Venous Thromboembolism Therapeutics Lecture 2 Flashcards
1
Q
DOACs were first approved in Canada in what year?
A
2008
2
Q
which DOAC was the first to be approved in Canada?
A
Dabigatran
3
Q
DOACs have a _____ response with fixed dosing
A
predictable
4
Q
is anticoagulant monitoring required for DOACs?
A
no
5
Q
t/f DOACs have fewer drug and food interactions than warfarin
A
t
6
Q
what is the brand name of dabigatran?
A
Pradaxa
7
Q
which of the DOACs is a pro-drug?
A
dabigatran
8
Q
how is dabigatran etexilate changed into the active drug?
A
by esterase-catalysed hydrolysis in plasma and in the liver
9
Q
Dabigatran is a ____ (competitive vs non-competitive) reversible direct ___ inhibitor
A
competitive; thrombin
10
Q
what are the 3 indications for dabigatran?
A
- prevention of VTE in patients who had THR or TKR surgery
- treatment for VTE and prevention of recurrent VTE
- prevention of stroke and systemic embolism in patients with a fib
11
Q
what is the dosing of dabigatran for a VTE?
A
150mg po bid after 5-10 days of LMWH
12
Q
what is the dosing of dabigatran for extended VTE treatment?
A
150mg po bid
13
Q
what is the dosing of pradaxa for A fib?
A
110 or 150mg po bid (consider 110mg if age >80 or >75 with bleeding risk)
14
Q
What dose of pradaxa is used for knee/hip surgery?
A
110mg po once, then 220mg po daily (rarely used)
15
Q
what are key counselling points for Pradaxa (Dabigatran)
A
it contains acids to help in its absorption and this may cause dyspepsia, but you should not not antacids, but you can take with food and this often resolves. It must be stored in the blister
16
Q
what is the antidote for pradaxa?
A
idarucizumab (Praxbind)
17
Q
what is idarucizumab?
A
reversal agent specific to dabigatran; it is a monoclonal antibody
18
Q
what is the dose of idarucizumab to reverse dabigatran?
A
2 x 2.5g IV doses at a max of 15 min apart
19
Q
how long does it take for idarucizumab to reverse anticoagulant effect?
A
minutes
20
Q
what is an ADR of idarucizumab?
A
potential thrombosis
21
Q
use of idarucizumab is restricted to what situations?
A
life-threatening bleeding and emergency surgeries
22
Q
what is Rivaroxaban?
A
a highly selective, direct, antithrombin independent factor Xa inhibitor with high oral bioavailability
23
Q
how do selective Xa inhibitors like rivaroxaban work?
A
stop the amplified burst of thrombin generation, thereby diminishing thrombin-mediated activation of coagulation
24
Q
what are the 3 typical indications for Rivaroxaban?
A
- prevention of VTE in pts who have had TKR or THR
- treatment of DVT, PE and prevention of recurrent DVT and PE
- prevention of stroke and systemic embolism in patients with A fib in whom anticoagulation is appropriate
25
what are 2 newer indiactions for Rivaroxaban?
1. prevention of stroke, MI, and cardiovascular death, and for the prevention of acute limb ischemia and mortality in patients with CAD with or without peripheral artery disease
2. prevention of atherothrombotic events in patients with symptomatic PAD
26
dosing of xarelto for VTE
15mg po BID for 21 days. then 20mg po daily
27
what is the dosing of xarelto in extended VTE treatment?
10-20mg po daily
28
what is the xarelto dose in a fib?
20mg po uid
29
what is the xarelto dose in A fib if CrCl <50mL/min?
15mg po uid
30
xarelto dose for hip/knee surgery
10mg po daily for 14-35 days
31
xarelto dose for prophylaxis in medical patients
10mg po UID
32
xarelto dose for peripheral artery disease and CAD
2.5mg po BID with ASA 81mg daily
33
what is a special administration consultation point for xarelto?
the 20mg & 15mg tablets need to be taken with food to increase absorption
34
can xarelto tablets be crushed?
yes
35
what can be done if you miss a dose of xarelto?
if taking 15mg BID, you can double up at second dose, but do not double up in other situations
36
what is the antidote for xarelto?
andexanet alpha
37
what is the new formulation of xarelto? In what patient population is it used in?
granules for dispersion; peds
38
t/f there is evidence that xarelto can reduce hospitalization time
true
39
what is the drug class of abixaban?
direct Xa inhibitor
40
what are the 3 indications for abixaban?
