory and motor neuropathies are common and are cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, hyporeflexia, areflexia, neuralgia, jaw pain, decreased vibratory sense, cranial neuropathy, ileus, burning sensation, arthralgia, myalgia, muscle spasm, or weakness, both before and during treatment. Orthostatic hypotension may occur. The risk of neurologic toxicity is greater if Marqibo is administered to patients with preexisting neuromuscular disorders or when other drugs with risk of neurologic toxicity are being given. In the studies of relapsed and/or refractory adult ALL patients, Grade ≥3 neuropathy events occurred in 32.5% of patients. Worsening neuropathy requires dose delay, reduction, or discontinuation of Marqibo [see Dosage and Administration]. Myelosuppression Monitor complete blood counts prior to each dose of Marqibo. If Grade 3 or 4 neutropenia, thrombocytopenia, or anemia develops, consider Marqibo dose modification or reduction as well as supportive care measures. Tumor Lysis Syndrome Tumor lysis syndrome (TLS) may occur in patients with ALL receiving Marqibo. Anticipate, monitor for, and manage. Constipation and Bowel Obstruction Ileus, bowel obstruction, and colonic pseudo-obstruction have occurred. Marqibo can cause constipation [see Adverse Reactions]. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and/or paralytic ileus, considering adequate dietary fiber intake, hydration, and routine use of stool softeners, such as docusate. Additional treatments, such as senna, bisacodyl, milk of magnesia, magnesium citrate, and lactulose may be considered. Fatigue Marqibo can cause severe fatigue. Marqibo dose delay, reduction, or discontinuation may be necessary. Hepatic Toxicity Fatal liver toxicity and elevated levels of aspartate aminotransferase have occurred. Elevated levels of aspartate aminotransferase of Grade ≥3 occurred in 6-11% of patients in clinical trials. Monitor hepatic function tests. Reduce or interrupt Marqibo for hepatic toxicity. Embryofetal Toxicity Marqibo can cause fetal harm when administered to a pregnant woman. Vincristine sulfate liposome injection was teratogenic or caused embryo-fetal death in animals. Women of childbearing potential should avoid becoming pregnant while being treated with Marqibo. There are no adequate and well-controlled studies of Marqibo in pregnant women and there were no reports of pregnancy in any of the clinical studies in the Marqibo clinical development program. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations]. ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the labeling: * For intravenous use only [see Warnings and Precautions] * Extravasation tissue injury [see Warnings and Precautions] * Peripheral Neuropathy [see Warnings and Precautions] * Myelosuppression [see Warnings and Precautions] * Tumor lysis syndrome [see Warnings and Precautions] * Constipation and bowel obstruction [see Warnings and Precautions] * Fatigue [see Warnings and Precautions] * Hepatic toxicity [see Warnings and Precautions] Clinical Trials Safety Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Integrated Summary of Safety in Relapsed and/or Refractory Ph- Adult Acute Lymphoblastic Leukemia Marqibo, at a dose of 2.25 mg/m2 weekly, was studied in a total of 83 patients in two trials: study 1 and study 2. Adverse reactions were observed in 100% of patients. The most common adverse reactions (>30%) were constipation (57%), nausea (52%), pyrexia (43%), fatigue (41%), peripheral neuropathy (39%), febrile neutropenia (38%), diarrhea (37%), anemia (34%), decreased appetite (33%), and insomnia (32%). 10/22/13 4:41 PM 

Table of Contents for the Digital Edition of ASH News Daily 2013 - Day 3

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ASH News Daily 2013 - Day 3

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