Transcript Power Point presentatie versie Office 2003

AZ. ST. JANSCOLLOQUIA FLASHAVOND ETHIEK
EN ECONOMIE 12-11-2013.
Economische reflecties bij nieuwe
anticoagulantia voor de behandeling van
DVT en longembolen
Dr. Veerle Ringoet
Coagulation cascade
2012 ACCP guidelines:
recommended agents for VTEx
Phases of anticoagulation
Initial
Long-term
Extended
Recommended anticoagulants
0 to ~7 days
Therapeutic
UFH, LMWH,
fondaparinux or
rivaroxaban
Up to 3 months
VKA (INR2.0-3.0)
or LMWH, dabigatran or rivaroxaban
Kearon C et al. Chest 2012
>3 months to indefinite with
periodic (eg. annual) risk assessment
VKA (INR2.0-3.0)
or LMWH, dabigatran or rivaroxaban
Traditional anticoagulants:
drawbacks
• UFH1
– Parenteral administration IV
– Monitoring and dose
adjustment required
– Risk of HIT
• Oral VKAs2
– Narrow therapeutic window
– Interaction with food and drugs
– Frequent monitoring and
dose adjustment required
• LMWH1
– Parenteral administration s.c.
– Weight-adjusted dosing
– (HIT)
1. Hirsh J et al. Chest 2008;133;141S–159S; 2. Ansell J et al. Chest 2008;133;160S–198S
“New
anticoagulants:
NOAC’s”
Direct Factor Xa inhibitors
Thrombin inhibitors
VII
TF VIIa
Initiation
IX
X
Propagation
IXa
Xa
Inactive factor
Active factor
Transformation
Catalysis
Direct Factor Xa
inhibition
II
Rivaroxaban
Apixaban
Edoxaban
Betrixaban
Darexaban
Clot formation
IIa
Fibrinogen
Adapted from Spyropoulos AC. Expert Opin Investig Drugs 2007;16:431–440
Prothrombin
Thrombin
inhibitors
Dabigatran
(Argotraban)
Fibrin
Rivaroxaban EINSTEIN phase
III: Trial designs
Rivaroxaban
15 mg bid
20 mg od
R
Confirmed acute
symptomatic PE
with or without
symptomatic
DVT
Confirmed
symptomatic
DVT or PE
completing 6
or 12 months
of rivaroxaban
or VKA
N=4,845
Enoxaparin 1.0 mg/kg bid for at least 5 days, followed
by VKA to start ≤48 hours, target INR range 2.0–3.0
Day 1
N=1,197
Day 21
EINSTEIN Extension1 (superiority study)
Treatment period of 6 or 12 months
Rivaroxaban 20 mg od
R
Placebo
Day 1
1. The EINSTEIN Investigators. N Engl J Med 2010; 2. The EINSTEIN–PE Investigators. N Engl J Med 2012
30-day observation after
treatment cessation
Rivaroxaban
N=3,449
30-day observation after
treatment cessation
Confirmed
acute
symptomatic
DVT without
symptomatic
PE
EINSTEIN DVT1 and EINSTEIN PE2 (non-inferiority studies)
Treatment period of 3, 6 or 12 months
EINSTEIN DVT and PE:
exclusion criteria
•
•
•
•
•
•
Thrombectomy, insertion of a caval
filter or use of a fibrinolytic agent to
treat current DVT and/or PE
Indication for VKA other than DVT
and/or PE
>48 hours prerandomization treatment
with therapeutic dosages of
anticoagulant treatment or more than a
single dose of VKA prior to
randomization
Creatinine clearance <30 ml/min
Significant liver disease or ALT
>3× ULN
Life expectancy <3 months
•
•
•
•
•
•
Active bleeding or high risk for bleeding
Systolic blood pressure >180 mm Hg
or diastolic blood pressure
>110 mm Hg
