• Newly-diagnosed therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes.

Contraindicated in:

• Hypersensitivity to daunorubicin, cytarabine, or any other component of the formulation
• End-stage renal disease
• Bilirubin level >3 mg/dL
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Previous anthracycline therapy, underlying cardiovascular disease, history of radiation to mediastinum, or concomitant use of cardiotoxic drugs (↑ risk of cardiotoxicity)
• Wilson's disease (↑ risk of copper toxicity; contains copper)
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Children <1 yr (safety and effectiveness not established)
• Geri: ↑ risk of bleeding in older adults.

CV: arrhythmias, chest pain, hypertension, hypotension, peripheral edema, CARDIOTOXICITY.

Derm: petechiae, pruritus, rash.

EENT: visual impairment, conjunctivitis, deafness, dry eye, eye edema.

F and E: hyponatremia, hypokalemia.

GI: ↓ appetite, abdominal pain, constipation, diarrhea, hemorrhoids, mucositis, nausea, vomiting, ↑ liver enzymes, dyspepsia, hyperbilirubinemia.

GU: renal impairment, ↓ fertility (males).

Hemat: anemia, hemorrhage, neutropenia, thrombocytopenia.

Local: phlebitis at IV site.

Metab: hypoalbuminemia.

MS: pain.

Neuro: anxiety, delirium, dizziness, fatigue, headache, sleep disorders, hallucinations.

Resp: cough, dyspnea, pleural effusion, RESPIRATORY FAILURE.

Misc: chills, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION.

Drug-Drug:

• Additive myelosuppression with other antineoplastics.
• May ↓ antibody response to live-virus vaccines and ↑ the risk of adverse reactions.
• ↑ risk of cardiotoxicity when used with other cardiotoxic drugs.
• ↑ risk of hepatotoxicity with other hepatotoxic agents.

• Lyophilized cake for injection: daunorubicin 44 mg and cytarabine 100 mg/vial;

This product is NOT interchangeable with other products containing daunorubicin or cytarabine.

• IV (Adults and Children ≥1 yr): First induction cycle: daunorubicin 44 mg/m² and cytarabine 100 mg/m² (liposomal) on Days 1, 3, and 5; if remission not achieved, proceed to second induction cycle 2–5 wk later. Second induction cycle (only for patients failing to achieve remission with first induction cycle): daunorubicin 44 mg/m² and cytarabine 100 mg/m² (liposomal) on Days 1 and 3; First consolidation cycle: daunorubicin 29 mg/m² and cytarabine 65 mg/m² (liposomal) on Days 1 and 3 administered 5–8 wk after the start of the last induction cycle; Second consolidation cycle (only for patients who do not show disease progression or unacceptable toxicity after first consolidation cycle): daunorubicin 29 mg/m² and cytarabine 65 mg/m² (liposomal) on Days 1 and 3 administered 5–8 wk after the start of the first consolidation cycle.

Vyxeos

• Daunorubicin: forms a complex with DNA, which subsequently inhibits DNA and RNA synthesis (cell-cycle phase-nonspecific); cytarabine: inhibits DNA synthesis by inhibiting DNA polymerase (cell-cycle S-phase–specific).

• Improved survival.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: anthracyclines, antimetabolites

Daunorubicin

Absorption: IV administration results in complete bioavailability.

Distribution: Well distributed to tissues. Crosses the placenta.

Metabolism/Excretion: Extensively metabolized by the liver to an active metabolite with antineoplastic activity (daunorubicinol); 9% excreted as unchanged drug and active metabolite in urine.

Half-life: 31.5 hr.

Cytarabine

Absorption: IV administration results in complete availability.

Distribution: Well distributed to tissues. Crosses the placenta.

Metabolism/Excretion: Metabolized mostly by the liver to an inactive metabolite; 71% excreted as unchanged drug and inactive metabolite in urine.

Half-life: 40.4 hr.

(plasma levels)

• Explain purpose of medication to patient. If a planned dose is missed, administer as soon as possible and adjust dosing schedule to maintain treatment interval.
• Inform patients of risk of fatal bleeding. Advise of need for periodic monitoring of blood counts and importance of keeping scheduled appointments for blood work and necessary transfusions. Advise patients to contact a health care professional if new onset fever or symptoms of infection (sore throat, pain on urination, chills) or signs of bruising or bleeding occur.
• Advise patient to notify health care professional immediately if signs and symptoms of HF (peripheral edema, dyspnea, rales/crackles, weight gain, jugular venous distention) or hypersensitivity reactions occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications during therapy.
• Rep: May cause fetal harm. Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding. Advise females of reproductive potential and male patients with a partner of reproductive potential to use effective contraception during and for at least 6 months following last dose and to avoid breast feeding for at least 2 wks following last dose. Inform male patients that fertility may be impaired.

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