Warfarin with Sertraline Interaction Details

Brand Names Associated with Warfarin

Brand Names Associated with Sertraline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

An increased risk of bleeding, increased sertraline exposure and an increased risk of sertraline-related adverse events

Interaction Summary

When sertraline and an anticoagulant like warfarin are given concurrently, monitor patient for international normalized ratio (INR) and for signs of increased bleeding. Caution patients about the increased risk of bleeding. Prothrombin time should also be monitored in patients receiving both warfarin and sertraline . The release of serotonin by platelets is important for maintaining hemostasis. Case-control and cohort studies have shown that the combined use of SSRIs (such as sertraline) and anticoagulants has been associated with an increased risk of bleeding . Concomitant use of sertraline with warfarin may potentiate the risk of bleeding. Bleeding events reported have included epistaxis, ecchymosis, hematoma, petechiae, and life-threatening hemorrhages. Also, the concomitant use of sertraline with another drug that is highly bound to plasma protein like warfarin may increase free concentrations of sertraline. Monitor for adverse reactions and reduce dosage of sertraline as warranted .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

When sertraline and an anticoagulant like warfarin are given concurrently, monitor patient for international normalized ratio (INR) and for signs of increased bleeding. Caution patients about the increased risk of bleeding. Also, the concomitant use of sertraline with another drug that is highly bound to plasma protein like warfarin may increase free concentrations of sertraline. Monitor for adverse reactions and reduce dosage of sertraline as warranted.

Mechanism Of Interaction

Release of serotonin by platelets; additive effects on hemostasis; highly bound to plasma protein

Literature Reports

A) According to a retrospective cohort study (n=234), there was an increased risk of clinically relevant bleeding (hospital admission due to bleeding) in patients receiving warfarin for atrial fibrillation during concomitant SSRI therapy or within 2 weeks following SSRI therapy termination. Patients with a mean age of 72 +/- 7 years receiving warfarin plus SSRI (n=117) were matched with randomly selected patients who received warfarin only (n=117). SSRI included FLUoxetine, citalopram, PARoxetine, sertraline, fluvoxaMINE, or escitalopram. Nine patients experienced 11 bleeding episodes during 213.9 treatment years in the warfarin plus SSRI group, and 10 patients experienced 14 bleedings during 586.4 treatment years in the warfarin-only group. The corresponding total incidences of bleedings were 51.4 and 23.9 per 1000 treatment years, respectively. The risk for first bleedings during treatment with warfarin plus SSRI was increased significantly by 3.5 times compared with warfarin only. The SSRI implicated in patients experiencing bleeding at the time of concomitant administration were sertraline or citalopram. The addition of an SSRI was not associated with a change in warfarin dose or INR. The results of the study may be limited by earlier bleeding events, unknown patient adherence, and exclusion of clopidogrel, dipyridamole, corticosteroids and anticoagulants other than warfarin in the model .

B) In 6 reported cases, INR increased during combined FLUoxetine and warfarin therapy. In a seventh case, severe bruising of the lower legs occurred in a woman initially treated with FLUoxetine and, secondarily, started on warfarin .

C) An 83-year-old man died from cerebral hemorrhage secondary to increased warfarin concentrations. The patient had been taking warfarin 30 mg per week for atrial fibrillation with a target INR between 2 and 3. The patient's other drugs included lisinopril, furosemide, potassium, digoxin, and acetaminophen. After being seen for symptoms of depression, anxiety, and insomnia, the patient was given FLUoxetine 20 mg per day and diazePAM 2.5 mg 3 to 4 times per day. Eight days later, the patient's INR increased to 4.8, and the dose of warfarin was decreased to 27.5 mg per week. The patient was later seen for symptoms of drug delirium, including confusion, incoherence, and speaking irrationally. At this point, the INR was 3.64 and FLUoxetine was discontinued. The next day the patient presented to the hospital with left-sided weakness and later died from complications of a large interparenchymal hemorrhage. The authors proposed that the addition of FLUoxetine to the patient's regimen resulted in increased serum levels of both warfarin and diazePAM, resulting in delirium and loss of anticoagulant control .

D) A population-based, case-controlled study of new coumarin users (acenocoumarol and phenprocoumon) with concomitant selective serotonin reuptake inhibitors (SSRIs) resulted in an increased risk of hospitalization due to non-gastrointestinal bleeding. Using national pharmacy and hospitalization records in the Netherlands, researchers identified 1848 cases that were admitted for abnormal bleeding and compared them with 5818 control subjects who were also taking a coumarin. Median duration of treatment in patients was 220 days (range, 1 to 4690 days). Patients on SSRIs showed greater risk for hospitalization for non-gastrointestinal bleeding (adjusted odds ratio (OR) 1.7, 95% confidence interval (CI), 1.1 to 2.5); however, the rate of gastrointestinal bleeding (adjusted OR 0.8, 95% CI, 0.4 to 1.5) was not significantly different .

E) In a non-blinded, randomized, placebo-controlled trial involving 12 healthy volunteers, the effect of sertraline on the plasma protein binding of warfarin was assessed. On days and 32 of the study, all participants received warfarin 0.75 mg/kg. Beginning on day 11, each volunteer was randomized to either the sertraline or placebo group; the sertraline was gradually increased from 50 mg/day to 200 mg/day. Prothrombin time was measured prior to each dose of warfarin and periodically thereafter. The researchers concluded that the anticoagulant effects of warfarin were not enhanced by sertraline to a clinically significant degree, despite the fact that sertraline was given in a higher-than-usual dose .

F) Case reports and epidemiological studies (case-control and cohort studies) have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence 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 related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages .

Warfarin Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

Sertraline Overview

• Sertraline is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks), posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). It is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. Sertraline is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amounts 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.