Apixaban Use in Adults with Severe Kidney Disease



Canberra Hospital and Health ServicesClinical GuidelineApixaban Use in Adults with Severe Kidney DiseaseContents TOC \h \z \t "Heading 1,1,Heading 2,2" Contents PAGEREF _Toc520453900 \h 1Guideline Statement PAGEREF _Toc520453901 \h 2Background PAGEREF _Toc520453902 \h 2Key Objective PAGEREF _Toc520453903 \h 2Alerts PAGEREF _Toc520453904 \h 2Scope PAGEREF _Toc520453905 \h 2Section 1 – Apixaban Target Trough Levels and Dosage PAGEREF _Toc520453906 \h 3Section 2 – Planned Elective Surgery PAGEREF _Toc520453907 \h 3Section 3 – Haemorrhage PAGEREF _Toc520453908 \h 4Implementation PAGEREF _Toc520453909 \h 4Related Policies, Procedures, Guidelines and Legislation PAGEREF _Toc520453910 \h 5References PAGEREF _Toc520453911 \h 5Definition of Terms PAGEREF _Toc520453912 \h 6Search Terms PAGEREF _Toc520453913 \h 6Attachments PAGEREF _Toc520453914 \h 6Attachment 1 – Apixaban Clinician Discussion Points PAGEREF _Toc520453915 \h 7Guideline StatementBackgroundNovel Oral Anticoagulants (NOACs) are a warfarin alternative that are indicated by preventing recurrent venous thromboembolism and arterial thromboembolism related to atrial fibrillation. In Australia, use at a creatinine clearance below 25 mL/min is listed as a contraindication by the Therapeutic Goods Administration. This contra-indication pre-dates more recent data on the pharmacokinetics of NOACs in dialysis patients. Apixaban has the least renal excretion of any NOAC. A multi-dose study in dialysis patients indicated that a dose of apixaban 2.5mg twice daily resulted in a predicted drug exposure equivalent to a 5mg twice daily dose in subjects with normal renal functionPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXZyYWthbmFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVh

cj48UmVjTnVtPjk0NDwvUmVjTnVtPjxEaXNwbGF5VGV4dD48c3R5bGUgZmFjZT0ic3VwZXJzY3Jp

cHQiPjYtODwvc3R5bGU+PC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjk0NDwvcmVj

LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImQ5dmZ3dDlkNzB3d3dm

ZWFzMGRwdDl2bmYyemV0cHNzOWQ5ZCIgdGltZXN0YW1wPSIxNTAxMDMwODkxIj45NDQ8L2tleT48

L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1hdnJha2FuYXMsIFQuIEEuPC9hdXRo

b3I+PGF1dGhvcj5TYW1lciwgQy4gRi48L2F1dGhvcj48YXV0aG9yPk5lc3NpbSwgUy4gSi48L2F1

dGhvcj48YXV0aG9yPkZyaXNjaCwgRy48L2F1dGhvcj48YXV0aG9yPkxpcG1hbiwgTS4gTC48L2F1

dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EaXZpc2lvbiBvZiBO

ZXBocm9sb2d5LCBKZXdpc2ggR2VuZXJhbCBIb3NwaXRhbCwgTWNHaWxsIFVuaXZlcnNpdHksIE1v

bnRyZWFsLCBRdWViZWMsIENhbmFkYTsgYW5kIHRob21hcy5tYXZyYWthbmFzQG1haWwubWNnaWxs

LmNhLiYjeEQ7RGl2aXNpb24gb2YgR2VuZXJhbCBJbnRlcm5hbCBNZWRpY2luZSBhbmQuJiN4RDtE

ZXBhcnRtZW50IG9mIENsaW5pY2FsIFBoYXJtYWNvbG9neSBhbmQgVG94aWNvbG9neSwgR2VuZXZh

IFVuaXZlcnNpdHkgSG9zcGl0YWxzLCBHZW5ldmEsIFN3aXR6ZXJsYW5kLiYjeEQ7RGl2aXNpb24g

b2YgTmVwaHJvbG9neSwgSmV3aXNoIEdlbmVyYWwgSG9zcGl0YWwsIE1jR2lsbCBVbml2ZXJzaXR5

LCBNb250cmVhbCwgUXVlYmVjLCBDYW5hZGE7IGFuZC48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0

aXRsZT5BcGl4YWJhbiBQaGFybWFjb2tpbmV0aWNzIGF0IFN0ZWFkeSBTdGF0ZSBpbiBIZW1vZGlh

bHlzaXMgUGF0aWVudHM8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+SiBBbSBTb2MgTmVwaHJvbDwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiB0aGUgQW1lcmljYW4gU29jaWV0

eSBvZiBOZXBocm9sb2d5IDogSkFTTjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxm

dWxsLXRpdGxlPkogQW0gU29jIE5lcGhyb2w8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEFtIFNvYyBOZXBocm9sPC9mdWxsLXRpdGxlPjxhYmJy

LTE+Sm91cm5hbCBvZiB0aGUgQW1lcmljYW4gU29jaWV0eSBvZiBOZXBocm9sb2d5IDogSkFTTjwv

YWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjIyNDEtMjI0ODwvcGFnZXM+PHZvbHVtZT4y

ODwvdm9sdW1lPjxudW1iZXI+NzwvbnVtYmVyPjxlZGl0aW9uPjIwMTcvMDMvMTg8L2VkaXRpb24+

PGtleXdvcmRzPjxrZXl3b3JkPmFwaXhhYmFuPC9rZXl3b3JkPjxrZXl3b3JkPmF0cmlhbCBmaWJy

aWxsYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+aGVtb2RpYWx5c2lzPC9rZXl3b3JkPjxrZXl3b3Jk

PnBoYXJtYWNva2luZXRpY3M8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxNzwv

eWVhcj48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2Ju

PjEwNDYtNjY3MzwvaXNibj48YWNjZXNzaW9uLW51bT4yODMwMjc1NDwvYWNjZXNzaW9uLW51bT48

dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjE2ODEvYXNuLjIwMTYwOTA5

ODA8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN

PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv

cmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+TGVpbDwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl

Y051bT45Mjg8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjkyODwvcmVjLW51bWJlcj48Zm9y

ZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImQ5dmZ3dDlkNzB3d3dmZWFzMGRwdDl2bmYy

emV0cHNzOWQ5ZCIgdGltZXN0YW1wPSIxNTAwNTE3NDM4Ij45Mjg8L2tleT48L2ZvcmVpZ24ta2V5

cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1

dG9ycz48YXV0aG9ycz48YXV0aG9yPkxlaWwsIFQuIEEuPC9hdXRob3I+PGF1dGhvcj5GZW5nLCBZ

LjwvYXV0aG9yPjxhdXRob3I+WmhhbmcsIEwuPC9hdXRob3I+PGF1dGhvcj5QYWNjYWx5LCBBLjwv

YXV0aG9yPjxhdXRob3I+TW9oYW4sIFAuPC9hdXRob3I+PGF1dGhvcj5QZmlzdGVyLCBNLjwvYXV0

aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRpc2NvdmVyeSBNZWRp

Y2luZSBhbmQgQ2xpbmljYWwgUGhhcm1hY29sb2d5LCBCcmlzdG9sLU15ZXJzIFNxdWliYiwgTGF3

cmVuY2V2aWxsZSwgTmV3IEplcnNleSwgVVNBLiB0YXJlay5sZWlsQHBmaXplci5jb208L2F1dGgt

YWRkcmVzcz48dGl0bGVzPjx0aXRsZT5RdWFudGlmaWNhdGlvbiBvZiBhcGl4YWJhbiZhcG9zO3Mg

dGhlcmFwZXV0aWMgdXRpbGl0eSBpbiBwcmV2ZW50aW9uIG9mIHZlbm91cyB0aHJvbWJvZW1ib2xp

c206IHNlbGVjdGlvbiBvZiBwaGFzZSBJSUkgdHJpYWwgZG9zZTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5DbGluIFBoYXJtYWNvbCBUaGVyPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5DbGlu

aWNhbCBwaGFybWFjb2xvZ3kgYW5kIHRoZXJhcGV1dGljczwvYWx0LXRpdGxlPjwvdGl0bGVzPjxw

ZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUGhhcm1hY29sIFRoZXI8L2Z1bGwtdGl0bGU+PGFi

YnItMT5DbGluaWNhbCBwaGFybWFjb2xvZ3kgYW5kIHRoZXJhcGV1dGljczwvYWJici0xPjwvcGVy

aW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2xpbiBQaGFybWFjb2wgVGhlcjwv

ZnVsbC10aXRsZT48YWJici0xPkNsaW5pY2FsIHBoYXJtYWNvbG9neSBhbmQgdGhlcmFwZXV0aWNz

PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+Mzc1LTgyPC9wYWdlcz48dm9sdW1lPjg4