Childbearing potential without proper
contraceptive measures, pregnancy or
breast feeding
Bacterial endocarditis
Participation in another
pharmacotherapeutic study within
30 days before screening
Concomitant use of strong CYP3A4
inhibitors or inducers
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510; The EINSTEIN–PE
Investigators. N Engl J Med 2012; 366:1287-1297; EINSTEIN Integrated Protocol/Study
number 11702/Version no 2.0/08Jun2009, incl. Amend 2, 3, 4
EINSTEIN DVT and PE: study
outcomes
Primary efficacy outcome*
• Symptomatic recurrent VTE: composite of
recurrent DVT, nonfatal PE or fatal PE
Principal safety outcome*
• Combination of major and non-major
clinically relevant bleeding
*Adjudicated by a central independent and blinded adjudication committee
1. The EINSTEIN Investigators, N Engl J Med 2010;363:2499–2510;
2. The EINSTEIN–PE Investigators. N Engl J Med 2012; 366:1287-1297
EINSTEIN DVT: primary efficacy
outcome analysis
Rivaroxaban
(n=1,731)
First symptomatic recurrent VTE
Recurrent DVT
Recurrent DVT + PE
Non-fatal PE
Fatal PE/unexplained death where
PE cannot be ruled out
0.44
0.68
0
Enoxaparin/VKA
(n=1,718)
n
36
14
1
20
(%)
(2.1)
(0.8)
(<0.1)
(1.2)
n
51
28
0
18
(%)
(3.0)
(1.6)
(0.0)
(1.0)
4
(0.2)
6
(0.3)
1.04
1.00
HR
2.00
Rivaroxaban
superior
p=0.08 for superiority (two-sided)
Rivaroxaban
non-inferior
p<0.001 for non-inferiority
(one-sided)
ITT population
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
Rivaroxaban
inferior
EINSTEIN DVT: principal safety
outcome analysis
Rivaroxaban
(n=1,718)
Enoxaparin/VKA
(n=1,711)
HR (95% CI)
n
(%)
n
(%)
p-value
139
(8.1)
138
(8.1)
0.97 (0.76–1.22)
p=0.77
14
(0.8)
20
(1.2)
0.65 (0.33–1.30)
p=0.21
Contributing to death
1
(<0.1)
5
(0.3)
In a critical site
3
(0.2)
3
(0.2)
10
(0.6)
12
(0.7)
126
(7.3)
119
(7.0)
First major or non-major clinically
relevant bleeding
Major bleeding
Associated with fall in haemoglobin
2 g/dl and/or transfusion of 2 units
Non-major clinically relevant bleeding
Safety population
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
EINSTEIN DVT: Key secondary
and other outcomes
Rivaroxaban
Outcome
n/N
(%)
Enoxaparin/VKA
n/N
(%)
HR
(95% CI)
0.67
(0.47–0.95)
Net clinical benefit:
(primary efficacy
outcome plus major
bleeding)
51/1,731
(2.9)
73/1,718
(4.2)
Total mortality
38/1,731
(2.2)
49/1,718
(2.9)
0.67
(0.44–1.02)
Cardiovascular
events
12/1,718
(0.7)
14/1,711
(0.8)
0.79
(0.36–1.71)
The EINSTEIN Investigators. N Engl J Med 2010 (Supplementary Appendix)
p=0.03
EINSTEIN PE:
Primary efficacy outcome analysis
Rivaroxaban
(N=2419)
First symptomatic recurrent VTE
Recurrent DVT
Recurrent DVT + PE
Non-fatal PE
Fatal PE/unexplained death where
PE cannot be ruled out
0.75
0
Enoxaparin/VKA
(N=2413)
n
(%)
n
(%)
50
18
0
22
(2.1)
(0.7)
(0.9)
44
17
2
19
(1.8)
(0.7)
(<0.1)
(0.8)
10
(0.4)
6
(0.2)
1.12
1.69
1.00
2.00
Rivaroxaban
superior
Rivaroxaban
non-inferior
p=0.57 for superiority
(two-sided)
p<0.0026 for non-inferiority
(one-sided)
ITT population
The EINSTEIN–PE Investigators. N Engl J Med 2012; 366:1287-1297
Rivaroxaban
inferior
Primary efficacy outcome:
time to first event
Cumulative event rate (%)
3.0
Rivaroxaban
N=2419
2.5
2.0
Enoxaparin/VKA
N=2413
1.5
1.0
HR=1.12; p<0.0026 (non-inferiority)
0.5
0.0
0
30
60
90
120
150
180
210
240
270
300
330
360
Time to event (days)
Number of patients at risk
Rivaroxaban
2419 2350
2321
2303
2180
2167
2063
837
794
785
757
725
672
Enoxaparin/VKA
2413 2316
2296
2274
2157
2149
2053
837
789
774
748
724
677
ITT population
The EINSTEIN–PE Investigators. N Engl J Med 2012; 366:1287-1297
Principal safety outcome analysis:
major or non-major clinically relevant bleeding
Rivaroxaban
(N=2412)
n
First major or non-major
clinically relevant bleeding
event
(%)
Enoxaparin/VKA
(N=2405)
n
(%)
HR (95% CI)
p-value
249
(10.3)
274
(11.4)
0.90 (0.76–1.07)
p=0.23
26
(1.1)
52
(2.2)
0.49 (0.31–0.80)
p=0.0032
Contributing to death
2
(<0.1)
3
(0.1)
In a critical site
6
(0.2)
27
(1.1)
18
(0.7)
26
(1.1)
228
(9.5)
235
(9.8)
Major bleeding
Associated with fall in
haemoglobin 2 g/dl and/or
transfusion of 2 units
Non-major clinically relevant
bleeding
Safety population
The EINSTEIN–PE Investigators. N Engl J Med 2012; 366:1287-1297
Key secondary and other
outcomes
Rivaroxaban
Enoxaparin/VKA
n/N
(%)
n/N
(%)
HR
(95% CI)
Net clinical benefit*
83/2419
(3.4)
96/2413
(4.0)
0.85 (0.63–1.14)
Total mortality
58/2419
(2.4)
50/2413
(2.1)
1.13 (0.77–1.65)
On-treatment CV events
35/2412
(1.5)
37/2405
(1.5)
0.94 (0.59–1.49)
Stroke/TIA
12/2412
(0.5)
13/2405
(0.5)
MI/UA
15/2412
(0.6)
21/2405
(0.9)
Other
8/2412
(0.3)
3/2405
(0.1)
Stroke/TIA
2/2206
(<0.1)
1/2197
(<0.1)
MI/UA
3/2206
(0.1)
2/2197
(<0.1)
Other
4/2206
(0.2)
0/2197
Outcome
Off-treatment CV events#
*Primary efficacy outcome plus major bleeding
#30-day follow-up
Recurrent VTE and bleeding in fragile
and nonfragile patients
Fragile*
Non-fragile
HR
(95% CI)
n/n
(%)
n/n
(%)
Recurrent VTE
31/987
(3.1)
63/3845
(1.6)
1.97
(1.28–3.04)
Major bleeding
31/984
(3.2)
47/3833
(1.2)
2.72
(1.72–4.29)
144/984 (14.6) 379/3833
(9.9)
1.62
(1.34–1.97)
Clinically relevant
bleeding
*Fragile patients defined as age >75 years, weight ≤50 kg
and/or creatinine clearance <50 ml/min
Recurrent VTE and bleeding in
fragile patients
Rivaroxaban
Enoxaparin/VKA
HR
95% CI
n
(%)
n
(%)
Recurrent VTE
14/510
(2.8)
17/477
(3.6)
0.75 (0.37–1.52)
Major bleeding
7/508
(1.4)
24/476
(5.0)
0.26
64/508 (12.6)
80/476
(16.8)
0.72 (0.52–0.99)
Clinically relevant
bleeding
(0.11–0.61)
Conclusion
• There is no evidence to support a rivaroxaban dose adjustment in
fragile patients
EINSTEIN Extension: study
objective
Primary objective
• Is rivaroxaban superior to placebo in the
long-term prevention of recurrent
symptomatic VTE in patients with
symptomatic DVT or PE who completed
6 or 12 months of treatment with a VKA or
rivaroxaban ?
