Hospital Pharmacy - February 2018 - 32
32
Hospital Pharmacy 53(1)
the betrixaban group and 1.1% in the enoxaparin
group (RR, 0.59; 95% CI, 0.35-0.97; P = .03).13 A
subgroup analysis also found that betrixaban decreased
the risk of all-cause stroke and ischemic stroke in
patients whose index event for enrollment was congestive heart failure or ischemic stroke.14
Comments: The study was conducted in North America,
Europe, South America, South Africa, Asia, and Australia.
This pivotal study was evaluated for betrixaban's approval
in the United States; the information included in the
betrixaban prescribing information is based on the overall
study population and not the subgroup cohorts. The study
was designed to assess the safety and efficacy of extendedduration oral betrixaban compared with standard-duration
enoxaparin for thromboprophylaxis in patients with acute
medical illness. Testing for superiority was done using a
fixed hierarchical sequence: superiority for primary end
point in cohort 1, followed by cohort 2, then the overall
study population followed by sequential analysis for various secondary end points. Superiority was not established
for cohort 1, so the results for the other primary and secondary end points can only be considered exploratory.
The inability to meet superiority may have been influenced by the smaller number of patients in cohort 1 compared with cohort 2 and the overall modified
intention-to-treat (mITT) efficacy population. Efficacy
was assessed using the mITT population (n = 7441) (ie,
patients who received at least 1 dose of study medication
and had an adequate assessment of VTE). Sensitivity
analysis was conducted using imputation to account for
missing data and found similar results. Subgroup analysis
of full- versus reduced-dose betrixaban found that the
80-mg dose achieved higher serum concentrations than
the 40-mg dose and was associated with improved efficacy across all cohorts relative to enoxaparin.15 Post hoc
analysis found that extended-duration betrixaban had an
approximately 30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration
enoxaparin.16
Limitations: Superiority was not established for cohort
1, so the results for the other primary and secondary end
points can only be considered exploratory. A new analysis process was used, in which the first primary end
point evaluated was in patients with higher risk, and
subsequent statistical analysis was based on a fixed
hierarchical sequence; if the between-group difference
of the previous analysis (ie, the first primary end point)
was not significant, then subsequent end points were
considered only exploratory. If the overall mITT population and cohort 2 had been used as the first 2 data sets
for this study, it would have been considered a success
and these 2 end points would not have been classified as
exploratory.
Contraindications, Warnings, and
Precautions
Contraindications
The contraindications for betrixaban are similar to those of
other oral factor Xa inhibitors: active pathological bleeding
and severe hypersensitivity reactions to the drug and its
inactive ingredients (ie, dextrose monohydrate, croscarmellose sodium, magnesium stearate, hard gelatin capsule; see
Table 3).1,6,7,8,9
Use of dabigatran is contraindicated in patients with
mechanical heart valves; safety and efficacy of factor Xa
inhibitors, including betrixaban, have not been evaluated in
this population. Contraindications to use of the factor Xa
inhibitors are summarized in Table 3.1,6,7,8,9
Warnings and Precautions
The warnings and precautions associated with betrixaban
therapy are similar to those of other oral factor Xa inhibitors
(see Table 3).1,6,7,8,9
Betrixaban prescribing information includes a boxed warning regarding the risk of spinal or epidural hematomas, which
may occur after neuraxial anesthesia or spinal puncture.
Frequently monitor patients for signs and symptoms of neurological impairment (eg, numbness or weakness of legs, bowel
or bladder dysfunction). The risk of these events may be
increased by the use of indwelling epidural catheters or by concomitant use of medical products affecting hemostasis. Do not
remove an epidural catheter earlier than 72 hours after the last
administration of betrixaban. Do not administer the next betrixaban dose earlier than 5 hours after the removal of the catheter.
If traumatic puncture occurs, delay the administration of betrixaban for 72 hours. Hematomas may result in long-term or permanent paralysis. If neurological signs or symptoms are noted,
urgent diagnosis and treatment are necessary.1
Use of oral factor Xa inhibitors, including betrixaban, is
associated with an increased risk of bleeding, which can be
fatal. Concomitant use of drugs affecting hemostasis (eg,
aspirin and other antiplatelet agents, other anticoagulants,
heparin, thrombolytic agents, selective serotonin reuptake
inhibitors [SSRIs], serotonin-norepinephrine reuptake
inhibitors [SNRIs], nonsteroidal anti-inflammatory drugs
[NSAIDs]) increases the risk of bleeding. Patients should
be evaluated for signs or symptoms of blood loss, and therapy should be discontinued in patients with active pathological bleeding. There is no established way to reverse the
anticoagulant effects of betrixaban; effects of hemodialysis
are unknown, and protamine sulfate, vitamin K, and
