Hospital Pharmacy - July/August 2018 - 202
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 - July/August 2018
Ed Board
TOC
Antibiotic Stewardship: The Health of the World Depends on It
ISMP Medication Error Report Analysis: CycloSPORINE Dispensing Errors
ISMP Adverse Drug Reactions
Summaries of Safety Labeling Changes Approved By FDA: Boxed Warnings Highlights January-March 2018
Restructuring a Pharmacy Department: Leadership Strategies for Managing Organizational Change
Angiotensin II
RxLegal: A Rapid Review of Right-To-Try
New Medications in the Treatment of Hereditary Transthyretin Amyloidosis
Significant Published Articles for Pharmacy Nutrition Support Practice in 2017
Utilization of Lean Techniques in Pharmacy Residency Training: Modifying the PGY1 Management and Leadership Experience
Impact of a Clinical Decision Support Tool on Cancer Pain Management in Opioid-Tolerant Inpatients
Lyme Carditis: A Case Report and Review of Management
Impact of the Implementation of Project Re-Engineered Discharge for Heart Failure patients at a Veterans Affairs Hospital at the Central Arkansas Veterans Healthcare System
Evaluation of Oritavancin Use at a Community Hospital
Hospital Pharmacy - July/August 2018 - Cover1
Hospital Pharmacy - July/August 2018 - Cover2
Hospital Pharmacy - July/August 2018 - 201
Hospital Pharmacy - July/August 2018 - 202
Hospital Pharmacy - July/August 2018 - 203
Hospital Pharmacy - July/August 2018 - 204
Hospital Pharmacy - July/August 2018 - 205
Hospital Pharmacy - July/August 2018 - Ed Board
Hospital Pharmacy - July/August 2018 - 207
Hospital Pharmacy - July/August 2018 - TOC
Hospital Pharmacy - July/August 2018 - 209
Hospital Pharmacy - July/August 2018 - 210
Hospital Pharmacy - July/August 2018 - 211
Hospital Pharmacy - July/August 2018 - 212
Hospital Pharmacy - July/August 2018 - 213
Hospital Pharmacy - July/August 2018 - Antibiotic Stewardship: The Health of the World Depends on It
Hospital Pharmacy - July/August 2018 - 215
Hospital Pharmacy - July/August 2018 - 216
Hospital Pharmacy - July/August 2018 - ISMP Medication Error Report Analysis: CycloSPORINE Dispensing Errors
Hospital Pharmacy - July/August 2018 - 218
Hospital Pharmacy - July/August 2018 - 219
Hospital Pharmacy - July/August 2018 - ISMP Adverse Drug Reactions
Hospital Pharmacy - July/August 2018 - 221
Hospital Pharmacy - July/August 2018 - 222
Hospital Pharmacy - July/August 2018 - Summaries of Safety Labeling Changes Approved By FDA: Boxed Warnings Highlights January-March 2018
Hospital Pharmacy - July/August 2018 - 224
Hospital Pharmacy - July/August 2018 - Restructuring a Pharmacy Department: Leadership Strategies for Managing Organizational Change
Hospital Pharmacy - July/August 2018 - 226
Hospital Pharmacy - July/August 2018 - 227
Hospital Pharmacy - July/August 2018 - 228
Hospital Pharmacy - July/August 2018 - 229
Hospital Pharmacy - July/August 2018 - Angiotensin II
Hospital Pharmacy - July/August 2018 - 231
Hospital Pharmacy - July/August 2018 - 232
Hospital Pharmacy - July/August 2018 - 233
Hospital Pharmacy - July/August 2018 - RxLegal: A Rapid Review of Right-To-Try
Hospital Pharmacy - July/August 2018 - 235
Hospital Pharmacy - July/August 2018 - New Medications in the Treatment of Hereditary Transthyretin Amyloidosis
Hospital Pharmacy - July/August 2018 - 237
Hospital Pharmacy - July/August 2018 - 238
Hospital Pharmacy - July/August 2018 - Significant Published Articles for Pharmacy Nutrition Support Practice in 2017
Hospital Pharmacy - July/August 2018 - 240
Hospital Pharmacy - July/August 2018 - 241
Hospital Pharmacy - July/August 2018 - 242
Hospital Pharmacy - July/August 2018 - 243
Hospital Pharmacy - July/August 2018 - 244
Hospital Pharmacy - July/August 2018 - 245
Hospital Pharmacy - July/August 2018 - 246
Hospital Pharmacy - July/August 2018 - Utilization of Lean Techniques in Pharmacy Residency Training: Modifying the PGY1 Management and Leadership Experience
Hospital Pharmacy - July/August 2018 - 248
Hospital Pharmacy - July/August 2018 - 249
Hospital Pharmacy - July/August 2018 - 250
Hospital Pharmacy - July/August 2018 - 251
Hospital Pharmacy - July/August 2018 - 252
Hospital Pharmacy - July/August 2018 - 253
Hospital Pharmacy - July/August 2018 - 254
Hospital Pharmacy - July/August 2018 - 255
Hospital Pharmacy - July/August 2018 - Impact of a Clinical Decision Support Tool on Cancer Pain Management in Opioid-Tolerant Inpatients
Hospital Pharmacy - July/August 2018 - 257
Hospital Pharmacy - July/August 2018 - 258
Hospital Pharmacy - July/August 2018 - 259
Hospital Pharmacy - July/August 2018 - 260
Hospital Pharmacy - July/August 2018 - 261
Hospital Pharmacy - July/August 2018 - 262
Hospital Pharmacy - July/August 2018 - Lyme Carditis: A Case Report and Review of Management
Hospital Pharmacy - July/August 2018 - 264
Hospital Pharmacy - July/August 2018 - 265
Hospital Pharmacy - July/August 2018 - Impact of the Implementation of Project Re-Engineered Discharge for Heart Failure patients at a Veterans Affairs Hospital at the Central Arkansas Veterans Healthcare System
Hospital Pharmacy - July/August 2018 - 267
Hospital Pharmacy - July/August 2018 - 268
Hospital Pharmacy - July/August 2018 - 269
Hospital Pharmacy - July/August 2018 - 270
Hospital Pharmacy - July/August 2018 - 271
Hospital Pharmacy - July/August 2018 - Evaluation of Oritavancin Use at a Community Hospital
Hospital Pharmacy - July/August 2018 - 273
Hospital Pharmacy - July/August 2018 - 274
Hospital Pharmacy - July/August 2018 - 275
Hospital Pharmacy - July/August 2018 - 276
Hospital Pharmacy - July/August 2018 - Cover3
Hospital Pharmacy - July/August 2018 - Cover4
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