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
EINSTEIN Extension: study
design
Randomized, double-blind, placebo-controlled, event-driven (n=30),
superiority study
Confirmed
symptomatic
DVT or PE
completing
6 or 12 months
of VKA
Treatment period of 6 or 12 months
Day 1
~53%
Rivaroxaban 20 mg od
N=1,197
R
Placebo
~47%
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
30-day
observation
period
Confirmed
symptomatic
DVT or PE
completing
6 or 12
months of
rivaroxaban or
VKA in
EINSTEIN VTE
programme
EINSTEIN Extension: primary efficacy
outcome and individual components
Rivaroxaban
(n=602)
Placebo
(n=594)
n
(%)
n
(%)
8
(1.3)#
42
(7.1)
Recurrent DVT
5
(0.8)
31
(5.2)
Non-fatal PE
2
(0.3)
13
(2.2)
Fatal PE
0
(0)
1
(0.2)
Unexplained death
(where PE cannot be excluded)
1
(0.2)
0
(0)
Symptomatic recurrent VTE*
ITT population; *Some patients experienced more than one event; #p<0.001
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
EINSTEIN Extension: major bleeding
Rivaroxaban
(n=598)
Placebo
(n=590)
n
(%)
n
(%)
4
(0.7)*
0
(0)
Bleeding contributing to death
0
(0)
0
(0)
Bleeding in a critical site
0
(0)
0
(0)
Associated with fall in haemoglobin
2 g/dl and/or transfusion of 2 units
4
(0.7)
0
(0)
Gastrointestinal bleeding
3
(0.5)
0
(0)
Menorrhagia
1
(0.2)
0
(0)
Major bleeding
Safety population; *p=0.11
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
EINSTEIN Extension: non-major
clinically relevant bleeding
Rivaroxaban
(n=598)
Placebo
(n=590)
n
(%)
n
(%)
32
(5.4)
7
(1.2)
12
(2.0)
2
(0.3)
Nasal
8
(1.3)
1
(0.2)
Rectal/anal
6
(1.0)
2
(0.3)
Skin
4
(0.7)
2
(0.3)
Ear
1
(0.2)
0
(0)
Gastrointestinal
1
(0.2)
0
(0)
Surgical site
1
(0.2)
0
(0)
Non-major clinically relevant bleeding
Urogenital/uterus
Safety population; some patients experienced more than one event
The EINSTEIN Investigators. N Engl J Med 2010;363:2499–2510
Summary and conclusion of the
EINSTEIN study program
 EINSTEIN DVT and PE: rivaroxaban vs standard therapy showed:1,2
 Non-inferiority for efficacy
 Similar findings for the principal safety outcome
 EINSTEIN DVT: rivaroxaban vs standard therapy showed:1

Favourable prespecified net clinical benefit
 EINSTEIN PE: rivaroxaban vs standard therapy showed:2
 Superiority for major bleeding
 EINSTEIN Extension study: rivaroxaban showed:1
– 82% RRR in the recurrence of VTE
– Low incidence of major bleeding ; modest increase in non-major clinically
relevant bleeding compared with placebo
Oral rivaroxaban provides a simple, single-drug approach
for the acute and continued treatment of DVT and PE
1. The EINSTEIN Investigators. N Engl J Med 2010; 2. The EINSTEIN-PE Investigators. N Engl J Med 2012
EINSTEIN DVT and EINSTEIN PE
pooled analysis: major bleeding
First major bleeding
Cumulative event rate (%)
3.0
2.5
Rivaroxaban
n/N (%)
Enoxaparin/VKA
n/N (%)
HR (95% CI)
p-value
40/4130
(1.0)
72/4116
(1.7)
0.54 (0.37–0.79)
p=0.002
2.0
Enoxaparin/VKA
N=4116
1.5
1.0
Rivaroxaban
N=4130
0.5
0.0
0
30
60
90
120
150
180
210
240
270
300
330
360
Time to event (days)
Number of patients at risk
Rivaroxaban
4130
3921
3862
3611
3479
3433
2074
1135
1095
1025
969
947
499
Enoxaparin/VKA
4116
3868
3784
3525
3394
3348
1835
1109
1065
990
950
916
409
Safety population
Buller HR, for the EINSTEIN Investigators. ASH, December 2012
EINSTEIN DVT and PE pooled
analysis: conclusions
 In acute symptomatic DVT and/or PE, rivaroxaban
showed:
 Non-inferiority versus enoxaparin/VKA for efficacy
 Similar incidence rates to enoxaparin/VKA for the principal
safety outcome
 Superiority for major bleeding
 Consistent efficacy and safety results irrespective of age,
body weight, gender, renal function, cancer, and severity of
DVT/PE
 Single-drug approach for treatment of acute DVT,
PE and secondary prevention
CONCLUSIONS RIVAROXABAN
Advantages:
-Fixed dose
-No laboratory monitoring
-Einstein studies , many pts
-Short half-life
 stop 24-48 hrs before surgery
CONCLUSIONS RIVAROXABAN
Drawbacks:
-No long term experience
-Limited duration of treatment
(reimbursement)( max.12 months)
-Insufficient data in cancer pts
-Surgical intervention: stop 24-48 hrs
-Einstein-DVT/PE :
* open-label design
* absolute benefits small
CONCLUSIONS RIVAROXABAN
Contra-indications:
-Renal insufficiency ( cr. cl. ≤ 30
mL/’)
-Significant hepatic impairment
-Pregnancy
No ( not yet…) specific antidote
But: *short half-life 5-9 hrs
*Activated or unactivated
protein concentrate may be
effective
APIXABAN
•
•
•
•
Direct Xa inhibitor
Prevention DVT knee-/hip prosthesis
ADVANCE 2 ( knee) and 3 ( hip)
Versus enoxaparine s.c. 40 mg:
– Combined endpoint prevention VTE, non-fatal
PE, & death:
– RR 0,62 , NNT11 ( knee)
– RR 0,36 , NNT 40 ( hip)
• Safety: no significant difference
DIRECT THROMBIN
INACTIVATOR
DABIGATRAN
•
•
•
•
•
•
Oral direct thrombin inactivator
Can inactivate fibrin-bound thrombin
High affinity and specificity
Prodrug  ( liver) drug
80 % renal excretion
Half-life 12-14 hrs ( longer in elderly,↓renal
function)
• No monitoring
• Surgical intervention: stop Dabi 24-48 hrs ( if
creat clear < 50 mL/’: 48-72 hrs).
