Vyxeos (daunorubicin and cytarabine) for acute myeloid leukemia (AML): Dosage, Side Effects & Pregnancy Safety

What is Vyxeos (daunorubicin and cytarabine) and how is it used?

Vyxeos is a chemotherapy treatment given intravenously (IV) to adults with acute myeloid leukemia (AML).

Vyxeos is used to treat the following types of AML patients:

Newly diagnosed, therapy related: those whose AML is related to previously received chemotherapy or radiation therapy (also called therapy-related AML, t-AML) or
Myelodysplasia-related changes: those with AML who previously had certain types of blood disorders, have a specific genetic mutation, or have certain abnormal blood cells (AML with myelodysplasia-related changes, or AML-MRC).

What are the most important side effects and other facts about Vyxeos (daunorubicin and cytarabine)?

WARNING

DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN- AND/OR CYTARABINE-CONTAINING PRODUCTS

Vyxeos 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.

Serious or fatal hemorrhagic events with associated prolonged thrombocytopenia have occurred with Vyxeos. Monitor blood counts regularly until recovery.

Serious side effects of Vyxeos include:

Cardiotoxicity: Vyxeos treatment is not recommended in patients with cardiac function that is less than normal. Discontinue Vyxeos in patients with impaired cardiac function unless the benefit of continuing treatment outweighs the risk.
If severe or life-threatening hypersensitivity reaction occurs, discontinue Vyxeos, treat according to standard of care, and monitor until signs and symptoms resolve.
Daunorubicin has been associated with local tissue necrosis at the site of drug extravasation. Administer Vyxeos with care.
Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.
Copper overload: Reconstituted Vyxeos contains 5 mg/mL copper gluconate, of which 14% is elemental copper. There is no clinical experience with Vyxeos in patients with Wilson’s disease or other copper-related metabolic disorders.

Other side effects of Vyxeos (daunorubicin and cytarabine)

The most common serious side effects (incidence ≥ 5%) of Vyxeos include:

dyspnea,
myocardial toxicity,
sepsis,
pneumonia,
febrile neutropenia,
bacteremia and
hemorrhage.

The adverse reactions leading to discontinuation of Vyxeos include:

prolonged cytopenias,
infection,
cardiotoxicity,
respiratory failure,
hemorrhage (GI and CNS),
renal insufficiency,
colitis, and
generalized medical deterioration.

The most common side effects of Vyxeos (incidence ≥ 25%) include:

hemorrhagic events,
febrile neutropenia,
rash,
edema,
nausea,
mucositis,
diarrhea,
constipation,
musculoskeletal pain,
fatigue,
abdominal pain,
dyspnea,
headache,
cough,
decreased appetite,
arrhythmia,
pneumonia,
bacteremia,
chills,
sleep disorders, and
vomiting.

To report suspected adverse reactions, contact Jazz Pharmaceuticals, Inc. at 1-800-520-5568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

What is the dosage for Vyxeos (daunorubicin and cytarabine)?

A full Vyxeos course consists of 1-2 cycles of Induction and up to 2 cycles of Consolidation at the dose and schedule listed in Table 1.

Prior to initiating each cycle of Vyxeos, calculate the prior cumulative anthracycline exposure for the patient. Administer prophylactic anti-emetics before treatment with Vyxeos.

Table 1: Dose and Schedule for Vyxeos Cycle Vyxeos Dose and Schedule

First
Induction
(daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome days 1, 3, and 5

Second
Induction _{a_{(daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome days 1 and 3}}

Consolidation
(daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) liposome days 1 and 3

a Only for patients failing to achieve a response with the first induction cycle.

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Vyxeos (daunorubicin and cytarabine) contraindications, pregnancy safety and drug interactions

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.

Vyxeos can cause embryo-fetal harm when administered to a pregnant woman.

There are no adequate and well-controlled studies of Vyxeos, daunorubicin, or cytarabine in pregnant women.
There are no data on the presence of daunorubicin, cytarabine, or their metabolites in human milk, their effects on the breastfed infant, or their effects on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with Vyxeos and for at least 2 weeks after the last dose.

Females of reproductive potential should use effective contraception during treatment with Vyxeos and for at least 6 months after the last dose.

Males with female partners of reproductive potential should use effective contraception during treatment with Vyxeos and for at least 6 months after the last dose.

Based on findings of daunorubicin and cytarabine in animals, male fertility may be compromised by treatment with Vyxeos

Safety and effectiveness of Vyxeos in pediatric patients have not been established.

No overall differences in safety were observed between these patients and younger patients, with the exception of bleeding events, which occurred more frequently in patients 65 years and older compared to younger patients (77% vs. 59%).

Drug interactions include:

Cardiotoxic Agents

Concomitant use of cardiotoxic agents may increase the risk of cardiotoxicity. Assess cardiac function more frequently when Vyxeos is coadministered with cardiotoxic agents

Hepatotoxic Agents

Concomitant use with hepatotoxic agents may impair liver function and increase the toxicity of Vyxeos.