Transcript savaysa

Savaysa™ - Edoxaban
Manufacturer:
Daiichi Sankyo
FDA Approval Date: 01/08/2015
Savaysa™ - Edoxaban
Clinical Application
• Indications:
• To reduce the risk of stroke and systemic embolism
(SE) in patients with nonvalvular atrial fibrillation.
• Treatment of deep vein thrombosis (DVT) and
pulmonary embolism (PE) following 5 to 10 days of
initial therapy with a parenteral anticoagulant.
• Place in therapy:
• Edoxban is the third factor Xa inhibitor approved for
NVAF
• Noninferior to warfarin, with significant lower risk of
bleeding
• Impaired renal function
Savaysa™ - Edoxaban
Clinical Application
• Contraindications:
• Active pathological bleeding
• Black Box Warnings:
• Reduced efficacy in nonvalvular atrial fibrillation
patients with CrCl >95 mL/minute – Edoxaban
should not be used in patients with CrCL >95
mL/minute.
• Premature discontinuation of edoxaban increases
the risk of ischemic events
• Spinal/Epidural hematomas – Epidural or spinal
hematomas may occur in patients treated with
edoxaban who are receiving neuraxial anesthesia or
undergoing spinal puncture.
Savaysa™ - Edoxaban
Clinical Application
• Warnings / Precautions:
• May increase the risk of bleeding; serious,
potentially fatal bleeding may occur.
• Not recommended for use in patients with
mechanical heart valves or moderate to
severe mitral stenosis; safety and efficacy
have not been established.
• Patients with DVT and/or PE and body
weight ≤60 kg, reduce dose to 30mg
• Discontinue edoxaban at least 24 hours
prior to elective surgery or invasive
procedures.
Savaysa™ - Edoxaban
Clinical Application
• Pregnancy:
• Category C
• Lactation:
• Excretion in breast milk unknown/not
recommended.
• Due to the potential for serious adverse
reactions in the nursing infant, the decision
to discontinue nursing or to discontinue the
drug should be made taking into account the
importance of treatment to the mother.
Savaysa™ - Edoxaban
Drug Facts
• Pharmacology:
• Edoxaban, a selective factor Xa
inhibitor, inhibits free factor Xa and
prothrombinase activity and inhibits
thrombin-induced platelet aggregation.
• Inhibition of factor Xa in the
coagulation cascade reduces thrombin
generation and thrombus formation.
Savaysa™ - Edoxaban
Drug Facts
• Pharmacokinetics:
A
Bioavailability: 62%
D
Vd: 107 L with ~55% protein binding
M
Not significantly metabolized
E
Urine (primarily unchanged); renal clearance:
~50% of total clearance.
T1/2: 10 to 14 hours
Savaysa™ - Edoxaban
Drug Interactions
• Drug Interactions – Object Drugs:
• Anticoagulants, Antiplatelets, and
Thrombolytics – Co-administration may
increase the risk of bleeding
(anticoagulants, aspirin, other platelet
aggregation inhibitors, and/or NSAIDs)
Savaysa™ - Edoxaban
Drug Interactions
• Drug Interactions – Precipitant Drugs:
• P-glycoprotein Inducers: ↓concentration of
Edoxaban
• Rifampin
• P-glycoprotein Inhibitors:  concentration of
Edoxaban
• Verapamil, quinidine or the short-term use of
azithromycin, clarithromycin, erythromycin, oral
itraconazole or oral ketoconazole.
• NVAF: No dosage adjustment
• DVT/PE: May need to dose reduce Edoxaban
Savaysa™ - Edoxaban
Adverse Effects
Edoxaban vs. Warfarin:
60mg
Warfarin
Vaginal Bleed
9.0%
7.1%
Cutaneous soft tissue bleed
5.9%
10.0%
Nose Bleeds
4.7%
5.7%
Gastrointestinal bleeding
4.2%
3.6%
Lower gastrointestinal
3.4%
3.1%
Anemia
1.7%
1.3%
Savaysa™ - Edoxaban
Monitoring Parameters
• Efficacy Monitoring:
• Routine monitoring of coagulation tests not
required
• Toxicity Monitoring:
• Monitor for signs and symptoms of bleeding
including neurological impairment.
Savaysa™ - Edoxaban
Prescription Information
• Dosing:
• DVT/PE: Oral: 60 mg once daily after 5 to 10 days of
initial therapy with a parenteral anticoagulant.
