Edoxaban: Difference between revisions

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{{Drugbox
{{DrugProjectFormSinglePage
| Verifiedfields = changed
|authorTag={{MN}}
| verifiedrevid = 415900881
|genericName=Edoxaban tosylate
| IUPAC_name = ''N'''-(5-chloropyridin-2-yl)-''N''-[(1''S'',2''R'',4''S'')-4-(dimethylcarbamoyl)-2-[(5-methyl-6,7-dihydro-4''H''-[1,3]thiazolo[5,4-c]pyridine-2-carbonyl)amino]cyclohexyl]oxamide
|aOrAn=a
| image = Edoxaban.png
|drugClass=[[factor Xa]] inhibitor
| width = 200
|indicationType=prevention
|indication=[[stroke]] and [[systemic embolism]] (SE) in patients with [[nonvalvular atrial fibrillation]] ([[NVAF]]). Is also indicated for the treatment of [[deep vein thrombosis]] ([[DVT]]) and [[pulmonary embolism]] ([[PE]]) following 5 to 10 days of initial therapy with a [[parenteral]] [[anticoagulant]]
|adverseReactions=[[bleeding]] and [[anemia]] in the treatment of [[NVAF]] (≥ 5%) and [[bleeding]], [[rash]], abnormal [[liver function]] tests and [[anemia]] in the treatment of [[DVT]] and [[PE]] (≥ 1%)
|hasBlackBoxWarning=Yes
|blackBoxWarningTitle=<span style="color:#FF0000;">(A) REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH CREATININE CLEARANCE (CRCL) > 95 ML/MIN (B) PREMATURE DISCONTINUATION OF EDOXABAN TOSYLATE INCREASES THE RISK OF ISCHEMIC EVENTS (C) SPINAL/EPIDURAL HEMATOMA</span>
|blackBoxWarningBody=<i><span style="color:#FF0000;">
A. REDUCED EFFICACY IN [[NONVALVULAR ATRIAL FIBRILLATION]] PATIENTS WITH [[CRCL]] > 95 ML/MIN


<!--Clinical data-->
SAVAYSA should not be used in patients with CrCL > 95 mL/min. In the ENGAGE AF-TIMI 48 study, nonvalvular atrial fibrillation patients with CrCL > 95 mL/min had an increased rate of ischemic stroke with SAVAYSA 60 mg once daily compared to patients treated with [[warfarin]]. In these patients another [[anticoagulant]] should be used.
| tradename = Lixiana
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!--            / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL        / P      / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC                  / Rx-only  / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration = 


<!--Pharmacokinetic data-->
B. PREMATURE DISCONTINUATION OF EDOXABAN TOSYLATE INCREASES THE RISK OF [[ISCHEMIC]] EVENTS
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| excretion = 


<!--Identifiers-->
Premature discontinuation of any [[oral anticoagulant]] in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If SAVAYSA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant as described in the transition guidance.
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 912273-65-5
| ATC_prefix = none
| PubChem = 25022378
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = 
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = NDU3J18APO
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D09710


<!--Chemical data-->
C. SPINAL/EPIDURAL [[HEMATOMA]]
| C=24 | H=30 | Cl=1 | N=7 | O=4 | S=1
| molecular_weight = 548.056 g/mol
| smiles = 
}}
__NOTOC__
{{SI}}
{{CMG}}


==Overview==
Epidural or spinal hematomas may occur in patients treated with SAVAYSA who are receiving [[neuraxial anesthesia]] or undergoing [[spinal puncture]]. These hematomas may result in long-term or permanent [[paralysis]]. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:


'''Edoxaban''' ([[International Nonproprietary Name|INN]], codenamed '''DU-176b''', trade name '''Lixiana''') is an [[anticoagulant]] drug which acts as a [[direct factor Xa inhibitor]]. It is being developed by [[Daiichi Sankyo]]. It was approved in July 2011 in Japan for prevention of venous thromboembolisms (VTE) following lower-limb orthopedic surgery.<ref name="url_Daiichi_Sankyo_Europe_GmbH">{{cite web | url = http://www.daiichi-sankyo.eu/media/press-news-in-english/news-detail/article/first-market-approval-in-japan-for-lixianaR-edoxaban.html | title = First market approval in Japan for LIXIANA (Edoxaban)  | date =  2011-04-22 | work = Press Release | publisher = Daiichi Sankyo Europe GmbH }}</ref>
:*use of indwelling [[epidural catheters]]
:*concomitant use of other drugs that affect [[hemostasis]], such as [[nonsteroidal anti-inflammatory drugs]] (NSAIDs), [[platelet inhibitors]], other [[anticoagulants]]
:*a history of traumatic or repeated epidural or spinal punctures
:*a history of spinal deformity or spinal surgery
:*optimal timing between the administration of SAVAYSA and neuraxial procedures is not known


