Hospital Pharmacy - June 2020 - 148

Laboratory Abnormalities
All patients developed severe neutropenia, thrombocytopenia, and anemia.
See Table 3 for the incidences of Grade 3 thrombocytopenia and Grade 4
neutropenia that were prolonged in the absence of active leukemia.
Table 3: Prolonged Cytopenias for Patients in Study 1
Induction 1
VYXEOS
7+3
N=58
N=34
n (%)
n (%)
Prolonged
thrombocytopeniaa
Prolonged
neutropeniaa

Consolidation 1b
VYXEOS
5+2
N=48
N=32
n (%)
n (%)

16 (28)

4 (12)

12 (25)

5 (16)

10 (17)

1 (3)

5 (10)

1 (3)

Platelets <50 Gi/L or neutrophils <0.5 Gi/L lasting past cycle day 42
in the absence of active leukemia.
b
Patients receiving at least 1 consolidation.
a

Grade 3-4 chemistry abnormalities occurring in greater than 5%
of VYXEOS treated patients in Study 1 are presented in Table 4.
Table 4: Grade 3-4a Chemistry Abnormalities ≥5% of VYXEOS
Treated Patients in Study 1
Induction
VYXEOS
7+3
N=153
N=151
n (%)
n (%)
Chemistry Abnormalities
Hyponatremia
21 (14)
20 (13)
Hypokalemia
14 (9)
19 (13)
Hypoalbuminemia
11 (7)
19 (13)
Hyperbilirubinemia
9 (6)
6 (4)
Alanine
7 (5)
8 (5)
aminotransferase

Consolidation
VYXEOS
5+2
N=49
N=32
n (%)
n (%)
3 (6)
3 (6)
1 (2)
1 (2)

0
2 (6)
4 (13)
1 (3)

0

1 (3)

Graded using NCI CTCAE version 3.0.

a

DRUG INTERACTIONS
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 [see Warnings and Precautions].
Hepatotoxic Agents
Concomitant use with hepatotoxic agents may impair liver function
and increase the toxicity of VYXEOS. Monitor hepatic function more
frequently when VYXEOS is coadministered with hepatotoxic agents.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Based on anecdotal data of cytarabine in pregnant women and results
of studies of daunorubicin and cytarabine in animals, 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 a mg/m2 basis [see Animal Data]. 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 harm to a fetus.

The estimated background risk of major birth defects and miscarriage
for the indicated population is unknown. Adverse outcomes in pregnancy
occur regardless of the health of the mother or the use of medications. In
the U.S. general population, the estimated background risks of major birth
defects and miscarriage in clinically recognized pregnancies are 2 to 4%
and 15 to 20%, respectively.
Data
Human Data
Cytarabine can cause fetal harm if a pregnant woman is exposed to
the drug. Four anecdotal cases of major limb malformations have been
reported in infants after their mothers received intravenous cytarabine,
alone or in combination with other agents, during the first trimester.
Animal Data
A liposomal formulation of daunorubicin was administered to rats on
gestation days 6 through 15 at 0.3, 1.0, or 2.0 mg/kg/day (about 0.04, 0.14,
or 0.27 the recommended human dose on a mg/m2 basis) and produced
severe maternal toxicity and embryolethality at 2.0 mg/kg/day and
was embryotoxic and caused fetal malformations (anophthalmia,
microphthalmia, incomplete ossification) at 0.3 mg/kg/day. Embryotoxicity
was characterized by increased embryo-fetal deaths, reduced numbers
of litters, and reduced litter sizes.
Cytarabine was teratogenic in mice (cleft palate, phocomelia, deformed
appendages, skeletal abnormalities) when doses ≥2 mg/kg/day were
administered IP during the period of organogenesis (about 0.06 times
the recommended human dose on a mg/m2 basis), and in rats
(deformed appendages) when 20 mg/kg was administered as a single
IP dose on day 12 of gestation (about 1.2 times the recommended human
dose on a mg/m2 basis). Single IP doses of 50 mg/kg in rats (about
3 times the recommended human dose on a mg/m2 basis) on day 14
of gestation reduced prenatal and postnatal brain size and permanent
impairment of learning ability.
Cytarabine was embryotoxic in mice when administered during the period
of organogenesis. Embryotoxicity was characterized by decreased fetal
weight at 0.5 mg/kg/day (about 0.02 times the recommended human
dose on a mg/m2 basis), and increased early and late resorptions and
decreased live litter sizes at 8 mg/kg/day (about 0.24 times the
recommended human dose on a mg/m2 basis).
Lactation
Risk Summary
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 and Males of Reproductive Potential
Pregnancy Testing
VYXEOS can cause fetal harm when administered to a pregnant woman
[see Use in Specific Populations]. Verify the pregnancy status of females
of reproductive potential prior to initiating VYXEOS.
Contraception
Females
Advise females of reproductive potential to use effective contraception
during treatment with VYXEOS and for at least 6 months after the last dose.
Males
Advise males with female partners of reproductive potential to use
effective contraception during treatment with VYXEOS and for at least
6 months after the last dose.
Infertility
Based on findings of daunorubicin and cytarabine in animals, male
fertility may be compromised by treatment with VYXEOS.
Hospital Pharmacy - June 2020

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