Hospital Pharmacy - October 2017 - 580
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]
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
Hospital Pharmacy - October 2017 - 648
Hospital Pharmacy - October 2017 - 649
Hospital Pharmacy - October 2017 - 650
Hospital Pharmacy - October 2017 - 651
Hospital Pharmacy - October 2017 - 652
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2020
https://www.nxtbook.com/nxtbooks/sage/psychologicalscience_demo
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2020
https://www.nxtbook.com/nxtbooks/sage/fai_202009
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_august2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2019
https://www.nxtbook.com/nxtbooks/sage/fai_201909
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_july2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2019
https://www.nxtbook.com/nxtbooks/sage/canadianpharmacistsjournal_05062019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2019
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201903
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2018
https://www.nxtbook.com/nxtbooks/sage/tec_20180810
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2018
https://www.nxtbook.com/nxtbooks/sage/fai_201807
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2018
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201803
https://www.nxtbook.com/nxtbooks/sage/slas_discovery_201712
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_november2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_september2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2017
https://www.nxtbook.com/nxtbooks/sage/fai_supplement_201709
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_may2017
https://www.nxtbook.com/nxtbooks/sage/fai_201706
https://www.nxtbook.com/nxtbooks/sage/fai_201607
https://www.nxtbookmedia.com