== Preclinical Research ==


In animal studies, edoxaban is potent, selective for factor Xa and has good oral bioavailability.<ref name="pmid18624979">{{cite journal | author = Furugohri T, Isobe K, Honda Y, Kamisato-Matsumoto C, Sugiyama N, Nagahara T, Morishima Y, Shibano T | title = DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles | journal = J. Thromb. Haemost. | volume = 6 | issue = 9 | pages = 1542–9 |date=September 2008  | pmid = 18624979 | doi = 10.1111/j.1538-7836.2008.03064.x }}</ref>
Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.


== Clinical Trials ==
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.
</span></i>


Several Phase II [[clinical trial]]s have been conducted, for example for [[thromboprophylaxis]] after [[total hip replacement]]<ref>{{pmid|20589317}}</ref> (phase III early results compare well to [[enoxaparin]]<ref name=Dec2010>{{cite web |url=http://www.genengnews.com/gen-news-highlights/phase-iii-trial-finds-edoxaban-outclasses-enoxaparin-in-preventing-venous-thromboembolic-events/81244351/ |title=Phase III Trial Finds Edoxaban Outclasses Enoxaparin in Preventing Venous Thromboembolic Events |date=8 Dec 2010 }}</ref>), and for [[stroke]] prevention in patients with [[atrial fibrillation]]<ref name="pmid">{{cite journal | author = Weitz JI, Connolly SJ, Patel I, Salazar D, Rohatagi S, Mendell J, Kastrissios H, Jin J, Kunitada S | title = Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation | journal = Thromb. Haemost. | volume = 104 | issue = 3 | pages = 633–41 |date=September 2010  | pmid = | doi = 10.1160/TH10-01-0066 }}</ref> (phase III has completed enrollment<ref name=Dec2010/>).
|fdaLIADAdult=
======Indications======
======Dosage======
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Pimavanserin in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Pimavanserin in adult patients.
|fdaLIADPed=Safety and effectiveness have not been established in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Pimavanserin in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Pimavanserin in pediatric patients.
|contraindications=
|warnings=
|clinicalTrials=
|postmarketing=
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|FDAPregCat=
|useInPregnancyFDA=
|useInLaborDelivery=
|useInNursing=
|useInPed=
|useInGeri=
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|useInImmunocomp=
|othersTitle=
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|overdose=
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A large phase III trial showed that edoxaban was non inferior to [[warfarin]] in preventing recurrent venous thromboembolic events with fewer episodes of major bleeding.<ref name="pmid23991658">{{cite journal | author = | title = Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism | journal = N. Engl. J. Med. | volume = | issue = | pages = |date=August 2013  | pmid = 23991658 | doi = 10.1056/NEJMoa1306638 }}</ref> This paper follows similar recent major trials showing similar results for the other new [[factor Xa inhibitor]]s, [[rivaroxaban]] and [[apixaban]].<ref name="pmid">{{cite journal | author = Tahir F, Riaz H, Riaz T, Badshah MB, Riaz IB, Hamza A, Mohiuddin H | title = The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature | journal = Thromb J | volume = 11 | issue = 1 | pages = 18 |date=September 2013  | pmid = | doi = 10.1186/1477-9560-11-18 }}</ref>
|mechAction=
 
|structure=
==References==
|PD=
{{reflist|2}}
|PK=
 
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of [[Fertility]]======
{{Antithrombotics}}
|clinicalStudies=
 
|howSupplied=
[[Category:Drug]]
|storage=
[[Category:Cardiovascular Drugs]]
|packLabel=[[File:pima.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[Category:Anticoagulants]]
|fdaPatientInfo=
|brandNames=
}}

Revision as of 15:57, 7 February 2017

Edoxaban
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino [2]

Disclaimer

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Black Box Warning

(A) REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH CREATININE CLEARANCE (CRCL) > 95 ML/MIN (B) PREMATURE DISCONTINUATION OF EDOXABAN TOSYLATE INCREASES THE RISK OF ISCHEMIC EVENTS (C) SPINAL/EPIDURAL HEMATOMA
See full prescribing information for complete Boxed Warning.

A. REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH CRCL > 95 ML/MIN

SAVAYSA should not be used in patients with CrCL > 95 mL/min. In the ENGAGE AF-TIMI 48 study, nonvalvular atrial fibrillation patients with CrCL > 95 mL/min had an increased rate of ischemic stroke with SAVAYSA 60 mg once daily compared to patients treated with warfarin. In these patients another anticoagulant should be used.

B. PREMATURE DISCONTINUATION OF EDOXABAN TOSYLATE INCREASES THE RISK OF ISCHEMIC EVENTS

Premature discontinuation of any oral anticoagulant in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If SAVAYSA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant as described in the transition guidance.

C. SPINAL/EPIDURAL HEMATOMA

Epidural or spinal hematomas may occur in patients treated with SAVAYSA who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:


Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

Overview

Edoxaban is a factor Xa inhibitor that is FDA approved for the prevention of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF). Is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5 to 10 days of initial therapy with a parenteral anticoagulant. There is a Black Box Warning for this drug as shown here. Common adverse reactions include bleeding and anemia in the treatment of NVAF (≥ 5%) and bleeding, rash, abnormal liver function tests and anemia in the treatment of DVT and PE (≥ 1%).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications
Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness have not been established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in pediatric patients.

Contraindications

There is limited information regarding Edoxaban Contraindications in the drug label.

Warnings

(A) REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH CREATININE CLEARANCE (CRCL) > 95 ML/MIN (B) PREMATURE DISCONTINUATION OF EDOXABAN TOSYLATE INCREASES THE RISK OF ISCHEMIC EVENTS (C) SPINAL/EPIDURAL HEMATOMA
See full prescribing information for complete Boxed Warning.

A. REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH CRCL > 95 ML/MIN

SAVAYSA should not be used in patients with CrCL > 95 mL/min. In the ENGAGE AF-TIMI 48 study, nonvalvular atrial fibrillation patients with CrCL > 95 mL/min had an increased rate of ischemic stroke with SAVAYSA 60 mg once daily compared to patients treated with warfarin. In these patients another anticoagulant should be used.

B. PREMATURE DISCONTINUATION OF EDOXABAN TOSYLATE INCREASES THE RISK OF ISCHEMIC EVENTS

Premature discontinuation of any oral anticoagulant in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If SAVAYSA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant as described in the transition guidance.

C. SPINAL/EPIDURAL HEMATOMA

Epidural or spinal hematomas may occur in patients treated with SAVAYSA who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:


Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

There is limited information regarding Edoxaban Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Edoxaban Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Edoxaban Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Edoxaban Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Edoxaban in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Edoxaban in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Edoxaban during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Edoxaban in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Edoxaban in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Edoxaban in geriatric settings.

Gender

There is no FDA guidance on the use of Edoxaban with respect to specific gender populations.

Race

There is no FDA guidance on the use of Edoxaban with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Edoxaban in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Edoxaban in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Edoxaban in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Edoxaban in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Edoxaban Administration in the drug label.

Monitoring

There is limited information regarding Edoxaban Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Edoxaban and IV administrations.

Overdosage

There is limited information regarding Edoxaban overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Chemical structure of Edoxaban
Edoxaban
Systematic (IUPAC) name
?
Identifiers
CAS number ?
ATC code ?
PubChem ?
Chemical data
Formula ?
Mol. mass ?
Pharmacokinetic data
Bioavailability ?
Metabolism ?
Half life ?
Excretion ?
Therapeutic considerations
Pregnancy cat.

?

Legal status
Routes ?

Mechanism of Action

There is limited information regarding Edoxaban Mechanism of Action in the drug label.

Structure

There is limited information regarding Edoxaban Structure in the drug label.

Pharmacodynamics

There is limited information regarding Edoxaban Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Edoxaban Pharmacokinetics in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Clinical Studies

There is limited information regarding Edoxaban Clinical Studies in the drug label.

How Supplied

There is limited information regarding Edoxaban How Supplied in the drug label.

Storage

There is limited information regarding Edoxaban Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Edoxaban |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

This image is provided by the National Library of Medicine.

{{#ask: Label Page::Edoxaban |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Edoxaban Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Edoxaban interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Edoxaban Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Edoxaban Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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