tranexamic acid are not expected to reverse betrixaban's
anticoagulant activity.1
Patients with severe renal impairment (CrCl 15 mL/min
to less than 30 mL/min) taking betrixaban may have an
Table of Contents for the Digital Edition of Hospital Pharmacy - February 2018
Ed Board
TOC
Editorial
The Evolving Frontier of Digital Health: Opportunities for Pharmacists on the Horizon
Letter to the Editor
Immediate Attention Required: Another Shortage
ISMP Adverse Drug Reactions
ISMP Adverse Drug Reactions
Current FDA-Related Drug Information
Summaries of Safety Labeling Changes Approved By FDA: Boxed Warnings Highlights July-September 2017
ISMP Medication Error Report Analysis
Common Missteps With Medication Safety: Rolling a Single Dice, Ineffective Strategies, and Unexecuted Action Plans
Formulary Drug Reviews
Betrixaban
Pharmaceutical Pipeline Update
Antibiotics in Development for the Treatment of Resistant Bacterial Disease
Articles
Evaluation of the Incidence of Ibuprofen Administration in Alcohol and Opioid Detoxification Patients With Concomitant Thrombocytopenia
Antimicrobial Utilization Pattern in Pediatric Patients in Tertiary Care Hospital, Eastern Ethiopia: The Need for Antimicrobial Stewardship
Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report
Outcomes From a Pharmacist: Led Proton Pump Inhibitor Stewardship Program at a Single Institution
Corrigendum
Hospital Pharmacy - February 2018 - Cover1
Hospital Pharmacy - February 2018 - Cover2
Hospital Pharmacy - February 2018 - 1
Hospital Pharmacy - February 2018 - 2
Hospital Pharmacy - February 2018 - 3
Hospital Pharmacy - February 2018 - Ed Board
Hospital Pharmacy - February 2018 - TOC
Hospital Pharmacy - February 2018 - Editorial
Hospital Pharmacy - February 2018 - The Evolving Frontier of Digital Health: Opportunities for Pharmacists on the Horizon
Hospital Pharmacy - February 2018 - 8
Hospital Pharmacy - February 2018 - 9
Hospital Pharmacy - February 2018 - 10
Hospital Pharmacy - February 2018 - Letter to the Editor
Hospital Pharmacy - February 2018 - Immediate Attention Required: Another Shortage
Hospital Pharmacy - February 2018 - 13
Hospital Pharmacy - February 2018 - ISMP Adverse Drug Reactions
Hospital Pharmacy - February 2018 - ISMP Adverse Drug Reactions
Hospital Pharmacy - February 2018 - 16
Hospital Pharmacy - February 2018 - Current FDA-Related Drug Information
Hospital Pharmacy - February 2018 - Summaries of Safety Labeling Changes Approved By FDA: Boxed Warnings Highlights July-September 2017
Hospital Pharmacy - February 2018 - 19
Hospital Pharmacy - February 2018 - 20
Hospital Pharmacy - February 2018 - 21
Hospital Pharmacy - February 2018 - 22
Hospital Pharmacy - February 2018 - 23
Hospital Pharmacy - February 2018 - ISMP Medication Error Report Analysis
Hospital Pharmacy - February 2018 - Common Missteps With Medication Safety: Rolling a Single Dice, Ineffective Strategies, and Unexecuted Action Plans
Hospital Pharmacy - February 2018 - 26
Hospital Pharmacy - February 2018 - 27
Hospital Pharmacy - February 2018 - Formulary Drug Reviews
Hospital Pharmacy - February 2018 - Betrixaban
Hospital Pharmacy - February 2018 - 30
Hospital Pharmacy - February 2018 - 31
Hospital Pharmacy - February 2018 - 32
Hospital Pharmacy - February 2018 - 33
Hospital Pharmacy - February 2018 - 34
Hospital Pharmacy - February 2018 - 35
Hospital Pharmacy - February 2018 - 36
Hospital Pharmacy - February 2018 - Pharmaceutical Pipeline Update
Hospital Pharmacy - February 2018 - Antibiotics in Development for the Treatment of Resistant Bacterial Disease
Hospital Pharmacy - February 2018 - 39
Hospital Pharmacy - February 2018 - Articles
Hospital Pharmacy - February 2018 - Evaluation of the Incidence of Ibuprofen Administration in Alcohol and Opioid Detoxification Patients With Concomitant Thrombocytopenia
Hospital Pharmacy - February 2018 - 42
Hospital Pharmacy - February 2018 - 43
Hospital Pharmacy - February 2018 - Antimicrobial Utilization Pattern in Pediatric Patients in Tertiary Care Hospital, Eastern Ethiopia: The Need for Antimicrobial Stewardship
Hospital Pharmacy - February 2018 - 45
Hospital Pharmacy - February 2018 - 46
Hospital Pharmacy - February 2018 - 47
Hospital Pharmacy - February 2018 - 48
Hospital Pharmacy - February 2018 - 49
Hospital Pharmacy - February 2018 - 50
Hospital Pharmacy - February 2018 - 51
Hospital Pharmacy - February 2018 - 52
Hospital Pharmacy - February 2018 - 53
Hospital Pharmacy - February 2018 - 54
Hospital Pharmacy - February 2018 - Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report
Hospital Pharmacy - February 2018 - 56
Hospital Pharmacy - February 2018 - 57
Hospital Pharmacy - February 2018 - 58
Hospital Pharmacy - February 2018 - Outcomes From a Pharmacist: Led Proton Pump Inhibitor Stewardship Program at a Single Institution
Hospital Pharmacy - February 2018 - 60
Hospital Pharmacy - February 2018 - 61
Hospital Pharmacy - February 2018 - 62
Hospital Pharmacy - February 2018 - 63
Hospital Pharmacy - February 2018 - 64
Hospital Pharmacy - February 2018 - 65
Hospital Pharmacy - February 2018 - 66
Hospital Pharmacy - February 2018 - 67
Hospital Pharmacy - February 2018 - Corrigendum
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Hospital Pharmacy - February 2018 - Cover4
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