Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action VYXEOS (daunorubicin and cytarabine) liposome for injection is a liposomal formulation of daunorubicin and cytarabine at a fixed 1:5 molar ratio. The 1:5 molar ratio of daunorubicin:cytarabine has been shown to have synergistic effects at killing leukemia cells in vitro and in murine models. Daunorubicin has antimitotic and cytotoxic activity, which is achieved by forming complexes with DNA, inhibiting topoisomerase II activity, inhibiting DNA polymerase activity, affecting regulation of gene expression, and producing DNA-damaging free radicals. Cytarabine is a cell cycle phase-specific antineoplastic agent, affecting cells only during the S-phase of cell division. Cytarabine acts primarily through inhibition of DNA polymerase.
Indications
- 1 INDICATIONS AND USAGE VYXEOS is indicated for the treatment of 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. VYXEOS is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor, that is indicated for the treatment of 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. ( 1 )
Common Doses
- 2 DOSAGE AND ADMINISTRATION • Induction: VYXEOS (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome via intravenous infusion over 90 minutes on days 1, 3, and 5 and on days 1 and 3 for subsequent cycles of induction, if needed. ( 2.1 ) • Consolidation: VYXEOS (daunorubicin 29 mg/m 2 and cytarabine 65 mg/m 2 ) liposome via intravenous infusion over 90 minutes on days 1 and 3. ( 2.1 ) • See Full Prescribing Information for instructions on preparation and administration. ( 2.3 , 2.4 ) 2.
Contraindications
- 4 CONTRAINDICATIONS The use of VYXEOS is contraindicated in patients with the following: • History of serious hypersensitivity reaction to cytarabine, daunorubicin, or any component of the formulation [see Warnings and Precautions ( 5.4 )] . • History of serious hypersensitivity to daunorubicin, cytarabine or any component of the formulation. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Hemorrhage [see Warnings and Precautions ( 5.2 )] • Cardiotoxicity [see Warnings and Precautions ( 5.3 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] • Copper Overload [see Warnings and Precautions ( 5.5 )] • Tissue Necrosis [see Warnings and Precautions ( 5.6 )] The most common adverse reactions (incidence ≥ 25%) are hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue,...