New Drug Introduction: Savaysa / Edoxaban
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Black Box Warnings
Warnings and
Precautions
Pregnancy/Lactation
Pharmacokinetics
Drug Interactions –
Object Drugs
Drug Interactions –
Precipitant drugs
Adverse Effects
(Edoxaban 60mg)
[Warfarin]
Monitoring Efficacy
Monitoring Toxicity
Dosing
 Savaysa (edoxaban), is a factor Xa inhibitor to prevent stroke and
systemic embolism and treat deep vein thrombosis and pulmonary
embolism. Edoxaban inhibits free factor Xa, and prothrombinase activity
and inhibits thrombin-induced platelet aggregation.
 Daiichi Sankyo
 January 8th, 2015
 To reduce the risk of stroke and systemic embolism 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
 Active pathological bleeding
 Reduced efficacy in nonvalvular atrial fibrillation patients with CrCl >95
mL/minute – Avoid use in patients with CrCL >95 mL/minute
 Spinal/Epidural hematomas – with neuraxial anesthesia or spinal
puncture
 May increase the risk of bleeding; serious, potentially fatal bleeding
 Not recommended for use in patients with mechanical heart valves or
moderate to severe mitral stenosis
 Discontinue edoxaban at least 24 hours prior to elective surgery or
invasive procedures.
 Category: C
 Lactation Recommendation: Excretion in breast milk unknown/not
recommended.
 A – Bioavailability: 62%
 D – Vd: 107 L with ~55% protein binding
 M – Minimal via hydrolysis, conjugation and oxidation by CPY3A4;
predominant metabolite (M-4) is active (<10% of parent compound)
 E – Urine (primarily unchanged); renal clearance: ~50% of total
clearance. T1/2: 10 to 14 hours
 Anticoagulants, Antiplatelets, and Thrombolytics – Co-administration
may increase the risk of bleeding
 P-glycoprotein Inducers: ↓concentration of Edoxaban
Rifampin
 P-glycoprotein Inhibitors:  concentration of Edoxaban
NVAF: No dosage adjustment
DVT/PE: Consider Edoxaban dose reduction when used with
verapamil, quinidine, azithromycin, clarithromycin, erythromycin,
oral itraconazole or oral ketoconazole.
Vaginal Bleed (9%) [7.1%]
Cutaneous soft tissue bleed (5.9%) [10%]
Nose Bleeds (4.7%) [5.7%]
GI bleeding (4.2%) [3.6%]
Anemia (1.7%) [1.3%]
- Lower GI bleeding (3.4%) [3.1%]
 Routine monitoring of coagulation tests not required
 Monitor for signs and symptoms of bleeding including neurological
impairment.
 Deep vein thrombosis and pulmonary embolism: 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
Renal Adjustment
Hepatic Adjustment
 Deep vein thrombosis and pulmonary embolism:
CrCl ≥51 mL/minute: No dosage adjustment recommended.
CrCl 15 to 50 mL/minute: 30 mg once daily
CrCl <15 mL/minute: Use is not recommended.
 Nonvalvular atrial fibrillation:
CrCl >95 mL/minute: Use is not recommended.
CrCl 51 to 95 mL/minute: No dosage adjustment recommended.
CrCl 15 to 50 mL/minute: 30 mg once daily
CrCl <15 mL/minute: Use is not recommended.
 Hemodialysis: Total edoxaban exposure reduced by <7% during a 4hour dialysis session.
 Use is not recommended in patients with moderate or severe hepatic
impairment due to intrinsic coagulation abnormalities.
Cost:
Brand – Generic
Savaysa – edoxaban
Coumadin® - warfarin (generic)
Xarelto®– rivaroxaban
Eliquis®– apixaban
Dose
15 mg, 30 mg, 60mg tablets (30)
1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5
mg, 7.5 mg, 10mg tablets (30)
15 & 20 mg, starter pack (51)
10 mg, 15mg, 20mg tablets (30)
2.5 mg, 5mg tablets (60)
$ 30 day
$333
$4 (Discount Drug Plans)
$642
$378
$378
Summary
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Savaysa (Edoxaban) is a factor Xa inhibitor, indicated to prevent stroke and systemic embolism
in non-valvular atrial fibrillation and to treat deep vein thrombosis and pulmonary embolism.
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.
References:
1. Savaysa package insert. Daiichi Sankyo. January 2015.
2. Edoxaban: Drug information. Lexicomp Drug Information. Accessed through UpToDate on March 2, 2015.
3. Warfarin. Drug information. Lexicomp Drug Information. Accessed through UpToDate on March 2, 2015.
4. Rivaroxaban. Drug information. Lexicomp Drug Information. Accessed through UpToDate on March 2, 2015.
5. Apixaban. Drug information. Lexicomp Drug Information. Accessed through UpToDate on March 13, 2015.
Date Prepared: 03/17/2015
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Tiffany Wong, Pharm.D. Candidate, UNC Eshelman School of Pharmacy