Liposomal Daunorubicin and Cytarabine — Drug Monograph

Brand names: Vyxeos

Drug class: Anthracycline

Mechanism of Action

CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1 molar ratio, which has been shown to be synergistic in vitro. The liposomes remain intact in the systemic circulation and preferentially accumulate and persist in the bone marrow. Once within the bone marrow, the liposomes are taken up by leukemia cells through phagocytosis, where they are degraded to release the two drugs intracellularly. Cytarabine acts as an antimetabolite inhibiting DNA polymerase, while daunorubicin acts as an intercalating agent and topoisomerase II inhibitor.

FDA Indications

• For the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC)
• For the treatment of pediatric patients 1 year and older with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC)

Common Side Effects

• Hemorrhage
• Febrile neutropenia
• Rash
• Edema
• Nausea
• Mucositis
• Diarrhea
• Constipation
• Musculoskeletal pain
• Fatigue

Clinical Pearl

Vyxeos is unique because it delivers a fixed molar ratio of cytarabine and daunorubicin that is optimized for synergy, which is maintained in the bone marrow. Unlike conventional 7+3 regimens, Vyxeos induction is given on days 1, 3, and 5, and it has shown superior overall survival in older adults with high-risk AML (t-AML or AML-MRC). Pharmacists must be vigilant to ensure it is not confused with conventional "7+3" doses, as the milligram strengths are not interchangeable.

Related Therapies & Mechanisms

• Daunorubicin (Cerubidine) — Anthracycline · Leukemia
• Doxorubicin (Adriamycin) — Anthracycline · Leukemia
• Idarubicin (Idamycin PFS) — Anthracycline · Leukemia
• Epirubicin (Ellence) — Anthracycline