Warfarin with Fluoxetine Interaction Details

Brand Names Associated with Warfarin

Brand Names Associated with Fluoxetine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

An increased risk of bleeding

Interaction Summary

Concomitant use of FLUoxetine and warfarin may result in an increased INR. Case-control and cohort studies have shown that the combined use of SSRIs, including FLUoxetine, and anticoagulants, including warfarin, has been associated with an increased risk of bleeding . Due to this additive effect, closely monitor patients taking warfarin for altered anticoagulant effects, including increased INR and bleeding, when FLUoxetine therapy is initiated or discontinued .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of FLUoxetine and warfarin may result in an increased INR. Coadministration may also result in increased risk of bleeding, as each drug by itself is associated with bleeding. Due to this additive effect, closely monitor patients taking warfarin for altered anticoagulant effects, including increased INR and bleeding, when FLUoxetine therapy is initiated or discontinued .

Mechanism Of Interaction

Release of serotonin by platelets; additive effects on hemostasis

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) 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.

Fluoxetine Overview

• Fluoxetine 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), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works 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.