DOACs and Warfarin

Question 1

what does apixaban inhibit

Answer 1

direct inhibitor of FXa

Question 2

mechanism of action of Apixaban

Answer 2

potent oral reversible direct and selective active site inhibitor of FXa

inhibits free and clot bound FXa and prothrombinase activity

Question 3

what effect does Apixaban have on platelet aggregation

Answer 3

has no direct effect - indirectly inhibits aggregation induced by thrombin

prevents thrombin generation and thrombus development

Question 4

dosing of Apixaban

Answer 4

10mg BD for 7 days

then 5mg BD for duration of treatment

Question 5

when is dose reduction available for Apixaban

Answer 5

two of the following:

• > 80
• <60kg
• creatinine >133

Question 6

true or false: dabigatran is a prodrug

Answer 6

true - it is a prodrug with no activity

Question 7

mechanism of action of Dabigatran

Answer 7

competitive reversible direct thrombin inhibitor

following oral administration, dabigatran etexilate is rapidly absorbed and converted to active dabigatran by esterase catalysed hydrolysis in the liver and plasma

Question 8

what does thrombin enable the conversion of

Answer 8

fibrinogen to fibrin during the coagulation cascade

therefore thrombin inhibition prevents the development of a thrombus

Question 9

dosing of dabigatran

Answer 9

150mg BD following 5 days of parenteral therapy

Question 10

when is dose reduction available on dabigatran

Answer 10

available to 110mg BD for those >80 years or also on verapamil

Question 11

edoxaban mode of action

Answer 11

direct inhibitor of FXa

inhibits free FXa and prothrombinase activity

prevents thrombin generation and thrombus development

Question 12

dosing of edoxaban

Answer 12

60mg OD following 5 days of parenteral therapy

Question 13

when is dose reduction available on Edoxaban

Answer 13

dose reduction available to 30 mg OD when 1 or more of these are true:

• renal function between 15 and 50 ml/min
• <60kg
• use of certain medications such as erythromycin and cetoconazol

Question 14

mode of action of rivaroxaban

Answer 14

direct inhibitor of FXa

prevents thrombus development in the same way as apixaban and edoxaban

Question 15

dosing of rivaroxaban

Answer 15

15mg BD for 3 weeks then 20mg OD

Question 16

when is dose reduction of rivaroxaban available

Answer 16

considered reduction to 15mg OD if clinical risk of bleeding and poor renal function is high

Question 17

mode of action of warfarin

Answer 17

inhibits synthesis of vitamin K

Question 18

mode of action of warfarin

Answer 18

inhibits synthesis of vitamin k dependent clotting factors

e.g F11, FV11, FIX, FX, protein C and protein S

Question 19

dosing of warfarin

Answer 19

individualised to maintain target INR for that patient

Question 20

diagram of mechanism of action of drugs

Answer 20

Question 21

what is Option A

Answer 21

daily subcutaneous injections of low molecular weight heparin (LMWH) and to start on oral warfarin therapy at the same time

Question 22

requirements for Option A

Answer 22

• need to see if patient is willing to inject themselves and show them how and confirm technique
• includes provision of a yellow book

Question 23

what makes option A. a burden on working people

Answer 23

regular INR tests are required

Question 24

main side effect of option A

Answer 24

heavy bleeding

Question 25

what happens if you miss a dose of Option A

Answer 25

• if dose is missed before midnight, it should still be taken
• if does is missed after midnight then the dose should not be caught up - patient should tell the clinician of a missed dose at next INR checkup

Question 26

what can increase INR value

Answer 26

alcohol intake

Question 27

what is included in option B

Answer 27

direct oral anticoagulant therapy (DOAC)

Question 28

how is medication of DOACs started

Answer 28

some require 5 days of parenteral therapy before initiation - tablets started after 5 days of injections, not at the same time

Question 29

what happens if rivaroxaban is taken

Answer 29

4 week initiation pack is commercially available to facilitate the change from 15mg BD to 20mg OD

Question 30

what happens if there’s a missed dose of dabigatran

Answer 30

if remembered within 6 hours it should be taken, not If after the 6 hours

Question 31

what medications can be crushed up for use with feeding tubes and go in blister packs of required

Answer 31

apixaban
edoxiban
rivarocxaban

Question 32

what happens if warfarin is given via feeding tube

Answer 32

enteral feeds required 2 hours before and after each dose - due to vitamin K content of feeds.

Question 33

what medications are considered safer than warfarin

Answer 33

apixaban and edoxaban

Question 34

benefits of DOACs

Answer 34

not known to have many interactions with food drink or alcohol

Question 35

what is praxbind

Answer 35

is an IV infusion to be given if there is emergency surgery requirement of life threatening uncontrolled bleeding - it is a humanised monoclonal antibody that neutralises its anticoagulant effect but is very expensive

Question 36

what interact with Warfarin

Answer 36

clarithromycin and ibuprofen

Question 37

commercially available reversal agent for dabigatran

Answer 37

praxbind

Question 38

commercially available reversal agent for apixaban and rivaroxaban

Answer 38

ondexxya

Question 39

which drug does not have an available reversal agent

Answer 39

edoxaban