DABIGATRAN
• Drawbacks:
– Dose reduction :* > 75-80 yrs
* moderate/severe renal impairment
– Low body weight ? Morbidly obese ?
– No monitoring
– Interactions
• Interactions:
– Food: no
– CYP 450: no
– Substrate for efflux transporter P-glycoprotein drug
interactions !
Inhibitors of P-gp efflux transporter 
Increased dabigatran concentration :
Abiraterone, alfentanil, amiodarone,
atorvastatin, azithromycin•, boceprevir•,
carvedilol, clarithromycin, cobicistat
containing coformulations, conivaptan•,
crizotinib, cyclosporine, darunavir,
diltiazem•, dipyridamole, dronedarone,
duloxetine•, erythromycin, fenofibrate•,
grapefruit and grapefruit juice¥, indinavir•,
itraconazole, ivacaftor, ketoconazole,
lapatinib, lomitapide, lopinavir, lovastatin•,
mefloquine, mifepristone•, nelfinavir,
nicardipine, nifedipine•, nilotinib,
posaconazole•, progesterone,
propafenone•, propranolol, quinidine,
quinine•, ranolazine, reserpine, ritonavir,
ritonavir containing coformulations,
saquinavir, sunitinib, tacrolimus, tamoxifen,
telaprevir, telithromycin•, ticagrelor•,
tolvaptan•, ulipristal, vandetanib,
vemurafenib, verapamil
Inducers of P-gp efflux transporter
Decreased dabigatran concentration
(significant effect) :
Carbamazepine, dexamethasone,
doxorubicin, nefazodone, pentobarbital•,
phenobarbital•, prazosin, rifampin◊, St.
John's wort, tenofovir§, tipranavir,
trazodone, vinblastine.
Antacids 
Decreased dabigatran concentration
(moderate effect) :
H2 antagonists, PPIs
DABIGATRAN
• Contra-indications:
– Renal insufficiency : kreat clear ≤ 30 mL/’
– Pregnancy
– Avoid rifampicin, amiodarone, quinidin,
ketoconazole,clarithromycin…
DABIGATRAN
• If bleeding:
– Stop dabigatran
– Dialysis
– Activated coal ( if ingestion ≤ 2 hrs)
– If life threatening: prothrombin complex concentrate,
recombinant human factor VIIa
– Antidote : aDabi-Fab
DABIGATRAN
• Dabigatran versus warfarin in the treatment of
acute venous thromboembolism. Schulman S,
Kearon C, Kakkar AK, et al. RE-COVER Study
Group . N Engl J Med. 2009;361(24):2342.
• Double blind RCT , non-inferiority, n=2539 pts
• Parenteral antico mean 9 d,then:
dabigatran
warfarin INR 2-3
DABIGATRAN
WARFA
DABI
HR
P
Recurrent venous
thromboembolism
2,1%
2,4%
1,1
<0,001
Major bleeding
1,9%
1,6%
0,82
Any bleeding
21,9%
16,1%
0,71
Discontinuation drug
6,8%
9%
0,05
DABIGATRAN
• Dabigatran versus warfarin in the treatment of acute venous
thromboembolism. Schulman S, Kearon C, et al RE-COVER Study
Group .