PC92b2x1bWU+PG51bWJlcj4zPC9udW1iZXI+PGVkaXRpb24+MjAxMC8wOC8wNjwvZWRpdGlvbj48

a2V5d29yZHM+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5BcmVhIFVuZGVyIEN1cnZl

PC9rZXl3b3JkPjxrZXl3b3JkPkNsaW5pY2FsIFRyaWFscywgUGhhc2UgSUkgYXMgVG9waWM8L2tl

eXdvcmQ+PGtleXdvcmQ+Q2xpbmljYWwgVHJpYWxzLCBQaGFzZSBJSUkgYXMgVG9waWMvbWV0aG9k

czwva2V5d29yZD48a2V5d29yZD5Db21wdXRlciBTaW11bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk

PkRvc2UtUmVzcG9uc2UgUmVsYXRpb25zaGlwLCBEcnVnPC9rZXl3b3JkPjxrZXl3b3JkPkVub3hh

cGFyaW4vYWRtaW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlL3BoYXJtYWNvbG9neTwva2V5d29yZD48

a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+Rmlicmlub2x5dGljIEFnZW50cy9hZG1p

bmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2UvYWR2ZXJzZSBlZmZlY3RzLypwaGFybWFjb2xvZ3k8L2tl

eXdvcmQ+PGtleXdvcmQ+SGVtb3JyaGFnZS8qY2hlbWljYWxseSBpbmR1Y2VkPC9rZXl3b3JkPjxr

ZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5LaWRuZXkgRGlzZWFzZXMvY29tcGxpY2F0

aW9uczwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPipNb2RlbHMsIEJp

b2xvZ2ljYWw8L2tleXdvcmQ+PGtleXdvcmQ+UHlyYXpvbGVzL2FkbWluaXN0cmF0aW9uICZhbXA7

IGRvc2FnZS9hZHZlcnNlIGVmZmVjdHMvKnBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5d29yZD5Q

eXJpZG9uZXMvYWRtaW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlL2FkdmVyc2UgZWZmZWN0cy8qcGhh

cm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlZlbm91cyBUaHJvbWJvZW1ib2xpc20vKnByZXZl

bnRpb24gJmFtcDsgY29udHJvbDwva2V5d29yZD48a2V5d29yZD5XYXJmYXJpbi9hZG1pbmlzdHJh

dGlvbiAmYW1wOyBkb3NhZ2UvcGhhcm1hY29sb2d5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVz

Pjx5ZWFyPjIwMTA8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5TZXA8L2RhdGU+PC9wdWItZGF0ZXM+

PC9kYXRlcz48aXNibj4wMDA5LTkyMzY8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjA2ODY0Nzc8L2Fj

Y2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDM4

L2NscHQuMjAxMC4xMDY8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2Ut

cHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFu

Z3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxSZWNOdW0+OTQ1PC9SZWNOdW0+PHJlY29yZD48

cmVjLW51bWJlcj45NDU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRi

LWlkPSJkOXZmd3Q5ZDcwd3d3ZmVhczBkcHQ5dm5mMnpldHBzczlkOWQiIHRpbWVzdGFtcD0iMTUw

MTAzMTY5NCI+OTQ1PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkdlbmVyaWMi

PjEzPC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRpdGxl

PlBmaXplciBDYW5hZGEgSW5jLiAmYW1wOyBCcmlzdG9sLU15ZXJzIFNxdWliYiBDYW5hZGEuIFBy

b2R1Y3QgTW9ub2dyYXBoLiBFbGlxdWlzICAgQXBpeGFiYW4gVGFibGV0cyAyLjUgbWcgYW5kIDUg

bWcgQW50aWNvYWd1bGFudDwvdGl0bGU+PC90aXRsZXM+PGRhdGVzPjx5ZWFyPjIwMTY8L3llYXI+

PC9kYXRlcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3dy5wZml6ZXIuY2Evc2l0

ZXMvZy9maWxlcy9nMTAwMjgxMjYvZi8yMDE2MDcvRUxJUVVJU18gUE1fMTg0NDY0XzE2SnVuZTIw

MTZfRV9tYXJrZXRlZC5wZGY8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGFjY2Vzcy1kYXRl

PjIwMTcvMDcvMjYvPC9hY2Nlc3MtZGF0ZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXZyYWthbmFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVh

cj48UmVjTnVtPjk0NDwvUmVjTnVtPjxEaXNwbGF5VGV4dD48c3R5bGUgZmFjZT0ic3VwZXJzY3Jp

cHQiPjYtODwvc3R5bGU+PC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjk0NDwvcmVj

LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImQ5dmZ3dDlkNzB3d3dm

ZWFzMGRwdDl2bmYyemV0cHNzOWQ5ZCIgdGltZXN0YW1wPSIxNTAxMDMwODkxIj45NDQ8L2tleT48

L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1hdnJha2FuYXMsIFQuIEEuPC9hdXRo

b3I+PGF1dGhvcj5TYW1lciwgQy4gRi48L2F1dGhvcj48YXV0aG9yPk5lc3NpbSwgUy4gSi48L2F1

dGhvcj48YXV0aG9yPkZyaXNjaCwgRy48L2F1dGhvcj48YXV0aG9yPkxpcG1hbiwgTS4gTC48L2F1

dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EaXZpc2lvbiBvZiBO

ZXBocm9sb2d5LCBKZXdpc2ggR2VuZXJhbCBIb3NwaXRhbCwgTWNHaWxsIFVuaXZlcnNpdHksIE1v

bnRyZWFsLCBRdWViZWMsIENhbmFkYTsgYW5kIHRob21hcy5tYXZyYWthbmFzQG1haWwubWNnaWxs

LmNhLiYjeEQ7RGl2aXNpb24gb2YgR2VuZXJhbCBJbnRlcm5hbCBNZWRpY2luZSBhbmQuJiN4RDtE

ZXBhcnRtZW50IG9mIENsaW5pY2FsIFBoYXJtYWNvbG9neSBhbmQgVG94aWNvbG9neSwgR2VuZXZh

IFVuaXZlcnNpdHkgSG9zcGl0YWxzLCBHZW5ldmEsIFN3aXR6ZXJsYW5kLiYjeEQ7RGl2aXNpb24g

b2YgTmVwaHJvbG9neSwgSmV3aXNoIEdlbmVyYWwgSG9zcGl0YWwsIE1jR2lsbCBVbml2ZXJzaXR5

LCBNb250cmVhbCwgUXVlYmVjLCBDYW5hZGE7IGFuZC48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0

aXRsZT5BcGl4YWJhbiBQaGFybWFjb2tpbmV0aWNzIGF0IFN0ZWFkeSBTdGF0ZSBpbiBIZW1vZGlh

bHlzaXMgUGF0aWVudHM8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+SiBBbSBTb2MgTmVwaHJvbDwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiB0aGUgQW1lcmljYW4gU29jaWV0

eSBvZiBOZXBocm9sb2d5IDogSkFTTjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxm

dWxsLXRpdGxlPkogQW0gU29jIE5lcGhyb2w8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEFtIFNvYyBOZXBocm9sPC9mdWxsLXRpdGxlPjxhYmJy

LTE+Sm91cm5hbCBvZiB0aGUgQW1lcmljYW4gU29jaWV0eSBvZiBOZXBocm9sb2d5IDogSkFTTjwv

YWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjIyNDEtMjI0ODwvcGFnZXM+PHZvbHVtZT4y

ODwvdm9sdW1lPjxudW1iZXI+NzwvbnVtYmVyPjxlZGl0aW9uPjIwMTcvMDMvMTg8L2VkaXRpb24+

PGtleXdvcmRzPjxrZXl3b3JkPmFwaXhhYmFuPC9rZXl3b3JkPjxrZXl3b3JkPmF0cmlhbCBmaWJy

aWxsYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+aGVtb2RpYWx5c2lzPC9rZXl3b3JkPjxrZXl3b3Jk

PnBoYXJtYWNva2luZXRpY3M8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxNzwv

eWVhcj48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2Ju

PjEwNDYtNjY3MzwvaXNibj48YWNjZXNzaW9uLW51bT4yODMwMjc1NDwvYWNjZXNzaW9uLW51bT48

dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjE2ODEvYXNuLjIwMTYwOTA5

ODA8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxN

PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv

cmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+TGVpbDwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl

Y051bT45Mjg8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjkyODwvcmVjLW51bWJlcj48Zm9y

ZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImQ5dmZ3dDlkNzB3d3dmZWFzMGRwdDl2bmYy

emV0cHNzOWQ5ZCIgdGltZXN0YW1wPSIxNTAwNTE3NDM4Ij45Mjg8L2tleT48L2ZvcmVpZ24ta2V5

cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1

dG9ycz48YXV0aG9ycz48YXV0aG9yPkxlaWwsIFQuIEEuPC9hdXRob3I+PGF1dGhvcj5GZW5nLCBZ

LjwvYXV0aG9yPjxhdXRob3I+WmhhbmcsIEwuPC9hdXRob3I+PGF1dGhvcj5QYWNjYWx5LCBBLjwv

YXV0aG9yPjxhdXRob3I+TW9oYW4sIFAuPC9hdXRob3I+PGF1dGhvcj5QZmlzdGVyLCBNLjwvYXV0

aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRpc2NvdmVyeSBNZWRp

Y2luZSBhbmQgQ2xpbmljYWwgUGhhcm1hY29sb2d5LCBCcmlzdG9sLU15ZXJzIFNxdWliYiwgTGF3

cmVuY2V2aWxsZSwgTmV3IEplcnNleSwgVVNBLiB0YXJlay5sZWlsQHBmaXplci5jb208L2F1dGgt

YWRkcmVzcz48dGl0bGVzPjx0aXRsZT5RdWFudGlmaWNhdGlvbiBvZiBhcGl4YWJhbiZhcG9zO3Mg

dGhlcmFwZXV0aWMgdXRpbGl0eSBpbiBwcmV2ZW50aW9uIG9mIHZlbm91cyB0aHJvbWJvZW1ib2xp

c206IHNlbGVjdGlvbiBvZiBwaGFzZSBJSUkgdHJpYWwgZG9zZTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5DbGluIFBoYXJtYWNvbCBUaGVyPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5DbGlu

aWNhbCBwaGFybWFjb2xvZ3kgYW5kIHRoZXJhcGV1dGljczwvYWx0LXRpdGxlPjwvdGl0bGVzPjxw

ZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUGhhcm1hY29sIFRoZXI8L2Z1bGwtdGl0bGU+PGFi

YnItMT5DbGluaWNhbCBwaGFybWFjb2xvZ3kgYW5kIHRoZXJhcGV1dGljczwvYWJici0xPjwvcGVy

aW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2xpbiBQaGFybWFjb2wgVGhlcjwv

ZnVsbC10aXRsZT48YWJici0xPkNsaW5pY2FsIHBoYXJtYWNvbG9neSBhbmQgdGhlcmFwZXV0aWNz

PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+Mzc1LTgyPC9wYWdlcz48dm9sdW1lPjg4

PC92b2x1bWU+PG51bWJlcj4zPC9udW1iZXI+PGVkaXRpb24+MjAxMC8wOC8wNjwvZWRpdGlvbj48

a2V5d29yZHM+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5BcmVhIFVuZGVyIEN1cnZl

PC9rZXl3b3JkPjxrZXl3b3JkPkNsaW5pY2FsIFRyaWFscywgUGhhc2UgSUkgYXMgVG9waWM8L2tl

eXdvcmQ+PGtleXdvcmQ+Q2xpbmljYWwgVHJpYWxzLCBQaGFzZSBJSUkgYXMgVG9waWMvbWV0aG9k

czwva2V5d29yZD48a2V5d29yZD5Db21wdXRlciBTaW11bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3Jk

PkRvc2UtUmVzcG9uc2UgUmVsYXRpb25zaGlwLCBEcnVnPC9rZXl3b3JkPjxrZXl3b3JkPkVub3hh

cGFyaW4vYWRtaW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlL3BoYXJtYWNvbG9neTwva2V5d29yZD48

a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+Rmlicmlub2x5dGljIEFnZW50cy9hZG1p

bmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2UvYWR2ZXJzZSBlZmZlY3RzLypwaGFybWFjb2xvZ3k8L2tl

eXdvcmQ+PGtleXdvcmQ+SGVtb3JyaGFnZS8qY2hlbWljYWxseSBpbmR1Y2VkPC9rZXl3b3JkPjxr

ZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5LaWRuZXkgRGlzZWFzZXMvY29tcGxpY2F0

aW9uczwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPipNb2RlbHMsIEJp

b2xvZ2ljYWw8L2tleXdvcmQ+PGtleXdvcmQ+UHlyYXpvbGVzL2FkbWluaXN0cmF0aW9uICZhbXA7

IGRvc2FnZS9hZHZlcnNlIGVmZmVjdHMvKnBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5d29yZD5Q

eXJpZG9uZXMvYWRtaW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlL2FkdmVyc2UgZWZmZWN0cy8qcGhh

cm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlZlbm91cyBUaHJvbWJvZW1ib2xpc20vKnByZXZl

bnRpb24gJmFtcDsgY29udHJvbDwva2V5d29yZD48a2V5d29yZD5XYXJmYXJpbi9hZG1pbmlzdHJh

dGlvbiAmYW1wOyBkb3NhZ2UvcGhhcm1hY29sb2d5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVz

Pjx5ZWFyPjIwMTA8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5TZXA8L2RhdGU+PC9wdWItZGF0ZXM+

PC9kYXRlcz48aXNibj4wMDA5LTkyMzY8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjA2ODY0Nzc8L2Fj

Y2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDM4

L2NscHQuMjAxMC4xMDY8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2Ut

cHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFu

Z3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxSZWNOdW0+OTQ1PC9SZWNOdW0+PHJlY29yZD48

cmVjLW51bWJlcj45NDU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRi

LWlkPSJkOXZmd3Q5ZDcwd3d3ZmVhczBkcHQ5dm5mMnpldHBzczlkOWQiIHRpbWVzdGFtcD0iMTUw

MTAzMTY5NCI+OTQ1PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkdlbmVyaWMi

PjEzPC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRpdGxl

PlBmaXplciBDYW5hZGEgSW5jLiAmYW1wOyBCcmlzdG9sLU15ZXJzIFNxdWliYiBDYW5hZGEuIFBy

b2R1Y3QgTW9ub2dyYXBoLiBFbGlxdWlzICAgQXBpeGFiYW4gVGFibGV0cyAyLjUgbWcgYW5kIDUg

bWcgQW50aWNvYWd1bGFudDwvdGl0bGU+PC90aXRsZXM+PGRhdGVzPjx5ZWFyPjIwMTY8L3llYXI+

PC9kYXRlcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3dy5wZml6ZXIuY2Evc2l0

ZXMvZy9maWxlcy9nMTAwMjgxMjYvZi8yMDE2MDcvRUxJUVVJU18gUE1fMTg0NDY0XzE2SnVuZTIw

MTZfRV9tYXJrZXRlZC5wZGY8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGFjY2Vzcy1kYXRl

PjIwMTcvMDcvMjYvPC9hY2Nlc3MtZGF0ZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA 6-8 Target apixaban trough levels appear to be a median of 80 to 100ng/mL for atrial fibrillation (95% range 41 to 230 ng/mL) and 63 (95% range 22 to 167) for VTE. Apixaban is not removed by haemodialysis. ADDIN EN.CITE <EndNote><Cite><Author>Wang</Author><Year>2016</Year><RecNum>877</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>877</rec-number><foreign-keys><key app="EN" db-id="d9vfwt9d70wwwfeas0dpt9vnf2zetpss9d9d" timestamp="1479791140">877</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wang, Xiaoli</author><author>Tirucherai, Giridhar</author><author>Marbury, Thomas C.</author><author>Wang, Jessie</author><author>Chang, Ming</author><author>Zhang, Donglu</author><author>Song, Yan</author><author>Pursley, Janice</author><author>Boyd, Rebecca A.</author><author>Frost, Charles</author></authors></contributors><titles><title>Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis</title><secondary-title>The Journal of Clinical Pharmacology</secondary-title></titles><periodical><full-title>The Journal of Clinical Pharmacology</full-title></periodical><pages>628-636</pages><volume>56</volume><keywords><keyword>apixaban</keyword><keyword>end-stage renal disease</keyword><keyword>hemodialysis</keyword><keyword>pharmacodynamics</keyword><keyword>pharmacokinetics</keyword></keywords><dates><year>2016</year><pub-dates><date>May 1, 2016</date></pub-dates></dates><isbn>1552-4604</isbn><urls></urls><electronic-resource-num>10.1002/jcph.628</electronic-resource-num><remote-database-name>Wiley Online Library</remote-database-name><language>en</language><access-date>2016-11-08 04:26:47</access-date></record></Cite></EndNote>9Key ObjectiveTo provide Canberra Hospital and Health Services (CHHS) staff with information regarding the administration of apixaban to patients with severe chronic kidney disease.Alerts Apixaban increases the risk and severity of bleeding.Concurrent use of medication that is strong inhibitors or inducers of CYP3A4 since these will affect the intensity of apixaban on the clotting system.Current use of apixaban is a contraindication to transplantation. It should not generally be used in patients active on the deceased donor renal transplant waiting list.Back to Table of ContentsScopeThis Clinical Guideline applies to medical staff of Canberra Hospital Health Service (CHHS).Prescription of apixaban to patients with estimated creatinine clearance <25mL/min must occur only with the express permission of a renal physician and after the patient has provided informed consent for use. Clinicians prescribing apixaban are to ensure patients receive appropriate counselling (see attachment).Back to Table of ContentsSection 1 – Apixaban Target Trough Levels and DosageThe target trough level 50 to 200ng/mL when measured at ACT Pathology.IndicationPatient GroupApixaban Initial Dose (for 7 days)Subsequent Apixaban DoseApixaban Dose after 6 monthsMeasure trough anti-Xa levels*Non-massive venous thromboembolismNon-dialysis 10mg bd5 mg bd2.5mg bd7 days, 14 days then every 3 monthsNon-massive venous thromboembolismDialysisand non-dialysis 10mg bd2.5 mg bd2.5mg bd7 days, 14 days then every 3 monthsNon valvular Atrial fibrillation Dialysis and non-dialysis with, age ≥80 years or body weight ≤60 kg2.5 mg bd2.5 mg bd2.5 mg bd7 days then every 3 monthsNon valvular Atrial fibrillation Non-dialysis with, age <80 years and body weight >60 kg5 mg bd5 mg bd5 mg bd7 days then every 3 monthsApixaban trough levels are based on measurement immediately prior to dosing on a 12 hour dosing regimen. The pathology request form must specify “anti-Xa level (apixaban).”Current American Food and Drug Administration advice is not to alter the apixaban dose in patients on dialysis. The above table takes into account more recent information (discussed in the Background above)Apixaban concentration is affected by strong inducers and inhibitors of CYP3A4Exercise clinical judgment regarding dosing in the very elderly (age >80 years) and very small patients (<45 kg). Back to Table of Contents Section 2 – Planned Elective Surgery Patients taking apixaban who require elective surgery should not take the apixaban for 48 – 72 hours prior to the surgery. The anticoagulant effect will usually be negligible after withholding apixaban for 48-72 hours or if the anti-Xa activity (apixaban) is <20 U/mL. Depending on the perceived risk of clotting and bleeding, withholding apixaban for up to 5 days prior to procedure may be appropriate. The use of bridging doses of heparin should be considered on a case by case basis, taking into account the risk of bleeding and of thrombosis.Back to Table of Contents Section 3 – Haemorrhage In the event of clinically significant active bleeding take a sample of the patient’s blood from either a vein or artery as seems most clinically appropriate at the time. The sample may be taken from a peripheral or central blood sampling device and should be sent for coagulation studies including anti-Xa activity (apixaban). Give the patient a systemic dose of prothrombinex 30-50units/kg ideal body weight. After the administration of prothrombinex in some circumstances a second sample may be taken for the purposes of quality assurance. This should not be used for acute management of the patient. The sample may be taken from a peripheral or central blood sampling device (as seems most clinically appropriate at the time) and should be sent for coagulation studies including anti-Xa activity (apixaban). The sample should not be sent earlier than 20 minutes after completion of the prothrombinex infusion or more than 2 hours after. Note: prothrombinex does not reduce the concentration of apixaban and normalisation of the prothrombin time does not indicate the absence of anti-Xa effect. For this reason local haemostatic measures are essential whenever possible. Local haemostatic measures include local pressure (such as with use of finger, hand or sandbag to the area, use of a tourniquet or inflation of a blood pressure cuff