The effect of drug interactions on bleeding risk associated with warfarin therapy in hospitalized patients

Abstract

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.

Identification and weighting of the most critical “real-life” drug–drug interactions with acenocoumarol in a tertiary care hospital

“…The adjusted odds ratio (OR) for bleeding was highest for CYP2C9 inhibitors (OR 3.6, 95 % CI 2.4-5.6), while NSAIDs, coxibs and SSRIs were also associated with a significant bleeding risk (OR 2.6, 95 % CI 1.6-4.2; OR 3.1, 95 % CI 1.4-6.7; OR 2.6, 95 % CI 1.5-4.3, respectively). The OR for the platelet aggregation inhibitor group was 1.6 (95 % CI 0.8-3.1) [15].…”

“…This mechanism has not been clearly explained, but recent epidemiological data have demonstrated that SSRIs could significantly increase the risk of gastro-intestinal bleeding [46,47]. According to some studies, the use of SSRIs among the population treated with coumarins seems to place patients at an increased risk of bleeding [15,48,49]. A warning should be added to make the physician aware of this interaction.…”

“…tobacco, weight, sex, age and single nucleotide polymorphisms) influence the response to acenocoumarol treatment [5,11]. Drug-drug interactions (DDIs) are an additional factor affecting the variability of anticoagulation and the occurrence of serious ADRs [4,[12][13][14][15]. These DDIs are well described in the literature, but their respective importance in clinical practice is difficult to determine, especially those involving acenocoumarol since most of the studies published to date have focused on warfarin.…”

Evidence-Based Management of Anticoagulant Therapy

“…For nonselective NSAIDs, studies reported ORs or risk ratios (RRs) from 1.9 (95% CI, 1.4-3.7) to 4.6 (95% CI, 3.3-6.5). [100][101][102][103]105,118 In addition, two studies reported a higher risk of bleeding with nonselective NSAIDs compared with COX-2-selective NSAIDs. 101,104 There was less consistency in the relationship between COX-2-selective NSAIDs plus VKAs vs VKA alone and bleeding outcomes, varying from a nonsignifi cant RR of 1.4 (95% CI, 0.44-4.30) to a signifi cant OR of 3.1 (95% CI, 1.4-6.7).…”

“…[112][113][114] Similarly, some studies suggest that selective serotonin reuptake inhibitors, tramadol, acetaminophen, coenzyme Q, and ginger may increase the risk of bleeding, but these also require confi rmation. 103,105,106,116,117 Recommendations 3.8. For patients taking VKAs, we suggest avoiding concomitant treatment with NSAIDs, including COX-2-selective NSAIDs, and certain antibiotics (Grade 2C) .…”