• Conclusion:
– Fixed dose dabigatran as effective as
warfarin
– Similar safety profile
– No laboratory monitoring
DABIGATRAN
• N Engl J Med. 2013 Feb 21;368(8):709-18.
Extended use of dabigatran, warfarin, or placebo
in venous thromboembolism.
Schulman S, Kearon C, Kakkar AK, et al.;
RE-MEDY Trial Investigators;
RE-SONATE Trial Investigators.
• Double blind RCT , pts completed ≥ 3 months of
therapy; then active control study ( dabigatran vs
warfarin) / placebo control study ( dabigatran vs
placebo)
RE-MEDY & RE-SONATE trials
DABI
WAR
HR
P
Recurrent venous
thromboembolism
1,8 %
1,3 %
1,44
0,01
Major bleeding
0,9 %
1,8 %
0,52
ACS
0,9 %
0,2 %
0,02
DABI
PLAC HR
P
0,4 %
5,6 %
Recurrent
thromboembolism
0,08
COST/1day treatment
Warfarin=Marevan®:
1 co/d=0,24 €; 0,25 co/d=0,06 €
Enoxaparin=Clexane:
2x80mg/d=10,3€/d;2x120mg/d=15,8€
Apixaban=Eliquis®:
(Prophylactic dose) 2x2,5mg/d=2,88 €/d
Rivaroxaban=Xarelto®:
2x15 mg/d= 5,1 €/d
1x20 mg/d=2,54 €/d
Dabigatran=Pradaxa®:
2x110 or 2x150 mg/d=2,67 €/d
But:
Warfarin:
-cost INR
-consultation physician
-blood drawing
-Costs ( major ) bleeding
LMWH:
-cost nurse
-cost hospitalisation ( acute
PE/DVT)
TERUGBETALING BELGIE
11/2013
• Eliquis®:
– Cat Bf: preventie CVA bij non-valvulaire VKF + ≥1
risicofactor
– Preventief na heup-en knievervangende OP
• Pradaxa®:
– Preventie CVA bij non-valvulaire VKF + ≥1 risicofactor
– Preventief na heup-en knievervangende OP
• Xarelto® :
– preventie CVA bij non-valvulaire VKF + ≥1 risicofactor
– Behandeling DVT, preventie recidief DVT/PE na acute
DVT
– Preventie VTE bij orthopedische chirurgie heup/knie
II - Elementen te bevestigen door de behandelende arts:
Ik ondergetekende, behandelende arts, verklaar dat de bovenvermelde volwassen
patiënt met DVT (diep veneuze trombose) een
behandeling nodig heeft met Xarelto 15 mg 2 maal daags gedurende de eerste 3
weken voor de initiatie (2 per dag
gedurende 3 weken), gevolgd door eenmaal daags Xarelto 15 mg of Xarelto 20
mg gedurende de voortgezette behandeling
van diep veneuze trombose (DVT) en preventie van recidief DVT en pulmonale
embolie (PE) na een acute DVT.
De duur van de vergoeding hangt samen met de behoeften van de behandeling
per DVT, namelijk een korte behandelingsduur
van maximaal 3 maanden na voordoen van risicofactoren van voorbijgaande aard
en een langere behandelduur (6 tot
12 maanden) gebaseerd op permanente risicofactoren of idiopathische DVT.
Datum van DVT: / /
De specialiteit zal worden toegediend met een dosis van tweemaal daags 15 mg
gedurende de eerste drie
weken, gevolgd door eenmaal daags 20 mg erna.
Staatsblad 21/08/2013.
BIJ WIE NOAC’s ?
• Wel:
–
–
–
–
Bijwerkingen op VKA
Contra-indicatie VKA
Geneesmiddeleninteracties
Problematische INR controles
• Niét :
– ptn zonder VKA problemen
– Contra-indicaties NOAC
MELDEN BIJWERKINGEN
BELGIE 11/2013
• BCGH:
-Papieren gele fiche FAGG
-www.gelefiche.be
[email protected]
• Eliquis®
-Bristol-Myers Squibb:
-email:safety [email protected]
-tel 023527172
MELDEN BIJWERKINGEN
BELGIE 11/2013
• Pradaxa® :
-Boehringer Ingelheim
-email:pv local [email protected]
-tel. 027733438
• Xarelto®
-Bayer
-email:[email protected]
-tel 025356393