Apixaban with Vortioxetine Interaction Details

Brand Names Associated with Apixaban

Brand Names Associated with Vortioxetine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

An increased risk of bleeding

Interaction Summary

Vortioxetine, a serotonin reuptake inhibitor, may increase the risk of bleeding events when coadministered with aspirin, warfarin, or other anticoagulants. SSRI use with antiplatelet agents may increase the risk of bleeding events[1][2]. The release of serotonin by platelets is important for maintaining hemostasis. Reports of bleeding events associated with inhibition of serotonin reuptake have included ecchymosis, hematoma, epistaxis, petechiae, and live-threatening hemorrhages. Although coadministration of vortioxetine and either warfarin or aspirin demonstrated no significant pharmacokinetic effects during drug interaction studies, concomitant use of vortioxetine with other agents that affect coagulation or bleeding may increase the risk of bleeding. Carefully monitor patients when vortioxetine is initiated or discontinued in patients receiving drugs that interfere with hemostasis. Inform patients of the increased risk of bleeding associated with the concomitant use of vortioxetine with antiplatelet and anticoagulants agents. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing vortioxetine [3].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of vortioxetine with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding. Carefully monitor patients when vortioxetine is initiated or discontinued in patients receiving drugs that interfere with hemostasis. Inform patients of the increased risk of bleeding associated with the concomitant use of vortioxetine with antiplatelet and anticoagulants agents. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing vortioxetine[3].

Mechanism Of Interaction

Release of serotonin by platelets; additive effects on hemostasis

Literature Reports

A) In a retrospective study of patients over 50 years of age with the diagnosis of acute myocardial infarction (N=27,058), SSRI use with any antiplatelet therapy significantly increased the risk of bleeding by 1.42-fold compared with aspirin use alone. Therapy with aspirin, clopidogrel, and an SSRI significantly increased risk by 2.35-fold compared with aspirin use alone and by 1.57-fold compared with clopidogrel and aspirin combination therapy [2].

B) In a systematic review and meta-analysis of 22 observational studies, SSRI use was associated with a significant 1.55 fold increase in risk of upper gastrointestinal bleeding (UGIB). Concomitant use of SSRIs and antiplatelet drugs was associated with a 2.48-fold increase in risk of UGIB (3 studies) [1].

C) Coadministration of multiple daily doses of vortioxetine and warfarin 1 to 10 mg/day did not result in significant effects on prothrombin values, INR, or total warfarin pharmacokinetics (both R- and S-warfarin). Similarly, coadministration of multiple daily doses of vortioxetine and aspirin 150 mg/day did not result in significant effects on platelet aggregation or pharmacokinetics of aspirin or salicylic acid [3].

D) Case-control and cohort studies have shown that the combined use of selective serotonin and norepinephrine reuptake inhibitors (such as vortioxetine) and antiplatelet agents has been associated with an increased risk of gastrointestinal bleeding. Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage. Bleeding events reported have included epistaxis, ecchymosis, hematoma, petechiae, and life-threatening hemorrhages [3].

References

1 ) Jiang HY, Chen HZ, Hu XJ, et al: Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2015; 13(1):42-50.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

2 ) Labos C, Dasgupta K, Nedjar H, et al: Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ 2011; 183(16):1835-1843.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

3 ) Product Information: TRINTELLIX oral tablets, vortioxetine oral tablets. Takeda Pharmaceuticals America Inc (per FDA), Lexington, MA, 2023.

Apixaban Overview

• Apixaban is used help prevent strokes or blood clots in people who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body and possibly causing strokes) that is not caused by heart valve disease. Apixaban is also used to prevent deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in people who are having hip replacement or knee replacement surgery. Apixaban is also used to treat DVT and PE and may be continued to prevent DVT and PE from happening again after the initial treatment is completed. Apixaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

Vortioxetine Overview

• Vortioxetine is used to treat depression in adults. Vortioxetine is in a class of medications called serotonin modulators. It works mainly by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.