Usual Adult Dose for Acute Myeloid Leukemia

• First Induction (Cycle 1): (Cytarabine 100 mg/m2 and daunorubicin 44 mg/m2) liposome IV over 90 minutes on days 1, 3, and 5
• Second Induction (for patients who do not achieve remission with first cycle): (Cytarabine 100 mg/m2 and daunorubicin 44 mg/m2) liposome IV over 90 minutes on days 1 and 3, administered 2 to 5 weeks after the first induction cycle (if there is no unacceptable toxicity with the first induction)
• Consolidation: (Cytarabine 65 mg/m2 and daunorubicin 29 mg/m2) liposome IV over 90 minutes on days 1 and 3; administer the first consolidation cycle 5 to 8 weeks after the start of the last induction; administer the second consolidation cycle 5 to 8 weeks after the start of the first consolidation cycle in patients who do not show disease progression or unacceptable toxicity

Comments:

• Prior to initiating induction, assess cardiac function and obtain liver and renal function studies.
• For patients who do not achieve remission with the first induction cycle, a second induction cycle may be administered 2 to 5 weeks after the first if there was no unacceptable toxicity.

Use: For newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older

Usual Pediatric Dose for Acute Myeloid Leukemia

1 year and older:

• First Induction (Cycle 1): (Cytarabine 100 mg/m2 and daunorubicin 44 mg/m2) liposome IV over 90 minutes on days 1, 3, and 5
• Second Induction (for patients who do not achieve remission with first cycle): (Cytarabine 100 mg/m2 and daunorubicin 44 mg/m2) liposome IV over 90 minutes on days 1 and 3, administered 2 to 5 weeks after the first induction cycle (if there is no unacceptable toxicity with the first induction)
• Consolidation: (Cytarabine 65 mg/m2 and daunorubicin 29 mg/m2) liposome IV over 90 minutes on days 1 and 3; administer the first consolidation cycle 5 to 8 weeks after the start of the last induction; administer the second consolidation cycle 5 to 8 weeks after the start of the first consolidation cycle in patients who do not show disease progression or unacceptable toxicity

Comments:

• Prior to initiating induction, assess cardiac function and obtain liver and renal function studies.
• For patients who do not achieve remission with the first induction cycle, a second induction cycle may be administered 2 to 5 weeks after the first if there was no unacceptable toxicity.

Use: For newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older

Renal Dose Adjustments

• Mild renal impairment (CrCl 60 to 89 mL/min): No adjustment recommended.
• Moderate renal impairment (CrCl 30 to 59 mL/min): No adjustment recommended.
• Severe renal impairment (CrCl 15 to 29 mL/min): No adjustment recommended.
• End-stage renal disease: Data not available

Liver Dose Adjustments

• Bilirubin less than or equal to 3 mg/dL: No adjustment recommended.
• Bilirubin greater than 3 mg/dL: Data not available

Dose Adjustments

Missed Doses:

• If a dose is missed, administer as soon as possible, and adjust the dosing schedule, maintaining the therapy interval.

Hypersensitivity Reactions:
For hypersensitivity reactions of any grade/severity, interrupt the infusion immediately and manage symptoms. Reduce the rate of infusion or discontinue therapy for:

• Mild symptoms: Once symptoms resolve, reinitiate infusion at half the prior rate. Consider premedication with antihistamines and/or corticosteroids for subsequent doses.
• Moderate symptoms: Do not reinitiate infusion. For subsequent doses, premedicate with antihistamines and/or corticosteroids prior to initiating infusion at the same rate.
• Severe or life-threatening symptoms: Permanently discontinue therapy, treat symptoms, and monitor patient until symptoms resolve.

Cardiotoxicity:

• Discontinue therapy in patients who exhibit impaired cardiac function unless benefit outweighs risk.

Precautions

US BOXED WARNINGS:

• This combination drug has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.

CONTRAINDICATIONS:

• Hypersensitivity to either active component or to any of the ingredients

Safety and efficacy have not been established in patients younger than 1 year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For IV use only.
• Administer by continuous IV infusion over 90 minutes via an infusion pump through a central venous catheter or a peripherally inserted central catheter. An in-line membrane filter may be used, provided the minimum pore diameter of the filter is greater than or equal to 15-micron meter.
• Do not mix or administer this drug combination with other drugs.

Storage requirements:

• Store unreconstituted vials in a refrigerator at 2C to 8C (36F to 46F) in an upright position.
• The vial should be stored in its original carton to protect from light.

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

General:

• Administer prophylactic antiemetics before treatment with this combination drug.
• Prior to initiating each cycle, calculate the prior cumulative anthracycline exposure for the patient.
• This drug combination is supplied as a single-dose vial and does not contain any preservatives. Do not save any unused portions for later administration.
• This drug combination is cytotoxic. Follow special handling and disposal procedures.

Monitoring:

• HEMATOLOGIC: Hematologic response and toxicities, blood counts, copper levels
• CARDIOVASCULAR: Cardiac function
• HEPATIC: Hepatic function
• HYPERSENSITIVITY: Hypersensitivity reactions

Patient advice:

• This combination drug can cause fetal harm when administered during pregnancy. Females of reproductive potential should use effective contraception during therapy and for at least 6 months following the last dose.
• Do not breastfeed during therapy and for at least 2 weeks after the last dose.
• According to results in animals, using this medication may impair male fertility.
• This drug combination may cause fatal bleeding.
• Periodic monitoring of blood count is important for blood work and necessary transfusions.
• This drug combination may cause hypersensitivity reactions, including anaphylaxis.
• Contact your healthcare provider in case of new onset fever or symptoms of infection, hypersensitivity reactions, heart failure, or signs of bruising or bleeding.

Frequently asked questions

• How is Vyxeos administered and how long do you take it for?
• Why does Vyxeos have a polymer coating?