1. prevention of VTE in adult patients who have undergone TKR or THR
2. prevention of stroke and systemic embolism in patients with A fib
3. treatment of VTE and prevention of recurrent DVT and PE
41
what is the name brand for apixaban?
eliquis
42
apixaban dosing for VTE treatment
10mg po BID for 7 days, then 5 mg po bid
43
what is dosage for extended treatment of VTE with apixaban?
2.5-5mg po bid
44
abixaban dosage for A fib
5mg po bid
45
what is the abixaban dosing for A fib if they have 2/3: age >80, weight <60kg, SCr >133`
2.5mg po bid
46
t/f there is a little evidence for the use of apixaban in end stage renal disease, and is sometimes used even in dialysis
t
47
apixaban dosage for hip/knee prophylaxis
2.5mg po bid
48
does apixaban need to be taken with food?
can be with or without
49
can apixaban be crushed?
yes
50
what can be done if patient misses a dose of apixaban?
can double up only if on 10mg po BID
51
what is the antidote for apixaban?
andexanet alpha
52
what are the Canadian and USA brand names for edoxaban?
lixiana and savaysa
53
what drug class is edoxaban?
direct factor Xa inhibitor
54
what are the 2 main indications for edoxaban?
1. prevention of stroke & systemic embolic events in patients with A Fib
2. treatment of VTE and the prevention of recurrent DVT and PE
55
what indication of edoxaban's "claim to fame"?
cancer associated thrombosis treatment
56
edoxaban dosage for VTE
60mg po uid following 5-10 days of LMWH treatment
57
what is the dosing of edoxaban for A fib?
60mg po uid
58
for both VTE and A fib treatment with edoxaban, what is the dose adjustment if CrCl is 30-50ml/min, age over 80 or PGP interactions?
30mg po uid
59
what is a benefit of edoxaban?
less prone to drug interactions
60
what is the antidote for edoxaban?
andexanet alfa
61
when on an anticoagulant, you may consider starting a ___ in some patients to reduce GI bleeding
PPI
62
list some drugs that affect hemostasis and would interact with anticoagulants
1. asprin and other antiplatelet agents
2. SSRIs
3. SNRIs
4. NSAIDs when used chronically
5. fibrinolytics
63
what does ASH recommend if patients require administration of inhibitors or inducers of PGP or strong inhibitors or inducers of CYP enzymes?
alternative anticoagulants like VKA or LMWH (not DOACs)
64
DOAC ____ is mediated by PGP
absorption
65
CYP3A4 enzymes are involved in the metabolism of what class of DOAC?
Xa inhibitors (not dabigatran)
66
give 3 examples of PGP inducers that would lower DOAC concentrations
carbamazepine, phenytoin, barbiturates
67
give 3 examples of CYP3A4 inducers that would lower DOAC levels
carbamazepine, phenytoin, barbiturates
68
andexanet alpha is the reversal agent for ____, but can be used for ___ as well
oral Xa inhibitors; LMWH and fondaparinux
69
what is the MOA of andexanet alfa?
it is just recombinant factor Xa, so it replaces the Xa inhibited by Xa inhibitors
70
how long does it take for andexanet alfa to reverse the effects of Xa inhibitors?
2 minutes
71
what is an ADR of andexanet alfa?
thrombosis
72
will PTT be higher or lower if the patient has HIT?
will be higher (bc there are fewer platelets to form a clot and it will take longer)
73
if there is a minimal change in PTT for dabigatran or edoxaban therapy does it mean the therapy is not working?
no, these drugs do not have a major effect on this lab value
74
which drugs give the most noticable increase in PTT?
