Hospital Pharmacy - November 2017 - 654

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 - November 2017

AKD—The Time Between AKI and CKD: What Is the Role of the Pharmacist?
Letter to the Editor
Antithrombotic Therapy Post Endovascular Stenting for Superior Vena Cava Syndrome
Pharmaceutical Pipeline Update
Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
Formulary Drug Reviews
Etelcalcetide
Treatment of Hypertriglyceridemia-Induced Acute Pancreatitis With Insulin, Heparin, and Gemfibrozil: A Case Series
Evaluation of Antimicrobial Stewardship–Related Alerts Using a Clinical Decision Support System
Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution
Development of Institutional Guidelines for Management of Gram-Negative Bloodstream Infections: Incorporating Local Evidence
Underutilization of Aldosterone Antagonists in Heart Failure
Stability of Procainamide Injection in Clear Glass Vials and Polyvinyl Chloride Bags
Development of a Local Health-System Pharmacy Resident Society
Challenges and Solutions to New Manager Onboarding
Hospital Pharmacy - November 2017 - 649
Hospital Pharmacy - November 2017 - 650
Hospital Pharmacy - November 2017 - 651
Hospital Pharmacy - November 2017 - 652
Hospital Pharmacy - November 2017 - 653
Hospital Pharmacy - November 2017 - 654
Hospital Pharmacy - November 2017 - 655
Hospital Pharmacy - November 2017 - 656
Hospital Pharmacy - November 2017 - 657
Hospital Pharmacy - November 2017 - 658
Hospital Pharmacy - November 2017 - 659
Hospital Pharmacy - November 2017 - 660
Hospital Pharmacy - November 2017 - AKD—The Time Between AKI and CKD: What Is the Role of the Pharmacist?
Hospital Pharmacy - November 2017 - 662
Hospital Pharmacy - November 2017 - Letter to the Editor
Hospital Pharmacy - November 2017 - Pharmaceutical Pipeline Update
Hospital Pharmacy - November 2017 - Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
Hospital Pharmacy - November 2017 - Formulary Drug Reviews
Hospital Pharmacy - November 2017 - Etelcalcetide
Hospital Pharmacy - November 2017 - 668
Hospital Pharmacy - November 2017 - 669
Hospital Pharmacy - November 2017 - 670
Hospital Pharmacy - November 2017 - 671
Hospital Pharmacy - November 2017 - 672
Hospital Pharmacy - November 2017 - Treatment of Hypertriglyceridemia-Induced Acute Pancreatitis With Insulin, Heparin, and Gemfibrozil: A Case Series
Hospital Pharmacy - November 2017 - 674
Hospital Pharmacy - November 2017 - 675
Hospital Pharmacy - November 2017 - 676
Hospital Pharmacy - November 2017 - Evaluation of Antimicrobial Stewardship–Related Alerts Using a Clinical Decision Support System
Hospital Pharmacy - November 2017 - 678
Hospital Pharmacy - November 2017 - 679
Hospital Pharmacy - November 2017 - 680
Hospital Pharmacy - November 2017 - 681
Hospital Pharmacy - November 2017 - 682
Hospital Pharmacy - November 2017 - Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution
Hospital Pharmacy - November 2017 - 684
Hospital Pharmacy - November 2017 - 685
Hospital Pharmacy - November 2017 - 686
Hospital Pharmacy - November 2017 - 687
Hospital Pharmacy - November 2017 - 688
Hospital Pharmacy - November 2017 - Development of Institutional Guidelines for Management of Gram-Negative Bloodstream Infections: Incorporating Local Evidence
Hospital Pharmacy - November 2017 - 690
Hospital Pharmacy - November 2017 - 691
Hospital Pharmacy - November 2017 - 692
Hospital Pharmacy - November 2017 - 693
Hospital Pharmacy - November 2017 - 694
Hospital Pharmacy - November 2017 - 695
Hospital Pharmacy - November 2017 - Underutilization of Aldosterone Antagonists in Heart Failure
Hospital Pharmacy - November 2017 - 697
Hospital Pharmacy - November 2017 - 698
Hospital Pharmacy - November 2017 - 699
Hospital Pharmacy - November 2017 - 700
Hospital Pharmacy - November 2017 - 701
Hospital Pharmacy - November 2017 - Stability of Procainamide Injection in Clear Glass Vials and Polyvinyl Chloride Bags
Hospital Pharmacy - November 2017 - 703
Hospital Pharmacy - November 2017 - 704
Hospital Pharmacy - November 2017 - 705
Hospital Pharmacy - November 2017 - 706
Hospital Pharmacy - November 2017 - Development of a Local Health-System Pharmacy Resident Society
Hospital Pharmacy - November 2017 - 708
Hospital Pharmacy - November 2017 - 709
Hospital Pharmacy - November 2017 - Challenges and Solutions to New Manager Onboarding
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