Increased Bleeding Risk With Concurrent Use of Selective Serotonin Reuptake Inhibitors and Coumarins

Schalekamp, Tom

doi:10.1001/archinternmed.2007.32

Cited by 127 publications

(89 citation statements)

References 23 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Gschwind

Rollason

Lovis

et al. 2012

Eur J Clin Pharmacol

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Purpose The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. Methods We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding.Results One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. Conclusion Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drugs.

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Section: Discussionmentioning

confidence: 99%

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

Gschwind

Rollason

Lovis

et al. 2012

Eur J Clin Pharmacol

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show abstract

“…[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) .…”

Section: Vka Drug Interactions To Avoidmentioning

confidence: 99%

Evidence-Based Management of Anticoagulant Therapy

Holbrook

Schulman

Witt

et al. 2012

Chest

1,068

353

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“…In a large community‐based observational AF cohort, we previously found an adjusted relative risk for major hemorrhage of 1.41 (95% CI, 1.04–1.92) with the addition of SSRIs to warfarin 26. Several studies using large national databases have reported that concomitant use of SSRIs with vitamin K antagonists increased the risk of hospitalized bleeding events by roughly 30% to 70%, and a recent nested case‐control study from the United Kingdom Clinical Practice Datalink found an odds ratio of 1.73 (95% CI, 0.89–3.39) for intracranial hemorrhage in patients taking warfarin when SSRIs were added 15, 24, 25, 27. Although the CIs overlapped to varying degrees, our point estimate hazard ratio, SSRI versus no‐SSRI, of 1.16 was smaller than those previously reported and close to the null value of 1.0.…”

Section: Discussionmentioning

confidence: 99%

“…Further, SSRIs inhibit the cytochrome P450 metabolic pathway, potentially increasing warfarin's effect 21, 22, 23. Several studies have reported that the combination of warfarin and SSRIs leads to an increased risk of major hemorrhage 24, 25, 26, 27, 28. No study has yet examined the possible drug‐drug interaction between SSRIs and non–vitamin K antagonist oral anticoagulants.…”

Section: Introductionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitors and Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: An Analysis From the ROCKET AF Trial

Quinn

Hellkamp

Hankey

et al. 2018

JAHA

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BackgroundThere is concern that selective serotonin reuptake inhibitors (SSRIs) substantially increase bleeding risk in patients taking anticoagulants.Methods and ResultsWe studied 737 patients taking SSRIs in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Embolism and Stroke Trial in Atrial Fibrillation) trial of rivaroxaban compared with warfarin for the prevention of stroke/systemic embolism in patients with atrial fibrillation. These patients were propensity score matched 1:1 to 737 patients not taking SSRIs. The primary outcome measure was major and nonmajor clinically relevant bleeding events, the principal safety outcome in ROCKET AF. Over a mean 1.6 years of follow‐up, the rate of major/nonmajor clinically relevant bleeding was 18.57 events/100 patient‐years for SSRI users versus 16.84 events/100 patient‐years for matched comparators, adjusted hazard ratio (aHR) of 1.16 (95% confidence interval [CI], 0.95–1.43). The aHRs were similar in patients taking rivaroxaban (aHR 1.11 [95% CI, 0.82–1.51]) and those taking warfarin (aHR 1.21 [95% CI, 0.91–1.60]). For the rarer outcome of major bleeding, the aHR for SSRI users versus those not taking SSRIs was 1.13 (95% CI, 0.62–2.06) for rivaroxaban; for warfarin, the aHR was higher, at 1.58 (95% CI, 0.96–2.60) but not statistically significantly elevated.ConclusionsWe found no significant increase in bleeding risk when SSRIs were combined with anticoagulant therapy, although there was a suggestion of increased bleeding risk with SSRIs added to warfarin. While physicians should be vigilant regarding bleeding risk, our results provide reassurance that SSRIs can be safely added to anticoagulants in patients with atrial fibrillation.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00403767.

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Increased Bleeding Risk With Concurrent Use of Selective Serotonin Reuptake Inhibitors and Coumarins

Abstract: In users of coumarins, SSRI usage was associated with increased risk of hospitalization because of nongastrointestinal bleeding but not because of gastrointestinal bleeding.

Cited by 127 publications

References 23 publications

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

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

Evidence-Based Management of Anticoagulant Therapy

Selective Serotonin Reuptake Inhibitors and Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: An Analysis From the ROCKET AF Trial

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