• Patient weight ≤60 kg: 30 mg once daily
• Concomitant therapy with specific P-gp
inhibitors: 30 mg once daily
• Nonvalvular atrial fibrillation: Oral: 60 mg once daily
• Cost: – Uptodate (03/01/2015)
Brand – Generic
Savaysa –
edoxaban
Dose
$ 30 day
15 mg, 30mg, 60mg tablets
(30)
$333
Edoxaban versus Warfarin in Patients with Atrial Fibrillation
SAVAYSA™ - EDOXABAN
LITERATURE REVIEW
Giugliano RP, et al. NEJM 2013; 369:2093-2104
Savaysa™ - Edoxaban
Literature Review
• Phase 3, randomized, double-blind, doubledummy, non-inferiority
• Primary Endpoint: time to the first adjudicated
stroke (ischemic or hemorrhagic) or systemic
embolic event
• Principal safety end point – adjudicated major
bleeding
• Secondary composite end points: stroke, systemic
embolic event, or death from cardiovascular causes
(including bleeding)
• Treatment: 1:1:1 ratio, warfarin, high-dose
(60mg) or low-dose (30mg) edoxaban
Giugliano RP, et al. NEJM 2013; 369:2093-2104
Savaysa™ - Edoxaban
Literature Review
• Inclusion Criteria
• Age ≥21 years old
• History of AF of any duration within the prior 12
months
• CHADS2 index score ≥2
• Exclusion Criteria
• AF due to a reversible disorder
• Severe renal dysfunction (CrCl < 30 mL/min)
• Condition associated with a high risk of
bleeding
• Moderate or severe mitral stenosis
Giugliano RP, et al. NEJM 2013; 369:2093-2104
Savaysa™ - Edoxaban
Literature Review
Warfarin
(N=7036)
High-Dose
Edoxaban
(N=7035)
Low-Dose
Edoxaban
(N=7034)
72
72
72
37.5%
37.9%
38.8%
≤3
77.4%
77.1%
77.8%
4-6
22.6%
22.9%
22.2%
CrCl ≤50 ml/min
19.3%
19.6%
19.0%
Weight ≤60 kg
10.0%
9.7%
9.9%
Use of verapamil or quinidine
3.5%
3.7%
3.7%
Patient Characteristic
(n=21,105)
Age (yr) – Median
Female
CHADS2 score
Dose reduction at
randomization
Giugliano RP, et al. NEJM 2013; 369:2093-2104
Savaysa™ - Edoxaban
Literature Review
• Results: (Median follow-up 2.8yrs)
• The annualized rate of the primary end point of
stroke or systemic embolism
• 1.50% with warfarin
• 1.18% with high-dose edoxaban (P<0.001 for
noninferiority)
• 1.61% with low-dose edoxaban (P=0.005 for
noninferiority)
• The annualized rate of major bleeding
• 3.43% with warfarin
• 2.75% with high-dose edoxaban (P<0.001)
• 1.61% with low-dose edoxaban (P<0.001).
Giugliano RP, et al. NEJM 2013; 369:2093-2104
Savaysa™ - Edoxaban
Literature Review
• Conclusion
• Both once-daily regimens of edoxaban
were noninferior to warfarin
• Edoxaban was associated with
significantly lower rates of bleeding and
death from cardiovascular causes.
Giugliano RP, et al. NEJM 2013; 369:2093-2104
Savaysa™ - Edoxaban
Summary
• Savaysa™ (Edoxaban) is a factor Xa inhibitor, indicated
to prevent stroke and systemic embolism in non-valvular
atrial fibrillation and to treat DVT and PE. When used in
the treatment of DVT/PE edoxaban requires 5 to 10 days
of initial therapy with a parenteral anticoagulant.
• Edoxaban is typically given as a once daily 60mg dose,
but should be administered at lower doses for patients
with impaired renal or hepatic function or if the patient
weights ≤60 kg.
• Edoxaban should not be used in NVAF patients with
CrCL >95 mL/minute.
• The most common side effects of edoxaban include;
vaginal, cutaneous soft tissue, nose, and GI bleeding.
Savaysa™ - Edoxaban
References
1. Savaysa package insert. Daiichi Sankyo. January
2015.
2. Edoxaban: Drug information. Lexicomp Drug
Information. Accessed through UpToDate on
March 2, 2015.
3. Giugliano RP, et al. NEJM 2013; 369:2093-2104.