Hospital Pharmacy - June 2020 - 146

VYXEOS® (daunorubicin and cytarabine) liposome for injection,
for intravenous use
BRIEF SUMMARY OF PRESCRIBING INFORMATION: Consult
the Full Prescribing Information, including BOXED Warning,
for complete product information.
Initial U.S. Approval: 2017
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
[see Warnings and Precautions].

INDICATIONS AND USAGE
VYXEOS is indicated for the treatment of adults with newly-diagnosed
therapy-related acute myeloid leukemia (t-AML) or AML with
myelodysplasia-related changes (AML-MRC).
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].
WARNINGS AND PRECAUTIONS
Do Not Interchange With Other Daunorubicin And/Or
Cytarabine-Containing Products
Due to substantial differences in the pharmacokinetic parameters,
the dose and schedule recommendations for VYXEOS are different
from those for 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. Do not substitute other
preparations of daunorubicin or cytarabine for VYXEOS.
Hemorrhage
Serious or fatal hemorrhage events, including fatal central nervous
system (CNS) hemorrhages, associated with prolonged severe
thrombocytopenia, have occurred in patients treated with VYXEOS.
In Study 1 (NCT01696084), the incidence of any grade hemorrhagic
events during the entire treatment period was 74% of patients on the
VYXEOS arm and 56% on the control arm. The most frequently reported
hemorrhagic event was epistaxis (36% in VYXEOS arm and 18% in control
arm). Grade 3 or greater events occurred in 12% of VYXEOS treated
patients and 8% of patients treated with 7+3. Fatal treatment-emergent
CNS hemorrhage not in the setting of progressive disease occurred in
2% of patients on the VYXEOS arm and in 0.7% of patients on the control
arm. Monitor blood counts regularly until recovery and administer
platelet transfusion support as required [see Adverse Reactions].
Cardiotoxicity
VYXEOS contains the anthracycline daunorubicin, which has a known risk
of cardiotoxicity. Prior therapy with anthracyclines, pre-existing cardiac
disease, previous radiotherapy to the mediastinum, or concomitant use of
cardiotoxic drugs may increase the risk of daunorubicin-induced cardiac
toxicity. Prior to administering VYXEOS, obtain an electrocardiogram (ECG)
and assess cardiac function by multi-gated radionuclide angiography
(MUGA) scan or echocardiography (ECHO). Repeat MUGA or ECHO
determinations of left ventricular ejection fraction (LVEF) prior to
consolidation with VYXEOS and as clinically required. Discontinue
VYXEOS in patients with impaired cardiac function unless the benefit of
initiating or continuing treatment outweighs the risk. VYXEOS treatment
is not recommended in patients with LVEF that is less than normal.
Total cumulative doses of non-liposomal daunorubicin greater than
550 mg/m2 have been associated with an increased incidence of
drug-induced congestive heart failure. The tolerable limit appears lower
(400 mg/m2) in patients who received radiation therapy to the mediastinum.

Calculate the lifetime cumulative anthracycline exposure prior to each
cycle of VYXEOS. VYXEOS treatment is not recommended in patients
whose lifetime anthracycline exposure has reached the maximum
cumulative limit. The exposure to daunorubicin following each cycle
of VYXEOS is shown in Table 1.
Table 1: Cumulative Exposure of Daunorubicin per Cycle of VYXEOS
Therapy

Daunorubicin
per Dose

Number
of Doses
per Cycle

Daunorubicin
per Cycle

First Induction
Cycle

44 mg/m2

3

132 mg/m2

Second Induction
Cycle

44 mg/m2

2

88 mg/m2

Each Consolidation
Cycle

29 mg/m2

2

58 mg/m2

Hypersensitivity Reactions
Serious or fatal hypersensitivity reactions, including anaphylactic
reactions, have been reported with daunorubicin and cytarabine.
Monitor patients for hypersensitivity reactions. If a mild or moderate
hypersensitivity reaction occurs, interrupt or slow the rate of infusion
with VYXEOS and manage symptoms. If a severe or life-threatening
hypersensitivity reaction occurs, discontinue VYXEOS permanently,
treat symptoms according to the standard of care, and monitor until
symptoms resolve.
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. The maximum theoretical total exposure of copper under the
recommended VYXEOS dosing regimen is 106 mg/m2. Consult with a
hepatologist and nephrologist with expertise in managing acute copper
toxicity in patients with Wilson's disease treated with VYXEOS. Monitor
total serum copper, serum non-ceruloplasmin bound copper, 24-hour
urine copper levels and serial neuropsychological examinations in
these patients. Use VYXEOS in patients with Wilson's disease only if the
benefits outweigh the risks. Discontinue VYXEOS in patients with signs
or symptoms of acute copper toxicity.
Tissue Necrosis
Daunorubicin has been associated with severe local tissue necrosis at
the site of drug extravasation. Administer VYXEOS by the intravenous
route only. Do not administer by intramuscular or subcutaneous route.
Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal studies
with daunorubicin and cytarabine, 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. Daunorubicin and cytarabine are reproductive and
developmental toxicants in multiple species (mice, rats, and/or dogs),
starting at a dose that was approximately 0.02 times the exposure in
patients at the recommended human dose on an mg/m2 basis. Patients
should be advised to avoid becoming pregnant while taking VYXEOS.
If this drug is used during pregnancy or if the patient becomes pregnant
while taking this drug, apprise the patient of the potential risk to a fetus.
Advise females and males of reproductive potential to use effective
contraception during treatment and for 6 months following the last
dose of VYXEOS [see Use in Specific Populations].
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail
in other sections of the labeling:
* Hemorrhage [see Warnings and Precautions]
* Cardiotoxicity [see Warnings and Precautions]
* Hypersensitivity Reactions [see Warnings and Precautions]
* Copper Overload [see Warnings and Precautions]
* Tissue Necrosis [see Warnings and Precautions]
Hospital Pharmacy - June 2020

Table of Contents for the Digital Edition of Hospital Pharmacy - June 2020
