The effect of drug interactions on bleeding risk associated with warfarin therapy in hospitalized patients.
BACKGROUND
Bleeding is a serious adverse drug reaction associated with warfarin therapy, often induced by interacting co-medication.


METHODS
We investigated the frequency and clinical consequences of warfarin drug interactions utilizing medical records of 6,772 warfarin-treated in-patients of Turku University Hospital.


RESULTS
A total of 48% of warfarin-treated in-patients were exposed to interacting co-medication. Adjusted odds ratio (OR) for bleeding was highest for cytochrome P450 2C9 (CYP2C9) inhibitors (OR 3.6; 95% confidence interval (CI) 2.4-5.6). Non-selective non-steroidal anti-inflammatory drugs (NSAID) and coxibs were associated with a bleeding risk of a similar magnitude (OR 2.6; 95% CI 1.6-4.2 and OR 3.1; 95% CI 1.4-6.7, respectively). Selective serotonin re-uptake inhibitors (SSRI) were associated with a remarkably higher bleeding risk than non-SSRIs (OR 2.6; 95% CI 1.5-4.3 and OR 1.2; 95% CI 0.3-4.3, respectively). Odds ratio for bleeding in the platelet aggregation inhibitor group was 1.6 (95% CI 0.8-3.1).


CONCLUSIONS
We conclude that co-medication in warfarin-treated in-patients is common and should be carefully evaluated to decrease the bleeding risk associated with warfarin therapy.
Hauta-Aho
Milka
M
Department of Pharmacology, Drug Development, and Therapeutics, University of Turku, Turku, Finland. mehaah@utu.fi
Tirkkonen
Tuire
T
Vahlberg
Tero
T
Laine
Kari
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D000925:Anticoagulants / Q000009:adverse effects* / Q000493:pharmacokinetics; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D016022:Case-Control Studies; D065729:Cytochrome P-450 CYP2C9; D016208:Databases, Factual; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D005387:Finland; D006470:Hemorrhage / Q000139:chemically induced*; D006760:Hospitalization; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D014859:Warfarin / Q000009:adverse effects* / Q000493:pharmacokinetics; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases