Don’t use two or more medications that are known to increase the risk of bleeding without evaluating the potential risks and benefits. These medications include direct oral anticoagulants, warfarin, aspirin, selective serotonin reuptake inhibitors (SSRIs), antiplatelet agents, NSAIDs, and corticosteroids.

Rationale and Comments

Prescribing more than one of these medications concurrently may result in an enhanced risk of bleeding. This heightened risk of bleeding may be mediated through complex pharmacokinetic and/or pharmacodynamic mechanisms. It is well established that the combination of anticoagulants and NSAIDs increase the risk of bleeding. A combination of warfarin with either single or dual antiplatelet therapy significantly increases the risk of major bleeding by two- to four-fold, respectively. The most commonly prescribed antidepressant therapeutic class (SSRIs), may decrease platelet serotonin uptake, leading to impaired platelet aggregation, and thereby increased risk of bleeding. Specific to gastrointestinal bleeding, SSRIs may also increase gastric acid secretion. Bleeding has been observed in association with other antidepressants in some observational studies; however, recent systematic reviews give weight to SSRIs in combination with NSAIDs for increased vigilance for risk of upper gastrointestinal bleeding. In patients where benefits outweigh the risks of the combination, appropriate education of patient and caregivers and appropriate follow-up monitoring for early detection of any signs and symptoms of bleeding is highly recommended.

Sponsoring Organizations

American Society of Consultant Pharmacists

Sources

Systematic reviews

Disciplines

Gastroenterologic

References

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