No clinically relevant drug interaction between paracetamol and phenprocoumon based on a pharmacoepidemiological cohort study in medical inpatients.
OBJECTIVE
A recent case control study suggests that paracetamol at a dosage above 1300 mg/day increases the anticoagulant effects of warfarin. In many European countries, phenprocoumon and not warfarin is used as an anticoagulant. However, the effects of paracetamol on the anticoagulant effects of phenprocoumon have so far not been evaluated.


METHODS
This study is based on the data recorded prospectively between 1996 and 1998 in two Swiss teaching hospitals in the pharmacoepidemiological database of the SAS/CHDM project. As a first step, all phenprocoumon-treated patients with at least one international normalized ratio (INR) determination at least 4 days after cohort entry were selected and evaluated concerning paracetamol co-administration. The "paracetamol group" included only patients receiving at least 1300 mg/day paracetamol on the 3 days preceding the INR determination, whereas the comparison group contained only patients without paracetamol exposure during hospital stay. Thereafter, INR values of the paracetamol and the comparison groups were compared.


RESULTS
The paracetamol and the comparison groups included 54 and 180 patients, respectively. Patients' characteristics in both groups were comparable. Patients in the paracetamol group received on average 2220 +/- 651 mg/day paracetamol. The median duration of paracetamol exposure was 5 days. The median difference in INR values between the paracetamol and the comparison groups was -0.3 (with a 99% confidence interval of -0.6, 0.1).


CONCLUSIONS
These results suggest that paracetamol co-administration at a dosage of 2000-2500 mg/day for 3 days has no clinically relevant effects on the anticoagulant effects of phenprocoumon.
Fattinger
Karin
K
Dept. of Medicine, University Hospital, Zurich, Switzerland. fattinge@kpt.unizh.ch
Frisullo
Roberto
R
Masche
Urspeter
U
Braunschweig
Suzanne
S
Meier
Peter J
PJ
Roos
Malgorzata
M
D000082:Acetaminophen / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000494:pharmacology*
D000925:Anticoagulants; D000082:Acetaminophen; D010644:Phenprocoumon