Hospital Pharmacy - November 2017 - 653

Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug cannot
be directly compared to rates in the clinical trials of another drug and
may not reflect the rates observed in practice.

Adverse
Reaction
Pneumonia
(excluding fungal)
Sleep disorders
Bacteremia
(excluding sepsis)
Vomiting
Chills
Hypotension
Non-conduction
cardiotoxicity
Dizziness
Fungal infection
Hypertension
Hypoxia
Upper respiratory
infections (excluding
fungal)
Chest pain
Pyrexia
Catheter/device/
injection site reaction
Delirium
Pleural effusion
Anxiety
Pruritus
Sepsis (excluding
fungal)
Hemorrhoids
Petechiae
Renal insufficiency
Transfusion reactions
Visual impairment
(except bleeding)

The safety of VYXEOS was determined in a randomized trial for adults with
newly-diagnosed t-AML or AML-MRC which included 153 patients treated
with VYXEOS and 151 patients treated with a standard combination of
cytarabine and daunorubicin (7+3). At study entry, patients were required
to have a LVEF of at least 50% and a prior lifetime cumulative anthracycline
exposure less than 368 mg/m2 daunorubicin (or equivalent). On study,
the median number of cycles administered was 2 (range, 1-4 cycles)
on the VYXEOS arm and 1 (range, 1-4 cycles) on the control arm.
The median cumulative daunorubicin dose was 189 mg/m2
(range, 44-337 mg/m2) on the VYXEOS arm and 186 mg/m2
(range, 44-532 mg/m2) on the control arm.
Nine patients each on the VYXEOS arm (6%) and the control arm (6%)
had a fatal adverse reaction on treatment or within 30 days of therapy
that was not in the setting of progressive disease. Fatal adverse reactions
on the VYXEOS arm included infection, CNS hemorrhage, and respiratory
failure. Overall, all-cause day-30 mortality was 6% in the VYXEOS arm
and 11% in the control arm. During the first 60 days of the study, 14%
(21/153) of patients died in the VYXEOS arm vs. 21% (32/151) of patients
in the 7+3 treatment group.
The most common serious adverse reactions (incidence ≥5%) on the
VYXEOS arm were dyspnea, myocardial toxicity, sepsis, pneumonia,
febrile neutropenia, bacteremia and hemorrhage. Adverse reactions
led to discontinuation of VYXEOS in 18% (28/153) of patients, and
13% (20/151) in the control arm. The adverse reactions leading to
discontinuation on the VYXEOS arm included prolonged cytopenias,
infection, cardiotoxicity, respiratory failure, hemorrhage (GI and CNS),
renal insufficiency, colitis, and generalized medical deterioration. The
most common adverse reactions (incidence ≥25%) in patients on
the VYXEOS arm were 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.
The incidences of common adverse drug reactions during the induction
phase in Study 1 are presented in Table 2.
Table 2: Common Adverse Reactions (≥10% Incidence
in the VYXEOS arm) During the Induction Phase
Grades 3 to 5a
All Gradesa
Adverse
VYXEOS
7+3
VYXEOS
7+3
Reaction
N=153
N=151
N=153
N=151
n (%)
n (%)
n (%)
n (%)
Hemorrhage
107 (70)
74 (49)
15 (10)
9 (6)
Febrile Neutropenia
104 (68)
103 (68)
101 (66)
102 (68)
Rash
82 (54)
55 (36)
8 (5)
2 (1)
Edema
78 (51)
90 (60)
2 (2)
5 (3)
Nausea
72 (47)
79 (52)
1 (1)
1 (1)
Diarrhea/Colitis
69 (45)
100 (66)
4 (3)
10 (7)
Mucositis
67 (44)
69 (46)
2 (1)
7 (5)
Constipation
61 (40)
57 (38)
0
0
Musculoskeletal pain
58 (38)
52 (34)
5 (3)
4 (3)
Abdominal pain
51 (33)
45 (30)
3 (2)
3 (2)
Cough
51 (33)
34 (23)
0
1 (1)
Headache
51 (33)
36 (24)
2 (1)
1 (1)
Dyspnea
49 (32)
51 (34)
17 (11)
15 (10)
Fatigue
49 (32)
58 (38)
8 (5)
8 (5)
Arrhythmia
46 (30)
41 (27)
10 (7)
7 (5)
Decreased appetite
44 (29)
57 (38)
2 (1)
5 (3)

All Gradesa
VYXEOS
7+3
N=153
N=151
n (%)
n (%)

Grades 3 to 5a
VYXEOS
7+3
N=153
N=151
n (%)
n (%)

39 (26)

35 (23)

30 (20)

26 (17)

38 (25)

42 (28)

2 (1)

1 (1)

37 (24)

37 (25)

35 (23)

31 (21)

37 (24)
35 (23)
30 (20)

33 (22)
38 (25)
32 (21)

0
0
7 (5)

0
0
1 (1)

31 (20)

27 (18)

13 (9)

15 (10)

27 (18)
27 (18)
28 (18)
28 (18)

26 (17)
19 (13)
22 (15)
31 (21)

1 (1)
11 (7)
15 (10)
19 (12)

0
9 (6)
8 (5)
23 (15)

28 (18)

19 (13)

4 (3)

1 (1)

26 (17)
26 (17)

22 (15)
23 (15)

5 (3)
1 (1)

0
2 (1)

24 (16)

15 (10)

0

0

24 (16)
24 (16)
21 (14)
23 (15)

33 (22)
25 (17)
16 (11)
14 (9)

4 (3)
3 (2)
0
0

9 (6)
2 (1)
0
0

17 (11)

20 (13)

n/a

n/a

16 (11)
17 (11)
17 (11)
17 (11)

12 (8)
17 (11)
17 (11)
16 (11)

0
0
7 (5)
3 (2)

0
0
7 (5)
1 (1)

16 (11)

8 (5)

0

0

Adverse reactions were graded using NCI CTCAE version 3.0.

a

During the consolidation phase (both consolidation cycles pooled) the
two most common adverse reactions on the VYXEOS arm are the same
as those during induction, hemorrhagic events and febrile neutropenia.
These occurred at lower rates in the pooled consolidation phase (43%
and 29%, respectively), compared to the induction phase. All of the
common adverse reactions (≥10% incidence in the VYXEOS arm)
seen in the pooled consolidation phase were also seen in the induction
phase. These occurred at lower incidence in the consolidation phase,
with the exception of chills, dizziness and pyrexia, where the
incidences were relatively similar across the induction and
consolidation cycles.
Other notable adverse drug reactions that occurred in less than 10% of
patients treated with VYXEOS during induction or consolidation included:
* Ear and labyrinth disorders: Deafness, Deafness unilateral
* Eye Disorders: Eye conjunctivitis, Dry eye, Eye edema, Eye swelling,
Eye irritation, Eye pain, Ocular discomfort, Ocular hyperemia,
Periorbital edema, Scleral hyperemia
* Gastrointestinal disorders: Dyspepsia
* Psychiatric disorders: Hallucinations
* Respiratory, thoracic and mediastinal disorders: Pneumonitis



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
Hospital Pharmacy - November 2017 - 711
Hospital Pharmacy - November 2017 - 712
Hospital Pharmacy - November 2017 - 713
Hospital Pharmacy - November 2017 - 714
Hospital Pharmacy - November 2017 - 715
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