UFH, argatroban and dabigatran (direct thrombin inhibitors)
75
heparin treatment should be limited to ____days to reduce risk for HIT (if possible)
5
76
you should avoid using heparin within ____days of previous heparin use
100
77
UFH should be stopped ___hrs before surgery
4-6
78
LMWH should be stopped ___hrs before surgery
24
79
if patient has normal renal function and is scheduled for a low bleeding risk procedure, when should their dabigatran be stopped?
24 hrs before
80
if a patient has normal renal function and is scheduled for a high bleeding risk procedure, when should their dabigatran be stopped?
48 hrs before
81
if a patient has eGFR of 50-79 and is scheduled for a low bleeding risk procedure, when should you stop their dabigatran?
24-48 hrs beofre
82
if a patient has eGFR of 50-79 and is scheduled for a high bleeding risk procedure, when should you stop their dabigatran?
48-72 hrs before
83
if a patient has a eGFR of 30-49 and low bleeding risk procedure, when should you stop their dabigatran?
48-72 hrs before
84
is a patient has a eGFR of 30-49 and scheduled for a high bleeding risk procedure, when should you stop their dabigatran?
96hrs before
85
dabigatran should not be used if eGFR is below ___ml/min
30
86
if a patient has eGFR of 30+ and is scheduled for a low bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?
24 hrs before
87
if a patient has a eGFR of 30+ and is scheduled for a high bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?
48hrs before
88
is a patient has a eGFR of 15-29 and is scheduled for. low bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?
48hrs before
89
if a patient has a eGFR of 15-29 and is scheduled for a high bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?
72 hrs before
90
warfarin should be stopped how long before surgery?
5 dyas before and INR needs to be checked the morning of surgery
91
how long should fondaparinux be stopped before surgery?
36-42 hrs before
92
if an IV bolus of heparin was given less than 1 hr ago, how much protamine is needed to reverse?
1mg/100u of heparin
93
if an IV bolus of heparin was given 1-2 hours ago, how much protamine is required to reverse?
1mg/200u of heparin
94
if a bolus of heparin was given more than 2 hrs ago, how much protamine is needed to reverse?
1mg/400U of heparin
95
if an IV infusion of heparin was given within the past 2 hrs, what dose of protamine should be given to reverse?
1mg/100u heparin
96
Px dose of rivaroxaban for TKRor THR?
10mg PO uid
97
Px dose of apixaban of TKR or THR?
2.5mg UID
98
px dose of dabigatran for TKR or THR?
220mg PO uid
99
px dose of enoxaparin for TKR or THR?
30mg SC BID or 40mg UID
100
px dose of dalteparin for TKR or THR
5000 U SQ uid
101
Px dose of tinzaparin for THR or TKR?
4500 U or 75U/kg SQ uid
102
Px dose of fondaparinux for THR or TKR?
2.5mg SQ uid
103
duration of Px therapy for TKR or THR
14-35 days
104
Px dose of enoxaparin for hip fracture surgery
30-40mg sq uid
105
Px dose of dalteparin for hip fracture surgery
2500 or 5000U SQ uid
106
Px dose of tinzaparin for hip fracture surgery
4500U sq uid
107
Px dose of fondaparinux for hip fracture surgery
2.5mg SQ UID
108
Px duration for hip fracture surgery
14-35 days
109
what lab values should be checked before surgery?
INR, PT, PTT
110
how long does it take for idarucizumab to reverse dabigatran?
less than 5 min
111
dose of andexanet alfa to reverse DOACs, fondapariux, and enoxaparin
IV bolus 400/800mg; continuous infusion 4-8mg/min up to 120 min
112
what lab test is used to test the efficacy of rivaroxaban?
anti Xa assay
113
what are some advantages of DOACs over warafarin?
1. does not require as much monitoring
2. rivaroxaban may have lower risk of cerebral hemmorhage
3. predictable response with fixed dosing
4. fewer drug interactions
5. can be switched more readily
114
what are some advantages of warfarin over DOACs?
1. cheaper
| 2. have been around longer, more research