above systolic blood pressure), closure of any actively bleeding vessels through endoscopic, angiographic or surgical techniques.Use of intravenous desmopressin (DDAVP), 0.3 mcg/kg, may help reduce bleeding for those taking antiplatelet agents and those with possible uraemic bleeding.Back to Table of Contents Implementation Following approval of this Guideline an education session will be provided to renal unit doctors. The clinical guideline will be available to all staff on the policy register. It will be communicated to affected staff via team meetings.Back to Table of ContentsRelated Policies, Procedures, Guidelines and LegislationPoliciesConsent and TreatmentPatient Identification and Procedure Matching Policy ProceduresPatient Identification and Procedure Matching ProcedurePatient Identification – Pathology Specimen Labelling Procedure LegislationHealth Records (Privacy and Access) Act 1997Human Rights Act 2004Back to Table of ContentsReferences ADDIN EN.REFLIST 1Van Der Meersch H, De Bacquer D, De Vriese AS. Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: A systematic review and meta-analysis. American Heart Journal. 2017; 184: 37-46.2Tanner NC, Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database of Systematic Reviews. 2015.3Brandenburg VM, Kramann R, Rothe H, Kaesler N, Korbiel J, Specht P, et al. Calcific uraemic arteriolopathy (calciphylaxis): data from a large nationwide registry. Nephrol Dial Transplant. 2017; 32: 126-32.4FDA Apixaban Labelling. Vol. 2017.5Chan KE, Giugliano RP, Patel MR, Abramson S, Jardine M, Zhao S, et al. Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF. J Am Coll Cardiol. 2016; 67: 2888-99.6Mavrakanas TA, Samer CF, Nessim SJ, Frisch G, Lipman ML. Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients. J Am Soc Nephrol. 2017; 28: 2241-48.7Leil TA, Feng Y, Zhang L, Paccaly A, Mohan P, Pfister M. Quantification of apixaban's therapeutic utility in prevention of venous thromboembolism: selection of phase III trial dose. Clinical pharmacology and therapeutics. 2010; 88: 375-82.8Pfizer Canada Inc. & Bristol-Myers Squibb Canada. Product Monograph. Eliquis Apixaban Tablets 2.5 mg and 5 mg Anticoagulant. 2016.9Wang X, Tirucherai G, Marbury TC, Wang J, Chang M, Zhang D, et al. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. The Journal of Clinical Pharmacology. 2016; 56: 628-36.Back to Table of ContentsDefinition of Terms NOAC: Novel oral anticoagulant.CKD: Chronic kidney failureBd: twice a dayCYP3A4: Cytochrome P-450 subtype 3A4Ideal body weight in kg: is 22 multiplied by the square of the patient’s height in meters. (height2 x 22)ng: NanogramBack to Table of ContentsSearch Terms Apixaban, anticoagulant, dialysis, chronic kidney disease AttachmentsAttachment 1 – Apixaban Clinician Discussion Points Disclaimer: This document has been developed by ACT Health, Canberra Hospital and Health Services specifically for its own use. Use of this document and any reliance on the information contained therein by any third party is at his or her own risk and Health Directorate assumes no responsibility whatsoever.Policy Team ONLY to complete the following:Date AmendedSection AmendedDivisional ApprovalFinal Approval 25/05/2018New Document Girish Talulikar, ED, MedicineCHHS Policy Committee This document supersedes the following: Document NumberDocument NameAttachment 1 – Apixaban Clinician Discussion Points Apixaban (Eliquis) checklist of information to be conveyed to patients with severe kidney failure prior to obtaining informed consent. Apixaban is a drug that reduces blood clotting. It is licensed for use in Australia for patients at risk of blood clots from atrial fibrillation (an irregular heart beat) and for patients that have had a clot in a deep vein (DVT) or lungs (PE). It can also be used to prevent clots in your veins after a hip or knee replacement surgery.Apixaban is not licensed for use in people with severe kidney failure in Australia. This is because there is limited information available on its use in this patient group. Drugs are sometimes prescribed for unlicensed (“off label”) use by doctors and when this occurs informed consent from the patient is important.All medications that reduce blood clotting, including apixaban, can increase the risk of bleeding. The bleeding can be minor resulting in things such as bruising or more severe and potentially life threatening. We do not know if this risk is greater for patients with severe kidney disease.An alternative to apixaban may be warfarin, which also reduces the risk of blood clots but can also increase the risk of bleeding. Unlike apixaban, warfarin has numerous food and drug interactions, and the need for regular monitoring and dose adjustments can be difficult for patients. In addition, the variable levels of warfarin in the blood may result in the blood being either over or under anticoagulated some of the time potentially making it less effective. There is also very limited or consistent data for the effectiveness or risks of warfarin in patients with severe kidney failure. Apixaban has a relatively consistent anticoagulant effect so a particular dose usually leads to the desired level of anticoagulation – neither too much, nor too little. It is not affected by changes in diet and is affected by only a limited number of other medications. Information is available on how kidney function or dialysis affects the levels of apixaban in the blood so we are able to determine what dose is likely to give the same blood levels seen in healthy people taking the recommended dose without kidney disease.The effects of warfarin can be reversed with vitamin K. Vitamin K is an antidote to warfarin. This reversal is not immediate, but if severe bleeding occurs, it can often be reduced within a few hours. Currently apixaban effects cannot be reliably reversed and there is no antidote. The anticoagulant effect usually wears off within 2 days of stopping the medication. If severe bleeding occurs measures can be taken to control this. ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download