Hospital Pharmacy - October 2017 - 582

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.



Table of Contents for the Digital Edition of Hospital Pharmacy - October 2017

Pharmacists and Medical Missions
Current FDA-Related Drug Information
Summaries of Safety Labeling Changes Approved By FDA- Boxed Warnings Highlights April-June 2017
Pharmaceutical Pipeline Update
Cholesterol Ester Transfer Protein Inhibitor Review
Formulary Drug Review
Ocrelizumab
Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review
Development of a Pharmacy Technician–Driven Program to Improve Vaccination Rates at an Academic Medical Center
Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Hemodialysis Patients
Multilayer Model of Pharmacy Participation in the Antimicrobial Stewardship Program at a Large Academic Medical Center
Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing
Impact of Respiratory Viral Panel Polymerase Chain Reaction Assay Turnaround Time on Length of Stay and Antibiotic Use in Patients With Respiratory Viral Illnesses
Administration of Injectable Vitamin K Orally
Hospital Pharmacy - October 2017 - 577
Hospital Pharmacy - October 2017 - 578
Hospital Pharmacy - October 2017 - 579
Hospital Pharmacy - October 2017 - 580
Hospital Pharmacy - October 2017 - 581
Hospital Pharmacy - October 2017 - 582
Hospital Pharmacy - October 2017 - 583
Hospital Pharmacy - October 2017 - 584
Hospital Pharmacy - October 2017 - 585
Hospital Pharmacy - October 2017 - 586
Hospital Pharmacy - October 2017 - 587
Hospital Pharmacy - October 2017 - 588
Hospital Pharmacy - October 2017 - Pharmacists and Medical Missions
Hospital Pharmacy - October 2017 - Current FDA-Related Drug Information
Hospital Pharmacy - October 2017 - Summaries of Safety Labeling Changes Approved By FDA- Boxed Warnings Highlights April-June 2017
Hospital Pharmacy - October 2017 - 592
Hospital Pharmacy - October 2017 - Pharmaceutical Pipeline Update
Hospital Pharmacy - October 2017 - Cholesterol Ester Transfer Protein Inhibitor Review
Hospital Pharmacy - October 2017 - 595
Hospital Pharmacy - October 2017 - Formulary Drug Review
Hospital Pharmacy - October 2017 - Ocrelizumab
Hospital Pharmacy - October 2017 - 598
Hospital Pharmacy - October 2017 - 599
Hospital Pharmacy - October 2017 - 600
Hospital Pharmacy - October 2017 - 601
Hospital Pharmacy - October 2017 - 602
Hospital Pharmacy - October 2017 - 603
Hospital Pharmacy - October 2017 - 604
Hospital Pharmacy - October 2017 - Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review
Hospital Pharmacy - October 2017 - 606
Hospital Pharmacy - October 2017 - 607
Hospital Pharmacy - October 2017 - 608
Hospital Pharmacy - October 2017 - 609
Hospital Pharmacy - October 2017 - 610
Hospital Pharmacy - October 2017 - 611
Hospital Pharmacy - October 2017 - 612
Hospital Pharmacy - October 2017 - 613
Hospital Pharmacy - October 2017 - 614
Hospital Pharmacy - October 2017 - Development of a Pharmacy Technician–Driven Program to Improve Vaccination Rates at an Academic Medical Center
Hospital Pharmacy - October 2017 - 616
Hospital Pharmacy - October 2017 - 617
Hospital Pharmacy - October 2017 - 618
Hospital Pharmacy - October 2017 - 619
Hospital Pharmacy - October 2017 - 620
Hospital Pharmacy - October 2017 - Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Hemodialysis Patients
Hospital Pharmacy - October 2017 - 622
Hospital Pharmacy - October 2017 - 623
Hospital Pharmacy - October 2017 - 624
Hospital Pharmacy - October 2017 - 625
Hospital Pharmacy - October 2017 - Multilayer Model of Pharmacy Participation in the Antimicrobial Stewardship Program at a Large Academic Medical Center
Hospital Pharmacy - October 2017 - 627
Hospital Pharmacy - October 2017 - 628
Hospital Pharmacy - October 2017 - 629
Hospital Pharmacy - October 2017 - 630
Hospital Pharmacy - October 2017 - 631
Hospital Pharmacy - October 2017 - 632
Hospital Pharmacy - October 2017 - Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing
Hospital Pharmacy - October 2017 - 634
Hospital Pharmacy - October 2017 - 635
Hospital Pharmacy - October 2017 - 636
Hospital Pharmacy - October 2017 - 637
Hospital Pharmacy - October 2017 - Impact of Respiratory Viral Panel Polymerase Chain Reaction Assay Turnaround Time on Length of Stay and Antibiotic Use in Patients With Respiratory Viral Illnesses
Hospital Pharmacy - October 2017 - 639
Hospital Pharmacy - October 2017 - 640
Hospital Pharmacy - October 2017 - 641
Hospital Pharmacy - October 2017 - 642
Hospital Pharmacy - October 2017 - Administration of Injectable Vitamin K Orally
Hospital Pharmacy - October 2017 - 644
Hospital Pharmacy - October 2017 - 645
Hospital Pharmacy - October 2017 - 646
Hospital Pharmacy - October 2017 - 647
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