LIPOCYTADAUN(CONS)

_{*Administered 5 to 8 weeks after start of the last induction or 1st consolidation, according to the product monograph. Do not start consolidation until ANC > 0.5 x 10⁹/L and platelets > 50 x 10⁹/L.}

_{**Determine the dose based on the liposomal daunorubicin component. Each 29 mg/m² daunorubicin component delivers cytarabine 65 mg/m².}

For up to 2 cycles unless disease progression or unacceptable toxicity occurs

• Also refer to CCO Antiemetic Recommendations.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Other Supportive Care:

• Consider prophylactic anti-infectives (e.g., anti-bacterials, anti-virals, anti-fungals) for febrile neutropenia prophylaxis.
• Consider prophylaxis for tumour lysis in patients at risk.

Doses should be modified according to the protocol by which the patient is being treated.

Assess cardiac function (e.g., ECG, and MUGA / Echo) prior to starting treatment and monitor routinely.

Calculate total cumulative anthracycline doses (daunorubicin or equivalent) prior to each cycle. Total cumulative daunorubicin doses should not exceed:

• 550mg/m² 
• 400mg/m² in patients with previous thoracic radiation

In the pivotal trial, patients were required to have at baseline, a prior lifetime cumulative anthracycline exposure of < 368 mg/m² daunorubicin (or equivalent).

Management of Infusion-related reactions:

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reaction.

Liposomal daunorubicin / liposomal cytarabine should only be used in severe hepatic impairment if benefits outweigh risks.

No dose adjustment required in patients ≥ 65 years old. Although there were no overall differences in safety between older and younger patients, bleeding events occurred more frequently in patients ≥ 65 years old.

Refer to liposomal DAUNOrubicin / liposomal cytarabine drug monograph(s) for additional details of adverse effects.

Refer to liposomal DAUNOrubicin / liposomal cytarabine drug monograph(s) for additional details.

• Do not administer with other cardiotoxic agents unless cardiac function is closely monitored; avoid anthracycline-based therapy for up to 28 weeks after stopping trastuzumab.
• Monitor liver function more frequently when liposomal daunorubicin / liposomal cytarabine is given with hepatotoxic agents.

Refer to liposomal DAUNOrubicin / liposomal cytarabine drug monograph(s) for additional details.

Administration:

Liposomal daunorubicin / liposomal cytarabine (Vyxeos®) is not interchangeable with other daunorubicin- and/or cytarabine-containing products.
 

• Dose should be determined based on the liposomal daunorubicin component and the individual’s BSA.
• Calculate drug volume based on the concentration of the liposomal daunorubicin component (2.2 mg/mL). 
• Reconstitute each vial with SWFI; mix by careful swirling and gentle inversion. Refer to the product monograph for details.
• Dilute in 500mL NS or D5W; mix by gentle inversion.
• Administer as IV infusion over 90 minutes using an infusion pump through a CVC or PICC line. An in-line membrane filter (minimum pore diameter > 15 µm) may be used.
• Daunorubicin is a vesicant. Exercise care to ensure that there is no extravasation when liposomal daunorubicin / liposomal cytarabine is administered.
• Do NOT administer by intramuscular, intrathecal or subcutaneous route.
• Flush line with NS after administration.
• Do not mix with or administer as an infusion with other medications.
• Store unopened vials in the original carton at 2-8°C. Protect from light. Keep in an upright position.

Contraindications:

• Patients who are hypersensitive to this drug or any of its components
   

Other Warnings/Precautions:

• Liposomal daunorubicin / liposomal cytarabine is not recommended in patients with reduced LVEF.
• Avoid use of live vaccines in patients receiving liposomal daunorubicin / liposomal cytarabine. Inactivated vaccines may be administered; however, response may be diminished.
• Patients should exercise caution when driving or operating heavy machinery as fatigue and dizziness have been reported with liposomal daunorubicin / liposomal cytarabine.
• Caution in patients with Wilson’s disease; the formulation contains copper. A hepatologist and nephrologist should be consulted before starting treatment. Perform serum/urine copper levels and serial neuropsychological assessments at baseline and as clinically indicated.
   

Pregnancy/Lactation:

• This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
• Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
• Fertility effects: Probable

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
 

Recommended Clinical Monitoring

Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 2018;36:2684-2692.

Liposomal DAUNOrubicin / liposomal cytarabine drug monograph. Ontario Health (Cancer Care Ontario).