Interaction between paracetamol and warfarin in patients: a double
Download
Report
Transcript Interaction between paracetamol and warfarin in patients: a double
INTERACTION BETWEEN
PARACETAMOL AND
WARFARIN IN PATIENTS: A
DOUBLE-BLIND, PLACEBO-
CONTROLLED, RANDOMIZED
STUDY
นสภ. มารุตต์ ตรีอน
ิ ทอง
รหัส 47210463
นสภ. ชฎาพร พรมปั ญญา รหัส 47230007
ี งรายประชานุเคราะห์
แหล่งฝึ ก : โรงพยาบาลเชย
OBJECTIVE
Main
assess the effect of paracetamol
on the INR in patients receiving a
stable regimen of warfarin
OBJECTIVE
Secondary
+investigate the mechanism
+evaluate a correlation between INR
variation and paracetamol intake
+determine a min. duration of
paracetamol administration which does not
cause significant INR variations
+identify early variations in clotting
factor activities
PATIENTS
20
outpatients, both sex, 18+ years
Target INR 2-3
On stable warfarin > 1 m (2-9
mg/day)
No recent or ongoing diseases
The intake of concomitant Tx as well
as medication known to affect INR
values allowed on condition that
dosages were kept constant
throughout the trial
STUDY DESIGN
Single-center, double-blind,placebocontrolled, randomized and crossover study
20 pts
10: placebo
14 d
10: paracetamol 4 g*
14 d
Wash-out period
14 d
Paracetamol 4 g
14 d
*Doliprane®, 500 mg capsule
Placebo
14 d
STUDY DESIGN (CONT.)
Run-in period
Verify stability anticoagulant treatment
D 0 (before 1st
medication intake)
Physical examine and blood sample
taken at hospital
D 2, 4, 7, 9, 11 and
14
Visit at home
-examine signs of hemorrhage and thrombosis
-ask about possible lapses from the protocol
Ex. changing any OTC or prescription drugs
-counting the returned empty blister packs and
the unused paracetamol and placebo capsules
-evaluate alcohol consumption and dietary
intake of food containing vit.K
Intra-individual
variability of INR = 0.3
(previous studies) => INR increase > 0.5 was
significant and related to an interaction
between paracetamol and warfarin
If
2 successive INR values were >3.5, warfarin
was to be discontinued then restarted at the
same dose as before
If INR remained outside the target range
during the wash-out period , the warfarin
regimen was readjusted and the pt entered the
2nd study period after stabilization on the new
dose
RESULT
Mean
age: 62±19 years (range 24-89 years)
19 (10 women and 9 men) completed the study
1 pt withdrew her consent for personal reason
after 4 days in the 1st period and 1 pt had a
serious protocol deviation => excluded from final
analysis
No bleeding events
The paracetamol regimen was stop in 4 pts and
1 pt in placebo administration because of
increases in 2 consecutive INR values
RESULT (CONT.)
1
pt had a serious non-drug-related
adverse event (hospitalization for a
sinoatrial block) and discontinued the
trial on day 4 of the 2nd period
RESULT (CONT.)
No
significant variations in INR were
observed during the placebo period
Paracetamol therapy significant rise in
mean INR was observe within 2 day
Continued to increase until day 7 and
remained significant enhanced until the
end of the Tx period
In
each pt, the mean INR peak was
significantly higher in the paracetamol
period than in the placebo period
RESULT (CONT.)
The
mean absolute AUC of factor II,VII and X
chandes from baseline were significantly
greater during the paracetamol period than
during the placebo period
No significant variation in factor V levels
CONCLUTION
Mean
INR rose rapidly after the start of
patacetamol and significantly increase
within 1 week of paracetamol intake
Paracetamol intake were signigicant
reduction in the vitamin K-dependent
clotting factor II, VII, and X
เหตุผลทีไ่ ม่เห็นด้วยก ับ
ข้อมูลด ังกล่าว
ึ ษา
รูปแบบการศก
ึ ษา
จานวนของผู ้ป่ วยในการศก
ขนาดยา
การตรวจติดตาม
้
การประเมินความร่วมมือการใชยาตามส
งั่
ความแปลผันของ
INR
เกณฑ์การค ัดเข้า/ค ัดออก
ึ ษา
จากการศก
ความคงทีข
่ อง
INR
การรับประทานยาอืน
่ ร่วมด ้วย
ึ ษา
ล ักษณะต่างๆ ของกลุม
่ ศก
่ งอายุ
ชว
โรคร่วมอืน
่ ๆ
ยาอืน
่ ๆทีไ่ ด ้รับ/สมุนไพร
Thank You
& Questions